International Journal Of General Medicine[JOURNAL]
Sun
200 papers
Predictive Value of First-Trimester Serum TREM2 and SIGLEC1 Levels for Adverse Pregnancy Outcomes in Women with PCOS.
Li S, Liu Y, Li W … +3 more , Zhang N, Sun J, Liu H
Int J Gen Med · 2026 · PMID 42369564 · Full text
OBJECTIVE: To investigate the predictive value of first-trimester serum triggering receptor expressed on myeloid cells 2 (TREM2) and sialic acid-binding immunoglobulin-like lectin 1 (SIGLEC1) levels for adverse pregnancy...
OBJECTIVE: To investigate the predictive value of first-trimester serum triggering receptor expressed on myeloid cells 2 (TREM2) and sialic acid-binding immunoglobulin-like lectin 1 (SIGLEC1) levels for adverse pregnancy outcome (APO) in pregnant women with polycystic ovary syndrome (PCOS), and to provide novel biomarkers for risk stratification management during pregnancy. METHODS: This retrospective cohort study enrolled 380 singleton pregnant women with PCOS diagnosed between August 25, 2022, and January 25, 2025. Serum samples collected at gestational weeks 6-12 were retrieved from the biobank. TREM2 and SIGLEC1 concentrations were measured using ELISA. Participants were stratified into APO (n=117) and non-APO (n=263) groups. Receiver operating characteristic (ROC) curve analysis assessed predictive performance, and multivariable logistic regression identified independent risk factors. RESULTS: Comparison of clinical data revealed that serum TREM2 and SIGLEC1 levels in the first trimester were significantly higher in the APO group than in the non-APO group (p < 0.05). Additionally, waist circumference, fasting plasma glucose (FPG), fasting insulin (FINS), and homeostatic model assessment for insulin resistance (HOMA-IR) were all significantly elevated in the APO group compared with the non-APO group (all p < 0.001). ROC analysis showed TREM2 achieved an area under the curve (AUC) of 0.828 (sensitivity 80.23%, specificity 75.21%) and SIGLEC1 yielded an AUC of 0.815 (sensitivity 83.65%, specificity 63.25%). The combined model demonstrated superior predictive accuracy (AUC 0.899, sensitivity 84.79%, specificity 82.05%). Multivariable logistic regression analysis demonstrated that elevated waist circumference (OR = 1.035, 95% CI: 1.010-1.060), HOMA-IR (OR = 2.027, 95% CI: 1.053-3.902), TREM2 (OR = 1.007, 95% CI: 1.005-1.009), and SIGLEC1 (OR = 1.006, 95% CI: 1.004-1.008) were all independent risk factors for APO in pregnant women with PCOS (all p < 0.05). TREM2 and SIGLEC1 levels positively correlated with HOMA-IR (r=0.202 and 0.231, respectively; both p < 0.001). CONCLUSION: Elevated serum TREM2 and SIGLEC1 levels in early pregnancy are associated with overall APO risk in PCOS patients, and their combined detection shows predictive potential; differential predictive values for specific outcome subtypes await further validation.
Mendelian Randomization and Single-Cell RNA Sequencing Reveal CKAP4 and PFDN5 as Tumor Cell-Specific Causal Genes for Glioblastoma.
Huang C, Dong M, Yu Y … +6 more , Wang C, Huang C, Li T, Su X, Shi F, Feng D
Int J Gen Med · 2026 · PMID 42369563 · Full text
BACKGROUND: Glioblastoma (GBM) is an aggressive primary brain tumor with unclear etiology. We aimed to identify causal risk genes by integrating single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR). ME...
BACKGROUND: Glioblastoma (GBM) is an aggressive primary brain tumor with unclear etiology. We aimed to identify causal risk genes by integrating single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR). METHODS: Differentially expressed genes (DEGs) from public databases were overlapped and analyzed via MR to screen for causal genes. A prognostic model was built using these genes and validated through immune infiltration analysis, single-cell mapping, and experimental assays (RT-qPCR, Western blot). RESULTS: A 6-gene prognostic signature (TMEM158, HOXB2, CKAP4, PEPD, PFDN5, NPC2) was established, where higher risk scores correlated with poorer overall survival and distinct immune profiles. scRNA-seq confirmed tumor cell-specific expression, validated experimentally. Multivariate MR highlighted CKAP4 and PFDN5 as having direct causal links to GBM. CONCLUSION: The 6-gene signature predicts GBM prognosis, and CKAP4/PFDN5 are promising causal biomarkers and therapeutic targets. This integrated approach provides novel molecular insights and supports personalized therapy development in GBM.
Albumin-to-Globulin Ratio as a Predictor of Disease Severity in Emergency Department Patients Presenting with Flank Pain.
Untan I, Sabur V
Int J Gen Med · 2026 · PMID 42358764 · Full text
BACKGROUND: Flank pain is a common emergency department (ED) presentation with a wide differential diagnosis. The albumin-to-globulin ratio (AGR) reflects both nutritional status and systemic inflammation, but its utilit...
BACKGROUND: Flank pain is a common emergency department (ED) presentation with a wide differential diagnosis. The albumin-to-globulin ratio (AGR) reflects both nutritional status and systemic inflammation, but its utility in pre-intervention ED patients with flank pain has not been systematically evaluated. METHODS: In this retrospective cross-sectional study, we included 291 consecutive adults who presented to the ED with flank pain and underwent urinary ultrasonography between August 2022 and May 2023. Severe presentation was defined as ≥2 of the following: hydronephrosis, acute kidney injury (creatinine >1.2 mg/dL), elevated CRP (>50 mg/L), or leukocytosis (WBC >12×10/μL). Discriminative performance was assessed by receiver operating characteristic (ROC) analysis. Multivariable logistic regression was performed with adjustment for age, sex, urolithiasis, and log-NLR, deliberately excluding CRP, creatinine, and WBC to avoid incorporation bias. Incremental value beyond routinely available markers was assessed by comparing nested models containing CRP and creatinine, with and without AGR. RESULTS: Among 291 patients (mean age 47.5 ± 23.5 years, 46% male), 59 (20.3%) had severe presentations. AGR was significantly lower in the severe group (1.26 ± 0.35 vs 1.55 ± 0.31, < 0.001), with moderate discriminative ability (AUC 0.729; optimal cutoff ≤1.35; sensitivity 62.7%, specificity 77.2%). In multivariable analysis, AGR remained an independent predictor; each 0.1-unit decrease was associated with 18% higher odds of severe presentation (adjusted OR 1.18, 95% CI 1.04-1.34, = 0.010). However, AGR did not improve discrimination beyond a model containing CRP and creatinine (ΔAUC = 0.000, = 0.957). AGR did not differ between patients with and without urolithiasis ( = 0.14). CONCLUSION: AGR is an independent predictor of severe presentation in ED patients with flank pain, but its moderate sensitivity and absence of incremental value beyond CRP and creatinine suggest it should be used as an adjunctive marker rather than a stand-alone screening tool. Prospective validation is needed before integration into ED triage algorithms.
Admission Uric Acid, Troponin, and C-Reactive Protein Levels and In-Hospital Mortality in Acute Stroke Patients.
Yüceer Ö, Vural A
Int J Gen Med · 2026 · PMID 42344106 · Full text
OBJECTIVE: Stroke remains a leading cause of in-hospital mortality worldwide. Routinely available laboratory biomarkers obtained at emergency department admission may facilitate early risk stratification. This study aime...
OBJECTIVE: Stroke remains a leading cause of in-hospital mortality worldwide. Routinely available laboratory biomarkers obtained at emergency department admission may facilitate early risk stratification. This study aimed to evaluate the associations between admission serum uric acid (SUA), troponin, and C-reactive protein (CRP) levels and in-hospital mortality in patients with acute stroke. METHODS: This retrospective single-center study included 403 adults diagnosed with acute ischemic or hemorrhagic stroke between January 1, 2019, and January 1, 2022. Demographic data, comorbidities, and admission laboratory findings were extracted from electronic hospital records. Univariate and multivariable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Receiver operating characteristic (ROC) analysis was used to evaluate discriminatory performance. RESULTS: Of 403 patients (mean age 73.8 ± 12.4 years; 54.8% male), 16.6% (n=67) died during hospitalization. Non-survivors were significantly older and had higher admission SUA, troponin, and CRP levels (all p<0.001). In multivariable analysis, advanced age (OR: 1.07; 95% CI: 1.03-1.08; p=0.007), troponin >14 ng/L (OR: 2.23; 95% CI: 1.21-4.01; p=0.012), CRP >5 mg/L (OR: 2.93; 95% CI: 1.59-5.67; p=0.001), and SUA >7 mg/dL (OR: 1.93; 95% CI: 1.04-3.53; p=0.041) were independently associated with in-hospital mortality. CRP showed the highest discriminatory performance (AUC: 0.77), while troponin (AUC: 0.67) and SUA (AUC: 0.66) demonstrated limited discriminatory ability. CONCLUSION: Admission CRP, troponin, and SUA levels were independently associated with in-hospital mortality in acute stroke patients. However, given their moderate discriminatory performance and the absence of standardized stroke severity scores, these biomarkers should be interpreted as supplementary risk indicators rather than standalone prognostic tools. Prospective multicenter studies incorporating stroke severity scales are warranted.
Regulatory T Cells Along the Pancreatitis-Pancreatic Cancer Continuum: Context-Dependent Immune Control and Therapeutic Opportunities.
Li H, Wang P, Chen H … +3 more , Wang C, Al-Danakh A, Jiang Z
Int J Gen Med · 2026 · PMID 42344105 · Full text
Regulatory T cells (Tregs) are essential for maintaining immune tolerance and limiting collateral tissue injury during inflammation. In pancreatic diseases, however, Treg function is highly context-dependent: protective...
Regulatory T cells (Tregs) are essential for maintaining immune tolerance and limiting collateral tissue injury during inflammation. In pancreatic diseases, however, Treg function is highly context-dependent: protective in acute inflammatory settings by restraining excessive immune activation, yet potentially pathogenic by fostering immunosuppression and immune escape in pancreatic ductal adenocarcinoma (PDAC). Acute pancreatitis (AP), chronic pancreatitis (CP), and PDAC share overlapping immune microenvironmental features, including cytokine-driven T-cell reprogramming, barrier dysfunction-associated microbial translocation, and stromal-immune crosstalk. Understanding Treg behaviour along the pancreatitis-PDAC continuum requires deciphering context-dependent immune microenvironmental mechanisms that shift from protective regulation to tumour-promoting immunosuppression. Recent evidence highlights that indiscriminate Treg depletion may paradoxically accelerate pancreatic tumorigenesis in specific settings, underscoring the need to resolve Treg heterogeneity, tissue residency, and stage-specific roles. In this review, we summarise current mechanistic insights into Treg-mediated regulation in AP and CP (including Th17/Treg balance and fibrosis-associated immune networks) and in PDAC (including Treg phenotypic diversity and interactions with myeloid cells and stroma). We further discuss emerging therapeutic strategies that modulate Tregs directly or indirectly, and propose a translational framework for aligning Treg-targeted interventions with disease stage and immune context to improve outcomes in pancreatic inflammation and cancer.
Predictive Value of Combined Serum NOX4, Gal-13, and Cyclophilin A for Prognosis in Severe Pneumonia.
Liu Q, Meng H, Sun H
Int J Gen Med · 2026 · PMID 42339175 · Full text
OBJECTIVE: To analyze the predictive value of the combined use of serum NADPH oxidase 4 (NOX4), galectin-13 (Gal-13), and cyclophilin A (CyPA) for poor prognosis in patients with severe pneumonia(SP). METHODS: This study...
OBJECTIVE: To analyze the predictive value of the combined use of serum NADPH oxidase 4 (NOX4), galectin-13 (Gal-13), and cyclophilin A (CyPA) for poor prognosis in patients with severe pneumonia(SP). METHODS: This study was a retrospective study.A total of 172 patients with SP admitted to our hospital from September 2023 to September 2025 were enrolled. They were assigned into the good prognosis group (n=98) and the poor prognosis group (n=74) according to the prognosis at 28 days. The levels of NOX4, Gal-13 and CyPA in the serum of patients were detected by ELISA. The point-biserial method was conducted to analyze correlations. Logistic method was conducted to discuss the influencing factors.Receiver operating characteristic (ROC) curve was used to discuss the predictive efficiency. In addition, decision curve analysis(DCA) was used to analyze their clinical application value. RESULTS: The CPIS score and the levels of serum CRP, PCT, NOX4, Gal-13 and CyPA in the poor prognosis group were higher than those in the good prognosis group (<0.05). The prognosis of SP patients 28 days after admission was positively correlated with the levels of serum NOX4 ( =0.517, <0.001), Gal-13 ( =0.539, <0.001), and CyPA ( =0.485, <0.001) at admission. Higher CPIS score, CRP, PCT, NOX4, Gal-13 and CyPA levels were risk factors for poor prognosis (<0.05). The area under the curve (AUC) of the joint prediction of serum NOX4, Gal-13 and CyPA levels for poor prognosis in SP patients was 0.939. Within the high-risk range of 0.07 to 0.94, the joint prediction of serum NOX4, Gal-13 and CyPA levels for the prognosis of SP patients had obvious positive clinical benefits. CONCLUSION: Detecting the levels of serum NOX4, Gal-13 and CyPA in patients at admission can assist clinicians in evaluating the prognosis of patients with SP.
Model-Dependent Cardiovascular Risk Stratification in Obese Populations: Multicenter Study in Türkiye.
Düzen Oflas N, Oral A, Solmaz I … +37 more , Topaloglu US, Demir I, Dundar A, Kirik A, Kama Başcı O, Sen H, Binnetoglu E, Okuroglu N, Aydin A, Kaya ZI, Yıldız H, Acet A, Tazegül G, Sozel H, Ozudogru O, Issever K, Yaylacı S, Korkmaz UB, Küçük C, Konur K, Ayaz T, Isiklar A, Arac E, Sumbul HE, Öztürk HA, Govez AB, Durmus YÜ, Onmez A, Ocak Serin S, Koca N, Yalcın N, Ertinmaz A, Güven AT, Kok M, Alp HH, Sahinturk Y, Uyar S
Int J Gen Med · 2026 · PMID 42339174 · Full text
BACKGROUND: Cardiovascular risk prediction models are essential for preventive cardiology; however, most were developed in populations with limited representation of individuals with severe obesity. Given the high preval...
BACKGROUND: Cardiovascular risk prediction models are essential for preventive cardiology; however, most were developed in populations with limited representation of individuals with severe obesity. Given the high prevalence of obesity in Türkiye and its strong association with cardiometabolic disorders, uncertainty exists regarding the applicability and agreement of contemporary cardiovascular risk estimation tools in this population. This study aimed to compare cardiovascular risk estimates derived from SCORE2, SCORE2-DM, and AHA PREVENT models across geographical regions in a large obese cohort from Türkiye, and to formally evaluate inter-model agreement and confounder-adjusted regional differences. METHODS: This multicenter retrospective analysis included 6,378 obese individuals recruited from seven geographical regions of Türkiye. Demographic characteristics, comorbidities, anthropometric measurements, and laboratory data were obtained from standardized electronic medical records. Ten-year cardiovascular risk was estimated, rather than prospectively predicted, using SCORE2, SCORE2-DM, and AHA PREVENT equations. Regional comparisons were performed using the Kruskal-Wallis test and chi-square analysis. Inter-model agreement was assessed using Spearman correlation, intraclass correlation coefficients (ICC), Bland-Altman analysis, and linear-weighted Cohen's kappa for guideline-based risk strata. Multivariable linear regression was used to evaluate regional differences after adjustment for age, sex, smoking, diabetes, hypertension, dyslipidemia, statin use, and body mass index. Statistical significance was set at p<0.05. RESULTS: Substantial regional heterogeneity was observed in smoking prevalence, cardiometabolic comorbidities, and medication use. Cardiovascular risk estimates differed according to the selected prediction model: SCORE2 identified the highest median risk in Mediterranean and Southeastern Anatolia, SCORE2-DM demonstrated relatively homogeneous risk estimates across regions, and PREVENT showed greater regional discrimination, identifying the highest risk in the Aegean region and the lowest risk in Eastern and Central Anatolia. SCORE2 and PREVENT showed strong rank-order agreement (Spearman =0.95) but only modest categorical agreement (weighted κ=0.31). SCORE2-DM systematically estimated 10-year risk approximately 6 percentage points higher than PREVENT (mean difference 6.37%, 95% LoA 5.70 to 7.04). Regional differences in risk estimates remained statistically significant after multivariable adjustment for all three models (all p≤0.009). CONCLUSION: Cardiovascular risk estimation in obese individuals is highly sensitive to the choice of prediction model and regional population characteristics. Although the three contemporary models rank patients similarly, their absolute risk estimates and categorical risk classifications can diverge substantially, particularly in obese patients with diabetes. Because this analysis is based on model-derived estimates rather than observed cardiovascular outcomes, our findings should be interpreted as descriptive risk estimation rather than validated risk prediction. These findings highlight the importance of cautious interpretation of risk scores and emphasize the need for outcome-based, population-specific validation of cardiovascular risk prediction tools in high-risk obese populations.
Undiagnosed and Uncontrolled Hypertension in the Aseer Region, Saudi Arabia: A Ramadan Screening Study with Long-Term Trends (1990-2019) and Projections to 2027.
Al-Qahtani FS, Battar SS, Musharraf MH … +5 more , AlAmri AM, Alsamghan A, Alshaikh AA, Alahmari MD, Ghazy RM
Int J Gen Med · 2026 · PMID 42333388 · Full text
BACKGROUND: Community-based screening initiatives can facilitate early detection and link individuals to care. This study aimed to assess the prevalence of diagnosed and undiagnosed hypertension among adults in the Aseer...
BACKGROUND: Community-based screening initiatives can facilitate early detection and link individuals to care. This study aimed to assess the prevalence of diagnosed and undiagnosed hypertension among adults in the Aseer region during Ramadan and contextualize these findings within national hypertension trends using World Health Organization (WHO) data from 1990 to 2019, with projections to 2027. METHODS: A cross-sectional study was conducted from March 11-18, 2025, including 657 adults. Participants were classified as non-hypertensive, previously diagnosed, or having undiagnosed hypertension. Multinomial logistic regression was used to identify factors associated with hypertension status. Secondary analysis of WHO data was performed to examine national trends in hypertension prevalence and projection using autoregressive integrated moving average (ARIMA) and Poisson regression models. RESULTS: Primary data revealed that 56.3% had undiagnosed hypertension (stage 1: 43.8% and stage 2: 56.2%) and 16.6% had a prior diagnosis (stage 1: 27.5% and stage 2: 62.4%). Older age (adjusted odds ratio (aOR): 17.17, 95% CI 4.80-61.42 for ages 55-64), male sex (aOR: 2.24, 95% CI 1.16-4.33), higher body mass index (aOR: 1.10, 95% CI 1.05-1.15), diabetes (aOR: 2.23, 95% CI 1.14-4.37), and self-reported dyslipidemia (aOR: 3.52, 95% CI 1.72-7.24) were independent predictors of diagnosed hypertension. Male sex and higher BMI were also significant predictors of undiagnosed hypertension. Between 1990-2019, secondary data revealed that females showed a significant decline in the prevalence of hypertension from 34.1% (95% CI: 21.5-49.2) to 30.2% (95% CI: 21.4-40.1) (APC: -0.58%), while prevalence among males increased from 34.4% (95% CI: 21.5-49.1) to 36.3% (95% CI: 26.6-46.7) (APC: 0.18%). Overall prevalence decreased slightly from 34.4% (95% CI: 24.9-45.1) to 34.0% (95% CI: 27.1-41.5) (APC: -0.4%). Forecasts for 2027 predicted a continued decline among females to 27.47% (95% prediction interval (PI): 26.42-28.51) (APC: -2.73%) and a modest increase among males to 36.82% (95%PI: 36.55-37.09) (APC: 1.4%), with the total prevalence projected to decrease slightly to 33.39% (95%PI: 32.64-34.14) (APC: -1.01%). CONCLUSION: Ramadan-based screening revealed a high burden of undiagnosed and uncontrolled hypertension. Along with forecasts of rising male but falling female prevalence, this underscores the urgent need for targeted community-based screening, education, and management to improve hypertension awareness and control.
Innovative Insights into Interleukin-Mediated Macrophage Polarization: Metabolic Reprogramming and Inflammatory Pathway Crosstalk in Chronic Kidney Disease and Therapeutic Implications-A Narrative Review.
Jiang Z, Zhang X, Jin L … +5 more , Han M, Zhang Y, Jiang Y, Zhang J, Jin L
Int J Gen Med · 2026 · PMID 42325941 · Full text
OBJECTIVE: To clarify the molecular mechanisms of interleukin-macrophage polarization axis in reshaping renal inflammatory microenvironment and driving chronic kidney disease (CKD) progression, and explore targeted thera...
OBJECTIVE: To clarify the molecular mechanisms of interleukin-macrophage polarization axis in reshaping renal inflammatory microenvironment and driving chronic kidney disease (CKD) progression, and explore targeted therapeutic potential. METHODS: We systematically searched the PubMed and Embase databases for published studies from January 2015 to March 2026. The search terms used were "chronic kidney disease" or "CKD", "interleukin" or "IL" or "leukocyte protein network", "macrophages" and "inflammation". A total of 186 peer-reviewed studies based on human and animal models were included, with all non-eligible articles excluded in the screening process. RESULTS: Pro-inflammatory interleukins (IL-1β/IL-6/IL-17) orchestrate M1 polarization via multi-pathway crosstalk: IL-1β activates NLRP3 inflammasome to promote IL-18 release, IL-6 binds gp130 to trigger STAT3, and IL-17 activates NF-κB/MAPK, all upregulating glycolytic enzymes (HK2/PFKFB3) and M1 markers (iNOS/CD86). Activated M1 macrophages secrete TNF-α/IL-1β/IL-6, forming an autocrine loop to amplify renal parenchymal injury and monocyte recruitment. Anti-inflammatory interleukins (IL-10/IL-22) induce protective M2 polarization: IL-4 activates STAT6 to upregulate CD206/Arg1, IL-10 inhibits NF-κB, and IL-22 modulates AMPK-mediated mitophagy. However, CKD-induced M2 pathological deviation (elevated TGF-β/CTGF, reduced IL-10) converts reparative functions to profibrotic effects, accelerating glomerulosclerosis. This polarization imbalance forms a vicious cycle with interleukin dysregulation. Targeted interventions show efficacy: tocilizumab (anti-IL-6R) reduces M1 infiltration and urinary albumin; paeoniflorin upregulates IL-10 via KLF4 to induce M2; SGLT2 inhibitors enhance IL-22/AMPK signaling; astragaloside IV promotes IL-4/PPARγ to stabilize M2 polarization, all alleviating inflammation and fibrosis. CONCLUSION: The interleukin-macrophage polarization axis, regulated by inflammatory pathways and metabolic reprogramming, is a core CKD therapeutic target, supporting multi-target precision interventions.
Integrating Network Pharmacology and Clinical Observation to Elucidate the Therapeutic Mechanisms of Yangzheng Xiaoji Decoction in Primary Liver Cancer.
Yang S, Liu R, Wen S … +3 more , Wang Y, Tai N, Tian J
Int J Gen Med · 2026 · PMID 42325940 · Full text
BACKGROUND: Primary liver cancer (PLC) is a leading cause of global cancer mortality. Yangzheng Xiaoji Decoction (YZXJD), a traditional Chinese medicine based on "Fuzheng Xiaoji" principles, is used as adjunctive PLC the...
BACKGROUND: Primary liver cancer (PLC) is a leading cause of global cancer mortality. Yangzheng Xiaoji Decoction (YZXJD), a traditional Chinese medicine based on "Fuzheng Xiaoji" principles, is used as adjunctive PLC therapy, yet its underlying molecular mechanisms require further characterization. METHODS: Active compounds from 13 herbs were retrieved via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database (OB ≥ 30%, DL ≥ 0.18). After identifying drug-disease target intersections, a compound-target-disease network was constructed using Cytoscape. PPI, GO, and KEGG analyses were performed. Concurrently, 40 patients with PLC were assigned, in a non-randomized prospective controlled design, to conventional therapy (control, n=20) or conventional therapy plus YZXJD (observation, n=20) for 4 weeks. Biochemical markers (AFP, AST, ALT, ALB, PT) and TCM syndrome scores were evaluated. RESULTS: Network pharmacology identified 195 active compounds and 135 potential therapeutic targets. PPI screening revealed 25 core targets, with GRM5, TRPA1, ADRA1D, GRIA2, and NPY2R showing the highest connectivity. GO analysis yielded 215 enriched terms, while KEGG analysis highlighted 14 pathways, notably neuroactive ligand-receptor interaction and cGMP-PKG signaling. Clinically, both groups showed within-group reductions in AST, ALT, and AFP, but under a Bonferroni-adjusted threshold (P < 0.01) the between-group advantage for the observation group was most clearly evident for prothrombin time (PT), which improved in the observation group while it worsened in the control group. TCM syndrome scores decreased significantly in the observation group (P < 0.001) but worsened in the control group (P = 0.004). The total effective rate was 80.0% in the observation group versus 65.0% in controls (P = 0.048). CONCLUSION: Network pharmacology suggests that YZXJD may act against PLC through multi-component, multi-pathway mechanisms. In this preliminary, non-randomized observation, the addition of YZXJD was associated with improvements in hepatic function markers, serum AFP, and symptom burden. These findings are hypothesis-generating; the computational predictions and clinical signals require confirmation in adequately powered, randomized, and experimentally validated studies before YZXJD can be recommended for routine integration into PLC management.
The Gut-Disc Axis: Mendelian Randomization Study Reveals Causal Effects of Gut Microbiota on Intervertebral Disc Degeneration Not Mediated by Systemic Inflammation.
Yan Z, Jiang Q, Lu Z … +4 more , Cao S, Bai J, Ni Z, Ding Y
Int J Gen Med · 2026 · PMID 42325939 · Full text
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain. Observational studies suggest a link with gut microbiota (GM), possibly mediated by systemic inflammation, but causality remains uncl...
BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain. Observational studies suggest a link with gut microbiota (GM), possibly mediated by systemic inflammation, but causality remains unclear. OBJECTIVE: To assess the suggestive associations of GM and inflammatory cytokines (ICs) on IVDD using Mendelian randomization (MR), and evaluate potential mediation by ICs. METHODS: We performed a two-sample MR analysis. Genetic instruments for GM came from MiBioGen (n=18,340), for 41 ICs from a meta-analysis (n=8337), and for IVDD from FinnGen (29,508 cases/227,388 controls). Inverse-variance weighted (IVW) was the primary method. Mediation was assessed via two-step MR, with sensitivity analyses (MR-Egger, MR-PRESSO). RESULTS: At the nominal significance level (), 11 microbial taxa showed suggestive causal associations with IVDD risk, of which only Eubacterium coprostanoligenes group approached the Bonferroni-corrected threshold ( ). Seven inflammatory cytokines showed suggestive associations with IVDD; however, none remained statistically statistically significant after Bonferroni correction. Mediation analysis revealed no statistically statistically significant indirect effect of cytokines linking gut microbiota to IVDD. CONCLUSION: This study provides genetic evidence supporting a potential gut-disc axis. The lack of evidence for cytokine mediation does not exclude alternative pathways but indicates insufficient support for systemic cytokine-mediated mechanisms among those examined; future mechanistic studies should explore microbial metabolites and local immune activity.
Serial C-Reactive Protein Measurements for Prognostication and Antimicrobial Decision-Making in ICU Sepsis Patients: A Retrospective Cohort Study.
Al-Dorzi HM, Aleid AM, Alqahtani AA … +2 more , Alwarafi AA, Alwahbi SF
Int J Gen Med · 2026 · PMID 42325938 · Full text
BACKGROUND: C-reactive protein (CRP) is a widely used biomarker for sepsis management; however, its prognostic value remains uncertain. This study evaluated whether serial CRP measurements are associated with mortality i...
BACKGROUND: C-reactive protein (CRP) is a widely used biomarker for sepsis management; however, its prognostic value remains uncertain. This study evaluated whether serial CRP measurements are associated with mortality in intensive care unit (ICU) patients with sepsis. METHODS: This retrospective cohort study included adult patients admitted to a tertiary-care ICU between 2020 and 2023, who had at least three serial CRP measurements around days 1, 3, and 7 to guide sepsis management as diagnosed by the treating team. We examined the relationship between CRP levels and 90-day mortality. RESULTS: The study included 171 patients (median age: 67 years; 55% male). Compared to patients with lower CRP levels, those with day-1 CRP ≥75 mg/L (n=87, 50.9%) had similar clinical characteristics, except for a higher prevalence of malignancy. Antibiotic use and clinical outcomes were similar between the groups. Meropenem duration tended to be shorter in patients whose CRP levels decreased from days 1 to 7 than in those whose CRP levels increased (median 7 days vs. 10 days; p=0.06). 42 patients (24.6%) died within 90 days. Compared to survivors, non-survivors had slightly higher CRP levels on day 1 (91 mg/L vs. 70 mg/L, p=0.08) and similar changes in CRP over time. Receiver operating characteristic curve analysis demonstrated that both CRP levels and their temporal changes had poor prediction for 90-day mortality (area under the curve for day-1 CRP, 0.590), with day-1 procalcitonin performing slightly better (area under the curve, 0.658). In the multivariable logistic regression analysis, day-1 CRP was not associated with 90-day mortality. CONCLUSION: Serial CRP measurements did not reliably predict mortality in ICU patients with sepsis but may have influenced the antibiotic duration. Routine CRP monitoring in ICU patients with sepsis may have a limited prognostic value.
Value of Color Doppler Echocardiography for Predicting Heart Failure After Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction.
Ren L, Hu Z, Huang Z … +1 more , Xu L
Int J Gen Med · 2026 · PMID 42311756 · Full text
PURPOSE: To evaluate the role of color Doppler echocardiography in assessing ventricular remodeling and post-percutaneous coronary intervention (PCI) heart failure (HF) in patients with acute myocardial infarction (AMI)....
PURPOSE: To evaluate the role of color Doppler echocardiography in assessing ventricular remodeling and post-percutaneous coronary intervention (PCI) heart failure (HF) in patients with acute myocardial infarction (AMI). METHODS: 81 AMI patients admitted to our hospital were selected for retrospective analysis, including 49 patients who underwent PCI (research group, RG) and 32 patients who did not undergo PCI (control group, CG). Both groups of patients were followed up for 6 months. Left ventricular (LV) end-diastolic volume (LVEDV), LV end-diastolic dimension (LVEDD), LV end-diastolic dimension (LVESD) and LV ejection fraction (LVEF) were measured using a Philips iE33 ultrasound system. To assess ventricular remodeling dynamically, LVEDVI was additionally measured at 7 days (T2), 1 month (T3), and 6 months (T4) after treatment, and ΔLVEDVI was calculated as the difference between LVEDVI at each follow‑up time point and the baseline value at T1. Receiver operating characteristic (ROC) curve was used to analyze the sensitivity of LVEDD, LVESD and LVEF to predict HF. Multivariate logistic regression analysis was used to analyze the factors associated with HF progression. RESULTS: Elevated ΔLVEDVI levels was observed in both cohorts at T2-T4 compared with the value at T1, with significantly lower ΔLVEDVI in the RG than in the CG at each time point (<0.05). Among the 11 patients who developed post-PCI HF in the research group, significant increases in LVEDD and LVESD and a significant decrease in LVEF (<0.05). Based on ROC analysis, color Doppler echocardiography demonstrated excellent diagnostic performance for post-PCI HF (<0.05). The number of coronary artery lesions, Gensini score, hypertension, and color Doppler echocardiography results at T1 were independent risk factors for post-PCI HF (<0.05). CONCLUSION: Color Doppler echocardiography demonstrated excellent performance in evaluating ventricular remodeling and post-PCI HF in AMI patients and may provide a reliable reference for future clinical management of AMI.
Circular RNA Hsa_circ_0062403 Acts as a Potential Prognostic Biomarker for Early Recurrence of Hepatocellular Carcinoma.
Yu X, Shan Y, Lu C … +1 more , Mao S
Int J Gen Med · 2026 · PMID 42311755 · Full text
PURPOSE: Circular RNAs (circRNAs) have been shown to have critical regulatory roles in hepatocellular carcinoma (HCC). This study aims to investigate the predictive value of circLZTR1 for early recurrence of HCC. PATIENT...
PURPOSE: Circular RNAs (circRNAs) have been shown to have critical regulatory roles in hepatocellular carcinoma (HCC). This study aims to investigate the predictive value of circLZTR1 for early recurrence of HCC. PATIENTS AND METHODS: In this study, circLZTR1 (a circRNA derived from the LZTR1, hsa_circ_0062403) was identified and validated in the HCC cohort. Univariate analyses and multivariate Cox regression were conducted to analyze the functional role of hsa_circ_0062403 in the postoperative early recurrence of HCC patients. Receiver operating characteristic curve (ROC) analysis was performed to assess the predictive performance of hsa_circ_0062403 for early recurrence. RESULTS: 91 patients with HCC after surgery were included. circLZTR1 was downregulated in early recurrence HCC patients and predicted poor recurrence-free survival (P=0.029). In addition, a significant downregulation of circLZTR1 was observed in HCC from patients with MVI or PVTT. Multivariate Cox regression analysis indicated that lower circLZTR1 (>0.25 vs <0.1; HR = 0.142, 95% CI: 0.042-0.482, P = 0.002), higher AFP (>400 vs <20; HR = 7.880, 95% CI: 2.499-24.844, P < 0.001), higher INR (HR = 4.203, 95% CI: 1.133-15.588, P = 0.032), multiple tumors (HR = 3.795, 95% CI: 1.541-9.346, P = 0.004), PVTT positive (HR = 3.438, 95% CI: 1.050-11.258, P = 0.041), and larger tumor diameter (HR = 1.306, 95% CI: 1.101-1.550, P = 0.002) served as independent risk factor for early recurrence of HCC. ROC analysis indicated that the Cox model demonstrated higher sensitivity and specificity than the clinical model and single circLZTR1 in prediction for early recurrence of HCC patients (AUC = 0.767, 95% CI: 0.666-0.868, P < 0.001). CONCLUSION: The downregulation of circLZTR1 is closely associated with the acquisition of invasive phenotypes, vascular invasion, and subsequent early recurrence of HCC patients, suggesting that circLZTR1 may serve as a novel prognostic biomarker for predicting early recurrence in patients with HCC.
A Multi-Center Study: Developing a Nomogram for Predicting Genetic Results of Trio-Based Whole-Exome Sequencing (Trio-WES) in Diagnosing Children with Syndromic Neurodevelopmental Disorders (s-NDDs).
Wu R, Qiu R, Tang D … +4 more , Meng Z, Li X, Li D, Tang W
Int J Gen Med · 2026 · PMID 42311754 · Full text
OBJECTIVE: The diagnostic efficacy of empirical trio-based whole-exome sequencing (trio-WES) for unexplained syndromic neurodevelopmental disorders (NDDs) remains unsatisfactory. This study aimed to explore the diagnosti...
OBJECTIVE: The diagnostic efficacy of empirical trio-based whole-exome sequencing (trio-WES) for unexplained syndromic neurodevelopmental disorders (NDDs) remains unsatisfactory. This study aimed to explore the diagnostic value of phenotypic indicators and establish a nomogram for predicting the genetic results of trio-WES for diagnosing patients with unexplained s-NDDs. METHODS: We retrospectively collected phenotypic and genotypic data from 265 children with s-NDDs who received trio-WES at Sun Yat-sen Memorial Hospital (training cohort), 38 and 97s-NDDs patients with trio-WES test at Shenshan Medical Center (validation cohort-1) and Weierkang Children's Rehabilitation Center (validation cohort-2), respectively. Logistic analysis was employed to identify the independent predictors of a positive trio-WES diagnosis in the training cohort for model establishment. The predictive performance and robustness of the model were assessed using receiver operating characteristic (ROC) and confusion matrix analyses, respectively. RESULTS: The analysis revealed that the severity of neurodevelopmental delays, head circumference abnormality, and complexity of neurodevelopmental comorbidities were independent predictive indicators for distinguishing s-NDDs patients with positive trio-WES results. The nomogram combining the three predictors showed good predictive performance with an area under the ROC (AUC) in the training cohort of 0.827 (95% CI: 0.775-0.879), yielding a confusion matrix with sensitivity, specificity, accuracy, precision, and F1 score of 78.23%, 78.01%, 78.11%, 75.78%, and 0.77, respectively. The model also had an excellent prediction in the external validation cohorts (AUC: 0.953; 95% CI: 0.881-0.998, sensitivity: 88.89%; specificity: 80.00%; accuracy: 84.21%; precision: 80.00%; and F1 score: 0.84 in validation cohort-1 and AUC: 0.910; 95% CI: 0.843-0.978, sensitivity: 83.33%; specificity: 85.45%; accuracy: 84.54%; precision: 81.40%; and F1 score: 0.82 in validation cohort-2). CONCLUSION: The model can serve as a useful tool for assisting decision-making in applying trio-WES in the diagnostic strategy for s-NDDs, helping to implement personalized pre-diagnosis assessments for affected families.
Cigarette and Electronic Cigarette Exposure in Osteoarthritis: Immune Dysregulation and Inflammatory Signaling Pathways.
Liu J, Tang J, Ma Z … +2 more , Wang Z, Zhang H
Int J Gen Med · 2026 · PMID 42306583 · Full text
Osteoarthritis (OA) was once seen mainly as a degenerative joint disease, but more studies now show that inflammation also has an important role in its development and progression. Smoking may be one factor in this proce...
Osteoarthritis (OA) was once seen mainly as a degenerative joint disease, but more studies now show that inflammation also has an important role in its development and progression. Smoking may be one factor in this process. Findings from population studies are still not fully consistent, but cigarette exposure is known to affect immune function and inflammatory signaling. This suggests that its role in OA may be more complex than a simple risk factor. At the same time, the fast growth of electronic cigarettes (EC) use has raised new concerns, because its effects on joint tissues are still not clear. In this Perspective, we discuss how cigarette and EC exposure may affect OA through several related pathways, including synovial macrophage activation, damage-associated molecular pattern (DAMP)-mediated signaling, NF-κB activation, inflammasome activation, Th17/Treg imbalance, and changes in microRNA expression. These changes may disturb the synovial-cartilage microenvironment, increase cytokine and chemokine production, and promote joint tissue damage. We also discuss current problems in this field, such as inconsistent epidemiological results, limited OA-specific mechanistic studies, and the lack of reliable models for EC exposure.
Composite Ultrasound Score Integrating VExUS Grading and Right Ventricular Function for Predicting 90-Day Heart Failure Rehospitalization: A Single-Center Retrospective Cohort Study.
Tang H, Teng L, Xing X … +4 more , Niu Q, Guo Y, Zhu X, Liu Z
Int J Gen Med · 2026 · PMID 42306582 · Full text
PURPOSE: Systemic venous congestion and right ventricular (RV) dysfunction are important determinants of adverse outcomes in heart failure (HF). This study evaluated the prognostic value of a Composite Ultrasound Score i...
PURPOSE: Systemic venous congestion and right ventricular (RV) dysfunction are important determinants of adverse outcomes in heart failure (HF). This study evaluated the prognostic value of a Composite Ultrasound Score integrating Venous Excess Ultrasound (VExUS) grading and multiparametric RV systolic function for predicting 90-day HF rehospitalization. PATIENTS AND METHODS: This single-center retrospective cohort study included 712 patients hospitalized for HF who underwent pre-discharge echocardiographic assessment. The Composite Ultrasound Score ranged from 0 to 3 and combined VExUS-derived venous congestion with RV systolic dysfunction defined by TAPSE, RV S', and RV fractional area change. The primary endpoint was 90-day HF rehospitalization. Predictive performance was assessed using Cox regression, Harrell's C-index, time-dependent receiver operating characteristic analysis, and decision curve analysis. RESULTS: During follow-up, 154 patients (21.6%) were rehospitalized. The Composite Ultrasound Score showed higher discrimination (C-index: 0.79; 95% CI: 0.75-0.83) than VExUS grading alone (0.74; P = 0.012), NT-proBNP (0.71; P < 0.001), or individual RV parameters. A score ≥2 identified a high-risk group with a 90-day event rate of 50.0% versus 8.3% in the low-risk group (log-rank P < 0.001). A high score remained independently associated with rehospitalization (adjusted HR: 2.85; 95% CI: 1.95-4.16; P < 0.001). The association was stronger in patients with chronic kidney disease (P for interaction = 0.038). Decision curve analysis suggested greater net benefit than single-parameter strategies. CONCLUSION: The Composite Ultrasound Score was independently associated with 90-day HF rehospitalization and showed moderate incremental prognostic value in this single-center retrospective cohort. It may serve as a promising adjunctive tool for pre-discharge risk stratification, particularly in patients with cardiorenal vulnerability. Prospective multicenter validation is required before routine clinical implementation.
miR-1287-5p as a Biomarker for Predicting Lymph Node Metastasis in Gastric Cancer Patients.
Zhang J, Zhang M, Zhao W … +2 more , Wu H, Wang R
Int J Gen Med · 2026 · PMID 42306581 · Full text
BACKGROUND: The purpose of this study was to predict lymph node metastasis (LNM) in gastric cancer (GC) patients by constructing a nomogram. METHODS: A total of 416 GC patients from the TCGA database and the Second Hospi...
BACKGROUND: The purpose of this study was to predict lymph node metastasis (LNM) in gastric cancer (GC) patients by constructing a nomogram. METHODS: A total of 416 GC patients from the TCGA database and the Second Hospital of Hebei Medical University were included. The TCGA cohort was used to develop the prediction model. Logistic regression was used to determine risk factors associated with LNM in GC patients. A nomogram model was then developed. Model performance was evaluated using the area under the curve (AUC) and calibration curves. RESULTS: In the multivariate analysis, the variables independently associated with LNM in GC patients were race (OR=1.820, 95% CI 1.060-3.125), histologic grade (OR=0.587, 95% CI 0.354-0.974), pathologic stage T3 or higher (OR=2.081, 95% CI 1.188-3.647) and miR-1287-5p (OR=0.748, 95% CI 0.565-0.992). A nomogram comprising the above four independent factors was constructed to calculate the possibility of LNM. The C-index values were 0.847 (95% CI 0.777-0.917) and 0.755 (95% CI 0.565-0.944) in the training and supportive cohorts, respectively. CONCLUSION: We identified miR-1287-5p as a novel predictor of LNM in GC patients. We established a nomogram model for predicting LNM in GC patients, and evaluated its performance in a supportive cohort.
Research Progress of SGLT2 Inhibitors in the Treatment of Acute Heart Failure: A Narrative Review.
Wang X, Ning Y, Wang X … +3 more , Li G, Wang X, Wu D
Int J Gen Med · 2026 · PMID 42306580 · Full text
Acute heart failure (AHF) is the main cause of hospitalization in patients with heart failure (HF). Although traditional therapies play an important role in symptom relief, their efficacy in reducing mortality, rehospita...
Acute heart failure (AHF) is the main cause of hospitalization in patients with heart failure (HF). Although traditional therapies play an important role in symptom relief, their efficacy in reducing mortality, rehospitalization rates, and improving long-term prognosis remains unsatisfactory. In recent years, sodium‑glucose cotransporter 2 (SGLT2) inhibitors, originally developed as glucose‑lowering agents, have demonstrated significant benefits in chronic heart failure, and their potential utility in AHF is attracting increasing attention. Current evidence indicates that early initiation of SGLT2 inhibitors in patients with AHF is generally safe, improving diuretic efficiency, relieving congestion, and reducing the risk of heart failure events. However, findings on short‑term readmission rates remain inconsistent across studies. Furthermore, unresolved issues persist regarding the optimal timing of initiation and safety in specific patient populations. This narrative review summarizes the available evidence up to 31 March 2026, with emphasis on key clinical trials, including DAPA ACT HF-TIMI 68, and selected real-world studies. We discuss the potential benefits, safety considerations, unresolved controversies, and evidence gaps regarding the use of SGLT2 inhibitors in AHF, aiming to provide a clinically oriented reference for future research and practice.
Effects of High-Intensity Interval Training on Cardiopulmonary Function in Patients with Acute Myocardial Infarction with and without Cardiac Arrest: A Retrospective Study.
Zeng Y, Zhang Z, Wu J … +4 more , Ge P, Xu J, Liu H, Geng J
Int J Gen Med · 2026 · PMID 42299233 · Full text
OBJECTIVE: This study aims to explore the efficacy and safety of high-intensity interval training (HIIT) in patients with acute myocardial infarction (AMI) with or without cardiac arrest (CA). METHODS: A retrospective an...
OBJECTIVE: This study aims to explore the efficacy and safety of high-intensity interval training (HIIT) in patients with acute myocardial infarction (AMI) with or without cardiac arrest (CA). METHODS: A retrospective analysis of 100 patients with AMI who underwent primary percutaneous coronary intervention was conducted. Fifty patients experienced CA, whereas the other fifty did not. A HIIT program was performed three times per week for a 12-week duration. The target heart rate (THR) method was used to guide the intensity of exercise. The cardiopulmonary function indices include maximum oxygen uptake (VO max), anaerobic threshold (AT), ventilatory efficiency (E/CO slope), oxygen uptake efficiency slope (OUES), metabolic equivalents (METs), oxygen pulse (VO/HR), and heart rate recovery at 1 minute (HRR). RESULTS: After HIIT, VOmax in the CA group increased from 21.96±4.40 to 23.85±3.28 mL/kg/min (95% CI: 1.31 to 2.47; P <0.001). AT increased from 15.01±3.09 to 15.97±2.09 mL/kg/min (95% CI: 0.41 to 1.51; P =0.001), while the VE/VCO slope decreased from 29.26±3.14 to 27.56±4.42 L/l (95% CI: -3.01 to -0.39; P =0.047). OUES increased from 1762.49±653.77 to 1960.08±527.43 (95% CI: 55.00 to 340.18; P =0.0078). METs increased from 6.27±1.25 to 6.81±0.93 (95% CI: 0.37 to 0.71; P <0.001). Additionally, oxygen pulse (O/HR) increased from 12.32±2.08 to 13.74±0.90 mL (95% CI: 0.87 to 1.97; P <0.001), and HRR improved from 16.65±7.75 to 20.1±6.64 (95% CI: 0.87 to 6.03; P =0.010); similar improvements were also observed in the non-CA group. The adverse events during rehabilitation were comparable between the two groups. CONCLUSION: Overall, HIIT-based rehabilitation was associated with significant improvements in cardiopulmonary function, with comparable outcomes in AMI patients with and without CA.
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