ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

Objective: To evaluate the risk of donation-related adverse reactions, donation behavior, and contributions to the blood supply among donors aged 56-65 years following extension of the upper age limit for voluntary blood donation, and to provide real-world evidence for optimizing blood donation age policies in China. Methods: A multicenter retrospective cohort was established using blood donation databases from Hainan, Shenzhen, and Jiangxi. A total of 1 180 767 donors contributing 2 020 407 whole-blood and apheresis donations were included. Donations were classified by donor age at each donation into the 18-55-year and 56-65-year groups. Generalized estimating equation (GEE) models were used to compare the risks of overall, local, and systemic donation-related adverse reactions between the two age groups. Restricted cubic spline analysis was used to assess the continuous association between donor age and the risk of overall adverse reactions. Poisson GEE models were used to compare annual donation frequency, and donation participation and contributions to the blood supply among donors aged 56-65 years were evaluated. The study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (No.2025012) and registered with the Chinese Clinical Trial Registry (ChiCTR2500114960). Results: A total of 1 960 711 donations were included in the 18-55-year group and 59 696 in the 56-65-year group. The overall donation-related adverse reaction rates were 3.890‰and 0.704‰, respectively. Multivariable GEE analysis showed that, compared with donors aged 18-55 years, those aged 56-65 years had lower risks of overall adverse reactions (adjusted OR=0.294, 95%CI: 0.217-0.398, P<0.001) and systemic adverse reactions (adjusted OR=0.163, 95%CI: 0.101-0.263, P<0.001), whereas no statistically significant difference was observed in the risk of local adverse reactions (adjusted OR=1.337, 95%CI: 0.487-3.670, P=0.573). Donor age was nonlinearly associated with the risk of overall adverse reactions (P overall<0.001, P nonlinear<0.001), with the risk generally decreasing with increasing age between 18 and 65 years. The mean annual donation frequency was higher among donors aged 56-65 years than among those aged 18-55 years (1.63 vs 1.24 donations per year; adjusted IRR=1.34, 95%CI: 1.30-1.39, P<0.001). During the study period, donors aged 56-65 years contributed 2.95% of all donations; their whole-blood donations and whole-blood collection volume accounted for 2.36% and 2.37% of the corresponding totals, respectively. Conclusion: Under current health screening and standardized donor management, donors aged 56-65 years did not show an increased risk of short-term donation-related adverse reactions and demonstrated a higher annual donation frequency, together with a measurable contribution to the blood supply. These findings support appropriately extending the upper age limit for voluntary blood donation under strict health screening to broaden the donor pool and supplement the blood supply.

Objective: Some regions in China have lowered the minimum interval for whole blood donation to 3 months through local regulations: Hainan, effective from March 1, 2012, allows men to donate at intervals of≥3 months and women at intervals of≥4 months; Shenzhen, effective from November 1, 1995, allows whole blood donation at intervals of≥3 months. The aim of this study was to evaluate the impact of shortening the whole blood donation interval on blood donation adverse reactions and donation behavior, thereby providing scientific evidence for policy evaluation and revision of relevant regulations. Methods: This was a multicenter, retrospective cohort study based on blood donation registry data from Shenzhen and Hainan. Data were obtained from the blood information management systems of Hainan Province (1991-2025) and Shenzhen City (2018-2024). Eligible participants were donors aged 18-65 years who had donated whole blood at least twice and met health eligibility criteria. The exposure was defined as a shorter donation interval (whole-blood interval≥3 months and<6 months) and was treated as a time-varying variable. The primary outcome was blood donation adverse reactions. Negative binomial regression with person-years as an offset was used to estimate incidence rate ratios for adverse reactions. Marginal standardization was used to estimate the adjusted incidence rate difference, and donor-level bootstrap resampling was used to estimate the 95% confidence interval of the adjusted incidence rate difference. Non-inferiority was assessed by comparing the upper limit of the 95% confidence interval with the prespecified non-inferiority margin of Δ=0.00 070 per person-year. In addition, Andersen-Gill models were used to analyze adverse reaction-free probability for recurrent events. Secondary outcomes were donation behavior, including annual repeat donation rate, annual donation frequency, mean donation interval, and annual whole-blood donation volume. These were analyzed using logistic regression, negative binomial regression, and linear regression models, respectively, with adjustment for age, sex, region, and donation site. This study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (Approval No.2025011) and registered in the Chinese Clinical Trial Registry (ChiCTR2500114968). Results: A total of 375 075 repeat whole-blood donors were included, contributing 1 292 748 whole-blood donations. Among them, 119 993 had ever donated at a shorter interval and 255 082 had never done so. Over 1 281 842 person-years of follow-up in the dynamic cohort, 2 100 blood donation adverse reactions were recorded. The incidence rates of adverse reactions were 1.76 and 1.58 per 1 000 person-years in the ever-short interval and never-short interval groups, respectively. After adjustment for age, sex, province, and donation site, the ever-short interval group had a slightly higher adverse reaction rate than the never-short interval group (IRR=1.28, 95%CI: 1.15-1.41, P<0.001). Marginal standardization showed that the adjusted incidence rates were 1.73 and 2.21 per 1 000 person-years in the never-short interval and ever-short interval groups, respectively. The adjusted incidence rate difference was 0.000 48 per person-year, with a bootstrap 95%CI of 0.000 26-0.000 69 per person-year; the upper limit of the 95%CI was below the prespecified non-inferiority margin. Andersen-Gill recurrent-event analysis showed that the ever-short interval group had a higher probability of remaining adverse reaction-free. Analysis of donation behavior showed that among donors followed for at least 365 days, the ever-short interval group had a higher annual repeat donation rate than the never-short interval group (74.2% vs 18.3%; adjusted OR=12.5, 95%CI: 12.3-12.7, P<0.001). They also had a higher annual whole-blood donation rate (adjusted RR=1.98, 95%CI: 1.97-1.98, P<0.001), a shorter mean whole-blood donation interval (β=-239 days, 95%CI: -242 to -237 days, P<0.001), and a higher annual whole-blood donation volume (adjusted RR=2.14, 95%CI: 2.13-2.15, P<0.001). Conclusion: Based on real-world data from repeat whole-blood donors in Shenzhen and Hainan, lowering the minimum whole blood donation interval to 3 months did not show an absolute increase in blood donation adverse reactions exceeding the prespecified margin within the scope of this outcome. Shorter whole-blood donation interval behavior was also associated with greater repeat-donation activity, higher annual donation frequency, and higher annual whole-blood donation volume. Given the observational nature of this study and the lack of long-term donor health indicators such as iron status and longitudinal hemoglobin changes, the long-term safety of setting the minimum whole blood donation interval at 3 months requires further evaluation.

AIM:To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)in hypoxia-induced autophagy and apopto-sis in endothelial cells.METHODS:Human umbili-cal vein endothelial cells(HUVECs)were exposed to hypoxia(1％O2)for varying durations(0,6,12,24 h)to evaluate autophagy and apoptosis levels.LOX-1 was further intervened to explore its effects on autophagy and apoptosis.GFP-LC3B adenovirus in-fection was observed under fluorescence microsco-py to assess LC3B expression.Autophagosomes were detected by transmission electron microscopy(TEM).LOX-1 mRNA levels were measured using re-al-time PCR.Protein expression of LOX-1,LC3Ⅱ/Ⅰ,Beclin-1,Atg5,cleaved-caspase 3,Bax,and Bcl-2 was analyzed by Western blot.Reactive oxygen spe-cies(ROS)levels were quantified using the DCFH-DA fluorescent probe.Apoptosis was assessed via Hoechst staining and flow cytometry(Annexin V-PI double staining).RESULTS:Hypoxia(1％O2,24 h)significantly increased LC3Ⅱ puncta under fluores-cence microscopy,upregulated LC3Ⅱ/Ⅰ protein ex-pression,and induced autophagosome formation observed by TEM.Hypoxia elevated ROS produc-tion and promoted apoptosis.LOX-1 mRNA and protein expression were upregulated in hypoxic HU-VECs.LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy,downregulating au-tophagy-related proteins(Beclin-1,Atg5,LC3Ⅱ/Ⅰ).LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis,as evidenced by decreased ex-pression of cleaved-caspase 3 and Bax,and in-creased Bcl-2 levels.CONCLUSION:Hypoxia in-duced upregulation of LOX-1 expression to produce ROS,thereby promoting autophagy and apoptosis in endothelial cells.

As phagocytic innate immune cells,macrophages interact with various tissue types and play an important role in immune defense,inflam-matory response and tissue remodeling.Macro-phages participate in the occurrence and develop-ment of disease by polarizing into classically acti-vated M1 type and substitutively activated M2 type,or more complex phenotypes,when the tis-sue microenvironment changes.This paper focused on the application of macrophage polarization in cardiovascular diseases,and introduces macro-phage origin and activation to propose the relation-ship between macrophage polarization and cardio-vascular diseases.Then,the strategies for targeted macrophage therapy were proposed to provide an important theoretical basis for improving the in-flammatory state of cardiovascular diseases.

AIM:To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)in hypoxia-induced autophagy and apopto-sis in endothelial cells.METHODS:Human umbili-cal vein endothelial cells(HUVECs)were exposed to hypoxia(1％O2)for varying durations(0,6,12,24 h)to evaluate autophagy and apoptosis levels.LOX-1 was further intervened to explore its effects on autophagy and apoptosis.GFP-LC3B adenovirus in-fection was observed under fluorescence microsco-py to assess LC3B expression.Autophagosomes were detected by transmission electron microscopy(TEM).LOX-1 mRNA levels were measured using re-al-time PCR.Protein expression of LOX-1,LC3Ⅱ/Ⅰ,Beclin-1,Atg5,cleaved-caspase 3,Bax,and Bcl-2 was analyzed by Western blot.Reactive oxygen spe-cies(ROS)levels were quantified using the DCFH-DA fluorescent probe.Apoptosis was assessed via Hoechst staining and flow cytometry(Annexin V-PI double staining).RESULTS:Hypoxia(1％O2,24 h)significantly increased LC3Ⅱ puncta under fluores-cence microscopy,upregulated LC3Ⅱ/Ⅰ protein ex-pression,and induced autophagosome formation observed by TEM.Hypoxia elevated ROS produc-tion and promoted apoptosis.LOX-1 mRNA and protein expression were upregulated in hypoxic HU-VECs.LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy,downregulating au-tophagy-related proteins(Beclin-1,Atg5,LC3Ⅱ/Ⅰ).LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis,as evidenced by decreased ex-pression of cleaved-caspase 3 and Bax,and in-creased Bcl-2 levels.CONCLUSION:Hypoxia in-duced upregulation of LOX-1 expression to produce ROS,thereby promoting autophagy and apoptosis in endothelial cells.

As phagocytic innate immune cells,macrophages interact with various tissue types and play an important role in immune defense,inflam-matory response and tissue remodeling.Macro-phages participate in the occurrence and develop-ment of disease by polarizing into classically acti-vated M1 type and substitutively activated M2 type,or more complex phenotypes,when the tis-sue microenvironment changes.This paper focused on the application of macrophage polarization in cardiovascular diseases,and introduces macro-phage origin and activation to propose the relation-ship between macrophage polarization and cardio-vascular diseases.Then,the strategies for targeted macrophage therapy were proposed to provide an important theoretical basis for improving the in-flammatory state of cardiovascular diseases.

Objective:To explore the impact of tislelizumab on renal function in bladder cancer patients with hydronephrosisMethods:A retrospective analysis of 34 bladder cancer patients with hydronephrosis treated at the Second Hospital of Tianjin Medical University from July 2020 to September 2023. Among them, 27 were male, and 7 were female, with an average age of (67.41±11.06)years and a body mass index (BMI) of (29.00±7.34) kg/m 2. 18 patients (52.9%) had hypertension, 5 (14.7%) had diabetes, and 5 (14.7%) had coronary heart disease. The baseline serum creatinine (SCr) was 81.15(69.18, 108.90)μmol/L, and the estimated glomerular filtration rate (eGFR) was 73.86(62.17, 91.12)ml/(min·1.73m 2). Of these, 26 patients (76.5%) had eGFR ≥60 ml/(min·1.73m 2)(G60+ group), and 8 patients (23.5%) had eGFR <60 ml/(min·1.73m 2)(G60- group). 10 patients (29.4%) had non-muscle invasive bladder cancer (NMIBC), and 24(70.6%) had muscle-invasive bladder cancer (MIBC). Eleven patients received surgical interventions within 1 month before baseline data collection that might affect hydronephrosis. All 34 patients received tislelizumab (200 mg, intravenous infusion every 3 weeks) combined with albumin-paclitaxel (200 mg, intravenous infusion every 3 weeks). Serum creatinine values were recorded before cycles 1, 2, and 3, and 21 days after cycle 3 (Cr1, Cr2, Cr3, CrE), and corresponding eGFR values (eGFR1, eGFR2, eGFR3, eGFRE) were calculated. A reduction in eGFR >25% from baseline at any of these points was defined as a decline in renal function (DRF), and an increase in eGFR >25% was defined as improvement in renal function (IRF). Differences in renal function changes and IRF, DRF incidence rates were compared between baseline subgroups Results:After 3 cycles of tislelizumab treatment, there was no significant change in eGFR []eGFR1 vs. eGFRE, 73.86 (62.16, 91.12)ml/(min·1.73m 2) vs. 83.82 (60.32, 90.62) ml/(min·1.73m 2), P=0.197]. Subgroup analysis showed that patients with diabetes had a significant increase in CrE compared to Cr1 (88.90 μmol/L vs. 69.40 μmol/L, P=0.043) and a significant decrease in eGFRE compared to eGFR1 [76.47 ml/(min·1.73m 2) vs. 87.73 ml/(min·1.73m 2), P=0.043]. No significant differences were observed in the other subgroups for SCr and eGFR within or between groups. DRF occurred in 4 patients (11.8%), with 1 diagnosed with acute renal injury, but not immune-related. IRF occurred in 8 patients (22.9%). In the subgroup analysis, the IRF incidence was significantly higher in the G60-group compared to the G60+ group (50.0% vs. 15.4%, P=0.044). No other factors were found to be associated with DRF or IRF. Conclusions:Tislelizumab treatment is safe for renal function in bladder cancer patients with hydronephrosis. Most patients with baseline poor renal function or underlying conditions like hypertension, diabetes, or coronary heart disease showed stable renal function during treatment.

Objective:To explore the impact of tislelizumab on renal function in bladder cancer patients with hydronephrosisMethods:A retrospective analysis of 34 bladder cancer patients with hydronephrosis treated at the Second Hospital of Tianjin Medical University from July 2020 to September 2023. Among them, 27 were male, and 7 were female, with an average age of (67.41±11.06)years and a body mass index (BMI) of (29.00±7.34) kg/m 2. 18 patients (52.9%) had hypertension, 5 (14.7%) had diabetes, and 5 (14.7%) had coronary heart disease. The baseline serum creatinine (SCr) was 81.15(69.18, 108.90)μmol/L, and the estimated glomerular filtration rate (eGFR) was 73.86(62.17, 91.12)ml/(min·1.73m 2). Of these, 26 patients (76.5%) had eGFR ≥60 ml/(min·1.73m 2)(G60+ group), and 8 patients (23.5%) had eGFR <60 ml/(min·1.73m 2)(G60- group). 10 patients (29.4%) had non-muscle invasive bladder cancer (NMIBC), and 24(70.6%) had muscle-invasive bladder cancer (MIBC). Eleven patients received surgical interventions within 1 month before baseline data collection that might affect hydronephrosis. All 34 patients received tislelizumab (200 mg, intravenous infusion every 3 weeks) combined with albumin-paclitaxel (200 mg, intravenous infusion every 3 weeks). Serum creatinine values were recorded before cycles 1, 2, and 3, and 21 days after cycle 3 (Cr1, Cr2, Cr3, CrE), and corresponding eGFR values (eGFR1, eGFR2, eGFR3, eGFRE) were calculated. A reduction in eGFR >25% from baseline at any of these points was defined as a decline in renal function (DRF), and an increase in eGFR >25% was defined as improvement in renal function (IRF). Differences in renal function changes and IRF, DRF incidence rates were compared between baseline subgroups Results:After 3 cycles of tislelizumab treatment, there was no significant change in eGFR []eGFR1 vs. eGFRE, 73.86 (62.16, 91.12)ml/(min·1.73m 2) vs. 83.82 (60.32, 90.62) ml/(min·1.73m 2), P=0.197]. Subgroup analysis showed that patients with diabetes had a significant increase in CrE compared to Cr1 (88.90 μmol/L vs. 69.40 μmol/L, P=0.043) and a significant decrease in eGFRE compared to eGFR1 [76.47 ml/(min·1.73m 2) vs. 87.73 ml/(min·1.73m 2), P=0.043]. No significant differences were observed in the other subgroups for SCr and eGFR within or between groups. DRF occurred in 4 patients (11.8%), with 1 diagnosed with acute renal injury, but not immune-related. IRF occurred in 8 patients (22.9%). In the subgroup analysis, the IRF incidence was significantly higher in the G60-group compared to the G60+ group (50.0% vs. 15.4%, P=0.044). No other factors were found to be associated with DRF or IRF. Conclusions:Tislelizumab treatment is safe for renal function in bladder cancer patients with hydronephrosis. Most patients with baseline poor renal function or underlying conditions like hypertension, diabetes, or coronary heart disease showed stable renal function during treatment.

Pulmonary hypertension (PH) is a rare and severe progressive disease. It results from hypertrophic remodeling of distal pulmonary arterioles that increases pulmonary arterial pressure and pulmonary vascular resistance in the absence of left heart, pulmonary parenchymal, or thromboembolic disease. Hypoxia-inducible factor-1 (HIF-1) regulates a large number of genes related to the occurrence and development of PH, and induces pulmonary angiogenesis, cell proliferation and migration, cellular energy metabolism and utilization. HIF-1 is an important component of the pathogenesis of hypoxic PH and plays an important role in driving the pathological process of pulmonary vascular and right ventricular remodeling. This article systematically elucidated the role and regulation of HIF-1 in hypoxic PH and its potential in targeted therapy of PH.