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.

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.

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.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

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.

In recent years, obesity has become a global public health problem, and the incidence of obesity among children and adolescents in China has been gradually increasing.Obesity in childhood will affect the development and health of children and may lead to an increased incidence of multiple chronic diseases in adulthood.The current main strategy for weight reduction in obese children is to change their dietary habits and increase physical activity, but it is prone to relapseand has a high failure rate.Obese patients exhibit persistent hunger and lack of satiety.Glucagon-like peptide-1 receptor agonists, which suppress appetite and increase satiety, have successfully treated adult obesity with good results.This article will discuss the feasibility and safety of using glucagon-like peptide-1 receptor agonists for obesity in children and adolescents by reviewing the possible mechanisms of action of glucagon-like peptide-1 receptor agonists for weight reduction and the clinical data of glucagon-like peptide-1 receptor agonists on obesity in children and adolescents.