Vascular endothelial growth factor (VEGF) inhibitors are drugs that target and inhibit tumor angiogenesis. By blocking the signaling pathway of VEGF and its receptor, they suppress tumor proliferation and play a crucial role in tumor treatment. However, their side effects, such as hypertension, proteinuria, hand-foot skin reactions, and myelosuppression, during treatment seriously affect patients' treatment compliance and quality of life. The development of intervention strategies for the side effects of VEGF inhibitors is of great importance for tumor treatment. This article reviews the clinical characteristics and toxic mechanisms of common side effects caused by VEGF inhibitors during tumor treatment and summarizes intervention strategies that combine traditional Chinese and Western medicines. Drug dosages were precisely monitored and adjusted to achieve antitumor treatment. Patients' discomfort symptoms are improved through prescriptions that act by tonifying qi and promoting blood circulation, strengthening the spleen, and tonifying the kidney. The combination of traditional Chinese and Western medicines is used to treat patients, thus providing a safe and effective treatment plan for patients with cancer.

This paper systematically reviews the current status of integrated traditional Chinese and western medicine in the treatment of Helicobacter pylori （Hp） infection， as well as recent progress in clinical and basic research both in China and internationally. It summarizes the advantages of traditional Chinese medicine （TCM） in Hp infection management， including improving Hp eradication rates， enhancing antibiotic sensitivity， reducing antimicrobial resistance， decreasing drug-related adverse effects， and ameliorating gastric mucosal lesions. These advantages are particularly evident in patients who are intolerant to bismuth-containing regimens， those with refractory Hp infection， and individuals with precancerous gastric lesions. An integrated， whole-process management approach and individualized， staged comprehensive treatment strategies combining TCM and western medicine are proposed for Hp infection. Future prevention and control of Hp infection should adopt an integrative Chinese-western medical strategy， emphasizing prevention， strengthening primary care， implementing proactive long-term monitoring， optimizing screening strategies， and advancing the development of novel technologies and mechanistic studies of Chinese herbal interventions. These efforts aim to provide a theoretical basis and practical pathways for the establishment and improvement of Hp infection prevention and control systems.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Objective:To investigate the impact of receptor-interacting protein kinase 3 (RIPK3) on major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI), as well as the predictive performance of RIPK3 combined with traditional cardiovascular risk factors.Methods:This study was a single-center prospective cohort study. It included patients with AMI who underwent PCI at Peking Union Medical College Hospital between September 2017 and November 2017. Baseline clinical data were collected, and plasma samples were obtained 6 hours after PCI to measure RIPK3 levels. Follow-up was conducted via outpatient visits or phone calls to record the occurrence of MACE, including cardiovascular death, hospitalization for heart failure, and vascular events (recurrent AMI or stroke). The predictive performance of RIPK3, traditional cardiovascular risk factors and their combination for MACE was compared using receiver operating characteristic (ROC) curves. Patients were divided into low- and high-RIPK3 level groups based on the optimal cutoff value of RIPK3. Multivariate Cox proportional hazards regression analysis was used to assess the impact of RIPK3 levels on MACE after PCI in AMI patients. Kaplan-Meier survival curves were plotted, and the log-rank test was used to compare MACE incidence between the low-and high-RIPK3 groups.Results:A total of 103 AMI patients who underwent PCI were included, aged 63.0 (56.0, 69.0) years, and 83 (80.6%) were male. The follow-up time was 5.17 (2.81, 5.17) years, during which 44 patients (42.7%) experienced MACE. The ROC curve analysis showed that the area under the curve ( AUC) for traditional cardiovascular risk factors was 0.68 (95% CI: 0.58-0.78), while the AUC for plasma RIPK3 was 0.72 (95% CI: 0.62-0.82). The combined AUC for traditional risk factors and RIPK3 was 0.75 (95% CI: 0.65-0.85). Multivariate Cox proportional hazards regression analysis indicated that plasma RIPK3 level is greater than or equal to the optimal cutoff value of 440.9 μg/L ( HR=3.31, 95% CI: 1.53-8.30, P=0.005) was an independent risk factor for MACE in AMI patients after PCI. Kaplan-Meier survival analysis demonstrated that the high-RIPK3 group had a significantly higher risk of MACE after PCI compared to the low-RIPK3 group (log-rank P=0.006). Conclusions:Elevated plasma RIPK3 level is an independent risk factor for MACE in AMI patients after PCI. Plasma RIPK3 combined with traditional cardiovascular risk factors can more effectively predict the occurrence of MACE in AMI patients after PCI. AMI patients with RIPK3≥440.9 μg/L have a higher risk of MACE after PCI.

Background:Acute pancreatitis(AP)is a common clinical gastrointestinal emergency with a high mortality rate.Intestinal dysfunction is one of the common complications of AP and can aggravate the disease condition.Therefore,early and accurate assessment of the disease severity and intestinal dysfunction of AP is of great significance for improving the prognosis of patients.Aims:To investigate the correlation of early serum levels of interleukin-1β(IL-1β),C-reactive protein(CRP),endotoxin(ET),D-lactic acid(D-LA),and diamine oxidase(DAO)with disease severity and intestinal dysfunction in AP patients.Methods:A total of 52 AP patients admitted to the Second Affiliated Hospital of Baotou Medical College from September 2023 to September 2024 were enrolled,and 10 healthy individuals recruited during the same period were served as the control group.AP patients were classified into mild acute pancreatitis(MAP),moderately severe acute pancreatitis(MSAP)and severe acute pancreatitis(SAP)groups according to the severity of the disease.Intestinal function was evaluated using the acute gastrointestinal injury(AGI)grading system.ELISA was used to detect the early serum levels of IL-1β,CRP,ET,D-LA,and DAO,and the correlation of these indicators with the severity of AP and AGI grade were analyzed by Spearman correlation coefficient.Results:Serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MAP,MSAP,and SAP groups were significantly higher than those in the control group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the MSAP group were significantly higher than those in the MAP group(all P<0.05);serum levels of IL-1β,CRP,ET,D-LA,and DAO in the SAP group were significantly higher than those in the MAP and MSAP groups(all P<0.05).Compared with AGI grade 0-Ⅰ subjects,serum levels of IL-1β,CRP,ET,D-LA,and DAO in patients with AGI grade Ⅱ,Ⅲ and Ⅳ were significantly increased(all P<0.05).Compared with AGI grade Ⅱ patients,serum D-LA level in patients with AGI grade Ⅲ was significantly increased(P<0.05).Compared with AGI grade Ⅲ patients,serum D-LA level in patients with AGI grade Ⅳ was significantly increased(P<0.05).Serum levels of IL-1β,CRP,ET,D-LA,and DAO were positively correlated with the severity of AP and AGI grade(all P<0.05).Conclusions:Early serum levels of IL-1β,CRP,ET,D-LA,and DAO in AP patients are significantly increased and closely related to the disease severity and intestinal dysfunction.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

BACKGROUND:The cryopreservation technology enables tissues/cells to be stored for a long time in a low-temperature environment while maintaining the integrity of their activity and function,which is of great significance for the construction of cell therapy,tissue engineering and biological sample banks.Cryoprotective agents often contain dimethyl sulfoxide and serum.To avoid the toxic side effects of dimethyl sulfoxide,the complexity of serum components and immune responses,although some finished cryoprotective agents have been marketed,they are faced with many difficulties such as high cost and limited application.Therefore,there is an urgent need to develop a cryoprotective agent with clear components and the ability to solve the above problems.OBJECTIVE:To evaluate the effects of a novel cryoprotectant on cryopreservation efficiency of different tissue and cell sources.METHODS:By applying the novel cryoprotectant as an experimental group with the commercially available and widely used cryoprotectant(control group)to umbilical cord Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,NK and CIK cells,comparative analyses were conducted in terms of cell morphology,number,viability,surface markers,differentiation potential,and cell-killing toxicity assay before cryopreservation and after resuscitation thawing.We confirmed the cryopreservation effect of the new cryoprotectant and its potential application value.RESULTS AND CONCLUSION:(1)The novel cryoprotectant facilitated the normal growth of cryopreserved Wharton's jelly tissue upon recovery,exhibiting mesenchymal stem cell morphology.No significant differences were observed between the experimental and control groups in terms of cell recovery rate,surface markers,and differentiation potential.(2)There was no significant difference in the number and viability of cells between the experimental group and the control group after cryopreservation of cord blood/peripheral blood mononuclear cells,and the cryo-resuscitated cell numbers and viability of derived NK cells/CIK cells did not show significant difference between the experimental and control groups.(3)For NK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportion of CD56+CD16+cell subpopulations between the experimental group and the control group.For CIK cells derived and differentiated from cord blood/peripheral blood mononuclear cells,there was no significant difference in the proportions of CD3+CD8+and CD3+CD56+cell subpopulations between the experimental group and the control group.(4)In terms of cytotoxicity testing,when the effective-target ratio of immune cells and melanoma cell line Mel624 was 20:1,whether it was NK cells/CIK cells derived from cord blood or peripheral blood mononuclear cells,there was no significant difference in the tumoricidal activity of cells between the experimental group and the control group.These findings suggest that the novel cryoprotectant can replace existing commercially available and widely used cryoprotectants,and is applicable to Wharton's jelly tissue,umbilical cord mesenchymal stem cells,umbilical cord blood/peripheral blood mononuclear cells,as well as NK and CIK cells,providing a solid technical foundation for the scaling,standardization,and commercialization of universal cryoprotectants.

Objective To explore the value of MRI subtraction technique(ST)for evaluating the efficacy of systemic therapy for advanced hepatocellular carcinoma(HCC)and predicting prognosis after combining with surgery.Methods Totally 35 patients with 39 HCC lesions who received systemic therapy+radical resection were retrospectively collected.Based on preoperative MRI,tumor activity ratio(recorded as tumor activityST)was obtained with ST,while tumor activity value(recorded as tumor activitypathology)was obtained through postoperative pathology,and their correlation was analyzed.The patients were regularly followed up after surgery,and the survival data were recorded.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of tumor activityST for predicting patients'survival status.Then the patients were divided into survival benefit group and no survival benefit group according to the cut-off value,and survival analysis was conducted.Results Tumor activityST was positively correlated with tumor activitypathology(r=0.900,P＜0.001).The median follow-up time was 32.93 months,during which 8 patients died,and the median survival time was 29.9 months.The area under the curve(AUC)of tumor activityST for predicting patients'survival status was 0.67,and the cut-off value was 0.36.Thirty patients with tumor activityST＜0.36 were enrolled in survival benefit group,while 5 patients≥0.36 were collected in no survival benefit group.The overall survival in survival benefit group was longer than that in no survival benefit group(P＜0.001).Conclusion MRI ST could be used to non-invasively evaluate the efficacy of systemic therapy for advanced HCC and predict prognosis after combining with surgery.

Objective : To explore the effect of Wilms′ tumor 1-associated protein(WTAP) on tissue collagen deposition in pulmonary fibrosis caused by bleomycin. Methods : 60 mice were randomly divided into four groups: control group(Control group), Bleomycin-induced pulmonary fibrosis group(BLM group), pulmonary fibrosis lentivirus empty vector control group(BLM+LV-NC group), pulmonary fibrosis WTAP lentivirus group virus group(BLM+LV-WTAP group). Experimental pulmonary fibrosis mouse model was established by subcutaneous injection of bleomycin(35 mg/kg) into the abdomen, twice a week for a total of 8 times. After modeling, Western Blot was used to detect the protein expression of fibrosis-related markers α-smooth muscle actin(α-SMA), type I collagen(Collagen Ⅰ), fibronectin(Fibronectin), and WTAP protein. Masson staining and Sirius Red staining were used to detect collagen deposition. RT-qPCR was used to detect WTAP mRNA expression, WTAP lentivirus infection effect, and Collagen Ⅰ mRNA expression. Results: Compared with the Control group, the expression of pulmonary fibrosis markers α-SMA(P<0.001), Collagen Ⅰ(P<0.001), and Fibronectin(P<0.01) protein in the BLM group all increased. Masson staining(P<0.001) and Sirius Red staining(P<0.001) confirmed that significant collagen deposition occurred in the lung tissue of the BLM group. In addition, the expression of WTAP protein in the lung tissue of the BLM group increased(P<0.01). Compared with the Control group, the expression of WTAP mRNA in the BLM group increased(P<0.001). Compared with the BLM+LV-NC group, the expression of WTAP mRNA in the tissues of the BLM+LV-WTAP group decreased(P<0.001), proving that virus infection is effective. After infection with WTAP lentivirus, collagen fiber deposition decreased(P<0.001), Collagen Ⅰ mRNA(P<0.001) level decreased, and protein(P<0.001) expression decreased in the BLM+LV-WTAP group. Conclusion Knocking down of WTAP can reduce collagen deposition in bleomycin-induced pulmonary fibrosis tissue in mice and improve experimental pulmonary fibrosis.

Objective: To investigate the effect of sirtuin 2(SIRT2) on the proliferation and migration of cardiac fibroblasts(CFs)in C57BL/6 mice under angiotensin II(Ang Ⅱ) stimulation. Methods : The hearts were taken from 1 to 2 days C57BL/6 milk mice. After cutting and digesting, CFs were extracted by different adhesion centrifugation. After CFs attachment, the cells were cultured under control medium and Ang Ⅱ(100 nmol/L) medium and treated using OE-SIRT2 plasmid to overexpression the SIRT2 gene. RT-qPCR was used to detect mRNA expression of SIRT2 proliferating cell nuclear antigen(PCNA), periostin(POSTN)and type Ⅰ collagen procollagen A1(Col1A1), Western blot assay was used to measure the protein expression levels of SIRT2, PCNA, POSTN and Col1A1, CCK-8 assay and EdU assay were used to evaluate CFs proliferation rate, Transwell experiment was used to assess CFs migration activity. Results: Compared with control group, Ang Ⅱ stimulation led to down-regulation of SIRT2 expression in CFs, increased collagen expression, and promoted CFs proliferation and migration. The expression of SIRT2 was up regulated in CFs treated with OE-SIRT2 plasmid under Ang Ⅱ stimulation, Col1A1, POSTN and PCNA expression was down regulated, and CFs proliferation and migration ability decreased. Conclusion Overexpression of SIRT2 can inhibit the proliferation and migration of CFs under Ang Ⅱ stimulation, indicating that SIRT2 may be a key regulatory point in the onset and progression of cardiac fibrosis.