OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

Objective To analyze the therapeutic effects and survival benefits of sintilimab combined with albumin-bound paclitaxel chemotherapy in the treatment of patients with advanced gastric cancer.Methods Patients with advanced gastric cancer were divided into the treatment group and the control group by cohort method.The control group was treated with albumin-bound paclitaxel-based chemotherapy[intravenous infusion of albumin-bound paclitaxel at 125 mg·m-2 from day 1 to day 8,for a cycle(21 days as a cycle);Tiggio capsule 40 mg·m-2·d-1 was taken orally for 1-14 days for 1 consecutive cycle;Trastuzumab was administered once every 3 weeks at an initial loading dose of 8 mg·kg-1,followed by maintenance treatment at a dose of 6 mg·kg-1 every 3 weeks].On this basis,the treatment group was treated with intravenous infusion of sintilimab injection at a dose of 200 mg·time-1 on the first day of each cycle,with 21 d as a cycle.After 6 cycles of continuous treatment,both groups were given maintenance treatment and were followed up for 8 months.The two groups were compared in terms of clinical efficacy,the levels of serum tumor markers[carbohydrate antigen 242(CA242),carbohydrate antigen 724(CA724),carcinoembryonic antigen(CEA),tissue polypeptide-specific antigen(TPS),soluble intercellular cell adhesion molecule-1(sICAM-1)and E-cadherin],survival and evaluated the safety.Results In this study,39 and 41 patients were enrolled in the control group and the treatment group,respectively.At the end of treatment,the objective response rates(ORR)in the treatment group and the control group were 56.10％and 33.33％;the disease control rates(DCR)were 78.05％and 48.71％.The differences were statistically significant(all P＜0.05).After treatment,serum CA242 levels in the treatment group and the control group were(57.64±5.82)and(68.95±7.23)mg·L-1;CA724 levels were(36.58±3.79)and(43.65±4.48)U·mL-1;CEA levels were(17.33±1.78)and(20.16±2.35)ng·mL-1;TPS levels were(21.35±2.44)and(37.65±3.84)U·L-1;sICAM-1 levels were(216.77±22.53)and(275.34±28.63)ng·mL-1;E-cadherin levels were(12.15±1.36)and(9.87±1.45)ng·mL-1.The differences were statistically significant(all P＜0.05).The average progression free survival(PFS)of the treatment group and the control group was 7.55 months and 7.17 months;PFS rates were 65.78％and 56.42％.The differences were statistically significant(P＜0.05).The adverse drug reactions in the treatment group and the control group were mainly bone marrow suppression,nausea and vomiting,liver function damage,peripheral nerve paresthesia,and hypothyroidism.There was no statistically significant difference in the above adverse drug reactions between the treatment group and the control group(all P＞0.05).Conclusion Sintilimab combined with albumin-bound paclitaxel chemotherapy is effective in the treatment of patients with advanced gastric cancer,which can significantly improve serum tumor markers and prolong PFS,with good safety.

Fourteen compounds were isolated from the n-butanol fraction of the 95% aqueous ethanol extract of the stems and twigs of Strychnos cathayensis by D101 macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography, and semipreparative RP-HPLC. Their structures were elucidated as ethyl 4-O-β-D-allopyranosyl-vanillate (1), n-butyl 4-O-β-D-allopyranosyl-vanillate (2), n-butyl 4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillate (3), n-butyl 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillate (4), n-butyl 4-O-(6′-O-syringoyl)-β-D-glucopyranosyl-vanillate (5), n-butyl 4-O-α-L-rhamnopyranosyl-syringate (6), methyl 3-methoxy-4-(β-D-allopyranosyloxy) benzoate (7), pseudolaroside B (8), butyl syringate (9), glucosyringic acid (10), methyl syringate (11), methyl 4-hydroxy-3-methoxybenzoate (12), clemochinenoside C (13), and clemoarmanoside A (14), respectively, on the basis of spectroscopic data interpretation and by comparison with literature information. Compounds 1-6 are artificial products of phenolic acid esterified by ethanol or n-butanol. It is noted that the precursors (4-O-(6′-O-syringoyl)-β-D-allopyranosyl-vanillic acid and 4-O-(6′-O-vanilloyl)-β-D-allopyranosyl-vanillic acid) of compounds 3 and 4 are new compounds. The hepatoprotective, anti-inflammatory, antioxidant and cytotoxic activities of compounds 1-13 were evaluated in vitro at a concentration of 10 μmol·L^-1. Compounds 1, 2 and 6-10 exhibited potential hepatic protection effects with cell survival rates ranging from 53.6% to 55.5% (acetaminophen, 45.4% at 8 mmol·L^-1). Compound 4 demonstrated anti-inflammatory activity with nitric oxide inhibitory rate of 74.6%. Compounds 3 and 5 showed potential antioxidant activities with malondialdehyde inhibitory rates of 53.2% and 56.1%, respectively.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS). METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS). RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01). CONCLUSIONS Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.
Coronary Angiography ; Coronary Artery Disease/diagnostic imaging* ; Coronary Vessels/pathology* ; Cross-Sectional Studies ; Humans ; Medicine, Chinese Traditional ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Syndrome ; Ultrasonography, Interventional/methods*

Objective:To investigate the availability and safety of a domestic disposable digital flexible cystoscope compared with a reusable Olympus digital flexible cystoscope in cystoscopy and removal of double J stent.Methods:From August 2018 to March 2019, patients were enrolled in this prospective, open, multicenter, randomized, parallel positive controlled clinical trial study, which were from department of Urology in Renmin Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University and the First Affiliated Hospital of Guangzhou Medical University. The experimental group and control group were assigned into a 1∶1 ratio by random table method. Inclusion criteria included age≥18 years and have indications for cystoscopy or removal of double J stent. Exclusion criteria included patients having acute genitourinary tract infection, having tuberculous bladder contracture, bladder capacity less than 50ml, having urethrostenosis, female menstrual period, pregnancy and lactation, having difficulty for lithotomy position, having serious cardio-cerebrovascular disease and liver or kidney dysfunction. A domestic disposable digital flexible cystoscope was adopted in the experimental group, whereas a reusable Olympus digital flexible cystoscope was used in the control group. Acceptability of image was defined as primary availability indicator, while success rate of working and performance score were defined as secondary availability indicators and mean operating time was calculated for cystoscopy only and cystoscopy plus removal of double J stent respectively, yet rate of adverse event as well as rate of equipment defects were sorted as safety indicators.Results:A total of 188 cases which were listed in per protocol set completed the clinical trial study successfully. There were 95 cases in the experimental group and 93 cases in the control group. Acceptability of image was 93.68%(89/95) and 96.77%(90/93) respectively in two groups( P=0.52). Success rate of working was 100.00%(95/95) and 98.92%(92/93) respectively in two groups ( P=0.49). Performance score was 14.41±0.93 and 14.56±0.84 respectively in two groups ( P=0.23). Mean operating time (MOT) only for cystoscopy was (15.3±2.6) min and (15.4±3.3)min respectively in two groups ( P=0.93), while MOT for cystoscopy plus removal of double J stent was (21.0±3.2) min and (21.7±3.9) min respectively in two groups ( P=0.69). Rate of adverse event was 8.42%(8/95) and 9.68%(9/93) respectively in two groups( P=0.76). There was no equipment defects in both groups. Conclusions:There is no statistical difference in acceptability of image, success rate of working, performance score, mean operating time for cystoscopy or removal of double J stent, rate of adverse events and rate of equipment defects. A domestic disposable digital flexible cystoscope has shown non-inferiority in the availability and safety compared with a reusable Olympus digital flexible cystoscope.

Objective: To investigate the effect of visceral fat area (VFA) on the surgical efficacy and early postoperative complications of radical gastrectomy for gastric cancer. Methods: A retrospective cohort study method was used. Clinicopathological data and preoperative imaging data of 195 patients who underwent D2 radical gastric cancer surgery at the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to December 2017 were analyzed retrospectively. Inclusion criteria: (1) complete clinicopathological and imaging data; (2) malignant gastric tumor diagnosed by preoperative pathology, and gastric cancer confirmed by postoperative pathology; (3) no preoperative complications such as bleeding, obstruction or perforation, and no distant metastasis. Those who had a history of abdominal surgery, concurrent malignant tumors, poor basic conditions, emergency surgery, palliative resection, and preoperative neoadjuvant therapy were excluded. The VFA was calculated by software and VFA ≥ 100 cm² was defined as visceral obesity according to the Japan Obesity Association criteria . The patients were divided into high VFA (VFA-H, VFA≥100 cm², n=96) group and low VFA (VFA-L, VFA<100 cm², n=99) group . The clinicopathological characteristics, surgical outcomes and early postoperative complications were compared between the two groups. Univariate and multivariate Logistic regression models were used to analyze the risk factors of early complications. Receiver operating characteristic (ROC) curve was used to analyze predictive values of VFA for early complications. Pearson's χ² test was used to analyze the correlation between BMI and VFA. Results: There were no significant differences in terms of gender, age, American Society of Anesthesiologists physical status classification, preoperative comorbidities, preoperative anemia, tumor TNM staging, N staging, T staging and tumor differentiation, surgical method, extent of resection, and tumor location between the VFA-L group and the VFA-H group (all P>0.05). However, patients in the VFA-H group had higher BMI, larger tumor, lower rate of hypoalbuminemia and greater subcutaneous fat area (SFA) (all P<0.05). The VFA-H group presented significantly longer operation time and significantly less number of harvested lymph nodes as compared to the VFA-L group (both P<0.05). However, there were no significant differences in intraoperative blood loss, conversion to laparotomy and postoperative hospital stay (all P>0.05). Complications of Clavien-Dindo grade II and above within 30 days after operation were mainly anastomosis-related complications (leakage, bleeding, infection and stricture), intestinal obstruction and incision infection. The VFA-H group had a higher morbidity of early complications compared to the VFA-L group [24.0% (23/96) vs 10.1% (10/99), χ²=6.657, P=0.010], and the rates of anastomotic complications and incision infection were also higher in the VFA group [10.4% (10/96) vs. 3.0% (3/99), χ²=4.274, P=0.039; 7.3% (7/96) vs. 1.0% (1/99), P=0.033]. Multivariate logistic analysis showed that high BMI (OR=3.688, 95%CI: 1.685-8.072, P=0.001) and high VFA (OR=2.526, 95%CI: 1.148-5.559,P=0.021) were independent risk factors for early complications. The area under the ROC curve (AUC) of VFA for predicting early complications was 0.645, which was higher than that of body weight (0.591), BMI (0.624) and SFA (0.626). Correlation analysis indicated that there was a significantly positive correlation between BMI and VFA (r=0.640, P<0.001). Conclusion: VFA ≥ 100 cm² is an independent risk factor for early complications after radical gastrectomy for gastric cancer.It can better predict the occurrence of above early postoperative complications.
Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Lipids ; Obesity/surgery* ; Obesity, Abdominal/surgery* ; Postoperative Complications/epidemiology* ; Retrospective Studies ; Stomach Neoplasms/pathology*

Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.
Albumins ; Anastomosis, Roux-en-Y/adverse effects* ; Cholesterol ; Gastrectomy/methods* ; Hemoglobins ; Humans ; Laparoscopy/methods* ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Treatment Outcome ; Vitamin B 12

Dysmenorrhea is a common gynecological disease in clinic， with primary dysmenorrhea and secondary dysmenorrhea. Primary dysmenorrhea is usually not accompanied by organic lesions in genital organs， which is mainly related to the increase of prostaglandin content in endometrium during menstruation. Secondary dysmenorrhea is accompanied by organic lesions of reproductive organs， often associated with local lesions of reproductive organs， but also with patients' mental factors and neuroendocrine factors.The incidence of dysmenorrhea is as high as 73.8%， and there is no radical cure method， which has a great impact on the life， work and learning of patients. Chinese medicine essential oil widely exists in aromatic Chinese medicine， with antibacterial， antioxidant and anticancer activities. It can regulate neuroendocrine function， anti-inflammatory and analgesic effects， and improve mood by regulating the levels of prostaglandins， oxytocin and other hormones in the body and regulating the emotions of patients， there by alleviating dysmenorrhea to a certain extent. In recent years， many scholars have made more in-depth research on Chinese medicine essential oil in alleviating dysmenorrhea， but there is a lack of comprehensive collation of such studies. In this regard， the author has systematically sorted out the generation and classification of dysmenorrhea， the mechanism of action of essential oil of traditional Chinese medicine to alleviate dysmenorrhea and the application of essential oil of traditional Chinese medicine in the field of dysmenorrhea by consulting relevant literature in Chinese and foreign languages in recent years， so as to provide reference for the treatment of dysmenorrhea.