OBJECTIVE: To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP). METHODS: The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot. RESULTS: In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01). CONCLUSION Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
Abietanes/therapeutic use* ; Osteosarcoma/enzymology* ; Cisplatin/therapeutic use* ; Humans ; Cell Line, Tumor ; Animals ; Apoptosis/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MAP Kinase Signaling System/drug effects* ; Bone Neoplasms/enzymology* ; Cell Cycle/drug effects* ; Xenograft Model Antitumor Assays ; Mice ; Drug Resistance, Neoplasm/drug effects* ; Neoplasm Invasiveness ; Mice, Inbred BALB C

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

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100％in both groups,and that of anastomosis leakage after VE was 16.7％in the experimental group and 14.3％in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P＜0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P＜0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P＜0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.

Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC₅₀ as 4.77, 1.59, 11.11 and 25.87 μmol·L^-1, resepectively.

Two new labdane diterpenoids were isolated from 95% ethanol extract of the leaves of Callicarpa formosana Rolfe by using silica gel column, MCI column, ODS column and HPLC. Their structures were elucidated by HR-ESI-MS, NMR and ECD spectral data. All of them are new compounds, named 13E-6β-hydroxylabda-8(17),13-dien-15-oic acid (1) and 13E-7α-hydroxylabda-8(17),13-dien-15-oic acid (2). Compounds 1 and 2 were tested for antioxidant activity, and none of them had obvious activity.

In this paper, the micro-video teaching mode was explored in the course construction of . The micro-video teaching contents include the academic thought, experience in diagnosis and treatment, characteristic technology and clinical manipulation of famous acupuncture experts in the Henan University of CM. Each micro-video film is designed within 15-18 min, including three sections of knowledge, i.e. basic theory, technological application and clinical manipulation. Each section is designed within 5-6 min. The construction of the teaching course of is the innovation of practice mode of TCM and the new approach to the inheritance of the experience of experts. The construction of micro-video teaching course propels the reform of teaching mode, improves the learning initiative of students and clinical manipulative ability so as to improve the teaching effect and quality.
Acupuncture Therapy ; Humans ; Learning ; Moxibustion ; Students ; Teaching

Objective To observe the clinical efficacy of acupuncture plus medication in treating chronic pelvic inflammatory disease. Method By using the random number table, sixty-eight patients with chronic pelvic inflammatory disease were randomized into an acupuncture-medication group of 34 cases and a medication group of 34 cases. The clinical efficacies were compared after 2 courses of treatment, and the symptoms and body signs scores and syndrome score of traditional Chinese medicine (TCM) were also compared. Result There was a significant difference in comparing the therapeutic efficacy between the acupuncture-medication group and the medication group (P<0.05). After the treatment, the symptoms and body signs scores and TCM syndrome score dropped significantly in both groups (P<0.05), indicating that the two groups both had improvement in the symptoms, body signs and TCM syndrome; there were significant between-group differences in comparing the score differences in the symptoms and body signs scores and TCM syndrome score after the treatment (P<0.05), and the acupuncture-medication group was higher than the medication group. Conclusion Acupuncture plus medication can better ameliorate the symptoms and body signs and TCM syndrome in chronic pelvic inflammatory disease.

Background:Renal cell carcinoma (RCC) is frequently associated with paraneoplastic inflammatory syndrome (PIS). This study aimed at exploring the connections between the survival rate and specific gene alterations and the potential mechanism.

Methods:We retrospectively studied 69 surgical RCC cases from August 2014 to February 2016, including 18 cases of clear cell RCC (ccRCC) demonstrating elevated pretreatment serum C-reactive protein (CRP, Group A). Twelve of the 18 cases were symptomized with febrile episode. We also selected 49 cases of ccRCC with normal pretreatment CRP (Group B). Using 22 microsatellite markers, we compared the incidence of loss of heterozygosity (LOH) between Group A and Group B. All statistical tests are two-sided.

Results:The 3p LOH was common in both Group A (89%) and Group B (92%). The frequency of 14q LOH in Group A (16 of 18) was higher than Group B (4 of 49, χ= 40.97 P < 0.0001). The 3p and 14q LOH were the characteristics of ccRCC with elevated acute phase reactants, including PIS, regardless of the presence of metastasis. On the contrary, 14q LOH was a rare genomic alternation in advanced-staged ccRCC without PIS. The overall survival of patients with elevated CRP (33.3%) was lower than its counterparts (6.1%, hazard ratio=1.852, P < 0.0001) in Kaplan-Meier curve.

Conclusions:The results imply that the disruption of a 14q gene(s) might result in not only the inflammatory manifestations in the tumor host but also the poor survival rate as well. The isolation of the gene(s) on 14q might be a vital goal in the treatment of PIS-associated RCC.

Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1), gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg^-1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg·kg^-1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).