The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

The chemical constituents of Commiphora myrrha was investigated by column chromatography on silica gel, ODS, Sephadex LH-20, and semi-preparative HPLC. Their structures were elucidated by comprehensive spectroscopic methods including UV, IR, MS, NMR, as well as ECD calculation. Seven compounds were isolated from the dichloromethane-soluble fraction of C. myrrha and their structures were identified as(1S,2R,4S,5R,8S)-guaiane-2-hydroxy-7(11),10(15)-dien-6-oxo-12,8-olide(1), commipholide E(2), myrrhterpenoid H(3), myrrhterpenoid I(4), myrrhterpenoid E(5), 2α-methoxy-8α-hydroxy-6-oxogermacra-1(10),7(11)-dien-8,12-olide(6), 8,12-epoxy-1α,9α-hydroxy-eudesma-7,11-diene-6-dione(7). Compound 1 was a new compound and named myrrhterpenoid P. Compound 7 was isolated from Commiphora genus for the first time. Compounds 2, 5, and 6 significantly inhibited nitric oxide(NO) production in LPS-stimulated RAW264.7 cells, with IC_(50) values of(49.67±4.16),(40.80±1.27),(47.22±0.87) μmol·L~(-1), respectively [indomethacin as the positive control, with IC_(50) value of(63.92±2.60) μmol·L~(-1)].
Commiphora/chemistry* ; Animals ; Mice ; Resins, Plant/chemistry* ; Sesquiterpenes/isolation & purification* ; Molecular Structure ; Nitric Oxide ; Macrophages/metabolism* ; RAW 264.7 Cells ; Drugs, Chinese Herbal/pharmacology*

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

This study aims to systematically review and evaluate the quality of clinical research on the treatment of adenomyosis(AM) with traditional Chinese medicine(TCM) in recent ten years, using evidence graphs. Computer searches were conducted on eight Chinese and English databases, commonly used guideline databases, and guideline-related websites, covering the period from January 1, 2014, to October 1, 2024. Two researchers independently screened, extracted information, and evaluated the quality of the evidence. The distribution and quality of the clinical research evidence were presented using both text and charts. A total of 565 articles were included in the study, comprising 523 intervention studies, 23 observational studies, 18 systematic reviews/Meta-analysis, and 1 guideline. The overall publication volume has shown a downward trend in past two years. The sample sizes of the intervention and observational studies primarily focused on 60 to 120 cases. The intervention schemes mainly involved multi-therapy combinations, including 33 classic prescriptions and 25 Chinese patent medicines. Among these, 48 studies related to 17 classic prescriptions and 45 studies related to 10 types of Chinese patent medicines involved TCM syndrome types. Randomized controlled trial(RCT) tended to focus on overall clinical efficacy and the degree of dysmenorrhea as key outcome measures. Methodological quality issues were found in 97 RCTs related to TCM decoctions and 131 RCTs related to Chinese patent medicines, primarily involving unclear explanations of some information. The AMSTAR scores for the 18 systematic reviews/Meta-analysis ranged from 1 to 8 points, with 16 studies suggesting "evidence of potential therapeutic efficacy". The recommended level for the one included guideline was B-level. TCM shows significant advantages in treating AM. Future clinical research should further standardize study designs, reference relevant reporting guidelines, improve the quality of clinical research, generate higher-level evidence-based results, and promote the high-quality development of clinical research on TCM for treating AM.
Humans ; Adenomyosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

OBJECTIVES: To evaluate the one-year outcomes of valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) using SAPIEN 3 valve for treating mitral bioprosthetic valve failure. METHODS: A retrospective analysis was conducted on 26 patients with mitral bioprosthetic valve failure who underwent ViV-TMVR at West China Hospital, Sichuan University, between November 2022 and July 2024. The age of patients was 71.5 (64.5, 74.5) years, and 69.2% were female. Bioprosthetic valve failure occurred at (9.7±3.7) years after initial surgical implantation, with the most common failure mode being mixed stenosis and regurgitation (53.8%). The SAPIEN 3 valve was implanted via either a transseptal or transapical approach. Echocardiography was performed preoperatively, immediately post-procedure, and at 1 month, 6 months, and 1 year post-procedure. Outcomes included all-cause mortality, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score, and postoperative complications. RESULTS: The procedure was performed via the transseptal approach in 21 patients (80.8%) and the transapical approach in 5 patients (19.2%). All procedures were technically successful. No paravalvular leakage was observed immediately post-procedure, and mitral valve hemodynamics improved significantly. At the 1-year follow-up, 2 patients had died. Two patients (8.3% of survivors) were of NYHA functional class Ⅲ, and KCCQ-12 score improved to (88.4±14.6) points (both P<0.01). Echocardio-graphy at 1 year postoperatively showed significant reductions in peak mitral valve velocity [to (2.29±0.32) m/s] and mean transvalvular pressure gradient [to (9.5±3.5) mmHg, 1 mmHg=0.133 kPa] compared to baseline (both P<0.05). No moderate or severe mitral regurgitation or paravalvular leakage was observed. The proportion of patients with moderate-to-severe pulmonary hypertension decreased from 65.4% preoperatively to 13.0% at 1 year (P<0.05). CONCLUSIONS ViV-TMVR with the SAPIEN 3 valve for mitral biopro-sthetic valve failure is associated with high procedural success, significantly improved valve hemodynamics of the mitral value, alleviation of pulmonary hypertension, enhanced quality of life, and a low rate of complications at 1 year after the operation.
Humans ; Female ; Male ; Retrospective Studies ; Aged ; Bioprosthesis ; Heart Valve Prosthesis ; Mitral Valve/surgery* ; Heart Valve Prosthesis Implantation/methods* ; Middle Aged ; Prosthesis Failure ; Treatment Outcome ; Mitral Valve Insufficiency/surgery*

Critically ill patients often experience significant skeletal muscle wasting due to prolonged bed rest, metabolic disorders, inflammatory responses and malnutrition, which affects the patient's mobility and may also lead to increased mortality. Timely and accurate assessment of muscle status is important for optimizing treatment strategies and improving patient prognosis. There are various limitations in the current methods of assessing muscle mass, and muscle ultrasound, as a noninvasive, convenient, low-cost and suitable technique for bedside monitoring, has received increasing attention for its application in muscle assessment of critically ill patients. However, there are still a number of challenges in its practical application, such as the lack of uniform standards for the measurement method, the high dependence on the operation, and the reproducibility of the data that needs to be optimized, and so on. The aim of this article is to systematize the research progress of muscle ultrasound in muscle assessment of critically ill patients, and to discuss the advantages and limitations of its clinical application, in order to provide a scientific basis for future research and clinical practice.
Humans ; Critical Illness ; Ultrasonography ; Muscle, Skeletal/diagnostic imaging*

Objective To explore the pharmacological effects and regulatory mechanisms of Carthami Flos water extract and its main constituent,hydroxysafflower yellow A(HSYA),on primary dysmenorrhea rats with cold coagulation and blood stasis.Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank,model,HSYA(0.01 g/kg),ibuprofen(0.04 g/kg),and low(0.06 g/kg),medium(0.20 g/kg),and high(0.40 g/kg)Carthami Flos water extract dose groups using the random number table method,with six rats per group.A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin.Continuous gavage was administered for 6 days from the seventh day of modeling.After the intervention,the writhing reaction test was conducted.The rats,uteri,and ovaries were weighed to calculate the organ index.An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)contents in the uterus,thromboxane B2(TXB2)and 6-keto-prostaglondin F1α(6-keto-PGF1α)in plasma,and estradiol(E2)in the serum.Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue.Immunohistochemistry was used to determine cyclooxygenase-2(COX-2)expression in uterine tissue,whereas immunofluorescence was used to measure follicle-stimulating hormone receptor(FSH-R)expression in ovarian tissue.Western blotting was used to detect gonadotropin-releasing hormone receptor(GnRH-R)and FSH-R expression in uterine tissue.Results Compared with the blank group,the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2α in the uterus.TXB2 in the plasma and E2 in the serum were also evaluated.Additionally,6-keto-PGF1α decreased,and COX-2,GnRH-R,and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased(P＜0.05).The morphology of the uterine tissue was disordered.Compared with the model group,the low Carthami Flos water extract dose group showed a decrease in uterine index(P＜0.05).In the medium and high Carthami Flos water extract dose groups,the writhing response decreased,as did the uterine and ovarian indicesand PGE2 and TXB2 contents.The 6-keto-PGF1α content increased,whereas the GnRH-R protein expression in the uterus decreased(P＜0.05).The high Carthami Flos water extract dose group also showed a decrease in PGF2α and FSH-R protein expression in the uterus(P＜0.05).In the HSYA group,the writhing response decreased,the uterine and ovarian indices decreased,the PGE2,PGF2α,and TXB2 contents decreased,and GnRH-R and FSH-R protein expression decreased in the uterus(P＜0.05).The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced,and the uterine morphology was improved.COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced(P＜0.05).Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis.Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis.

Objective To explore the pharmacological effects and regulatory mechanisms of Carthami Flos water extract and its main constituent,hydroxysafflower yellow A(HSYA),on primary dysmenorrhea rats with cold coagulation and blood stasis.Methods Forty-two female specific pathogen-free grade rats aged 6-8 weeks were divided into blank,model,HSYA(0.01 g/kg),ibuprofen(0.04 g/kg),and low(0.06 g/kg),medium(0.20 g/kg),and high(0.40 g/kg)Carthami Flos water extract dose groups using the random number table method,with six rats per group.A rat model was established using ice water bath stimulation combined with estradiol benzoate and oxytocin.Continuous gavage was administered for 6 days from the seventh day of modeling.After the intervention,the writhing reaction test was conducted.The rats,uteri,and ovaries were weighed to calculate the organ index.An enzyme-linked immunosorbent assay and radioimmunoassay were used to detect the prostaglandin E2(PGE2)and prostaglandin F2α(PGF2α)contents in the uterus,thromboxane B2(TXB2)and 6-keto-prostaglondin F1α(6-keto-PGF1α)in plasma,and estradiol(E2)in the serum.Hematoxylin and eosin staining were used to detect the pathological changes in uterine tissue.Immunohistochemistry was used to determine cyclooxygenase-2(COX-2)expression in uterine tissue,whereas immunofluorescence was used to measure follicle-stimulating hormone receptor(FSH-R)expression in ovarian tissue.Western blotting was used to detect gonadotropin-releasing hormone receptor(GnRH-R)and FSH-R expression in uterine tissue.Results Compared with the blank group,the rats in the model group exhibited an increase in uterine and ovarian indices and increased PGE2 and PGF2α in the uterus.TXB2 in the plasma and E2 in the serum were also evaluated.Additionally,6-keto-PGF1α decreased,and COX-2,GnRH-R,and FSH-R expression in the uterus and FSH-R expression in the ovaries also increased(P＜0.05).The morphology of the uterine tissue was disordered.Compared with the model group,the low Carthami Flos water extract dose group showed a decrease in uterine index(P＜0.05).In the medium and high Carthami Flos water extract dose groups,the writhing response decreased,as did the uterine and ovarian indicesand PGE2 and TXB2 contents.The 6-keto-PGF1α content increased,whereas the GnRH-R protein expression in the uterus decreased(P＜0.05).The high Carthami Flos water extract dose group also showed a decrease in PGF2α and FSH-R protein expression in the uterus(P＜0.05).In the HSYA group,the writhing response decreased,the uterine and ovarian indices decreased,the PGE2,PGF2α,and TXB2 contents decreased,and GnRH-R and FSH-R protein expression decreased in the uterus(P＜0.05).The serum E2 levels of the groups that received Carthami Flos water extract at various doses and those of the HSYA group were reduced,and the uterine morphology was improved.COX-2 expression in the uterus and FSH-R protein expression in the ovaries were also reduced(P＜0.05).Conclusion Carthami Flos water extract and HSYA can improve the pathological state of primary dysmenorrhea rats with cold coagulation and blood stasis.Its mechanism may be related to regulating the hypothalamic-pituitary-ovary axis.