BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

ObjectiveTo explore the inhibitory effect and related molecular mechanisms of Saponin of Schizocapsa plantaginea HanceⅠ （SSPHⅠ） on human nasopharyngeal carcinoma HONE-1 cells. MethodsThe effect of SSPHⅠ on HONE-1 cell viability was detected using the CCK-8 assay. Its inhibitory effect on cell proliferation was evaluated through a colony formation assay. Changes in cell invasion ability were analyzed using the Transwell assay. Intracellular reactive oxygen species （ROS） levels were measured using the DHE fluorescent probe. The extent of intracellular content release was reflected by the LDH release assay. The rate of cell pyroptosis was detected using the Annexin-V/PI double staining method. Changes in the expression of proteins related to the classical pyroptosis pathway were examined by Western Blot. ResultsCCK-8 assay showed that treatment with SSPHⅠ for 24 hours reduced HONE-1 cell viability in a concentration-dependent manner， with an IC50 value of 3.383 μmol/L. In the colony formation assay， the number of HONE-1 cell colonies gradually decreased with increasing concentrations of SSPHⅠ （P<0.01）. The Transwell assay revealed that the number of cells migrating through the chamber was reduced following SSPHⅠ treatment （P<0.01）. DHE fluorescence probe detection indicated that intracellular ROS fluorescence intensity increased after SSPHⅠ treatment （P<0.001）. The LDH release assay showed that LDH activity in the cell supernatant increased with higher concentrations of SSPHⅠ （P<0.001）. Annexin-V/PI double staining demonstrated that the proportion of Annexin-V/PI-positive cells increased after SSPHⅠ treatment （P<0.001）. Western blot analysis showed that， compared with the control group， the protein expression levels of cleaved-Caspase-1 and GSDMD-N-terminal were upregulated in SSPHⅠ-treated cells （P<0.05）， and NLRP3 protein expression levels also increased （P<0.05）. ELISA results showed that the levels of IL-1β and IL-18 in the cells increased with higher concentrations of SSPHⅠ （P<0.05）. ConclusionSSPHⅠ can induce pyroptosis in nasopharyngeal carcinoma HONE-1 cells by regulating the ROS/NLRP3/Caspase-1 signaling axis， thereby exerting an anti-nasopharyngeal carcinoma effect. This suggests that SSPHⅠ may serve as a potential therapeutic agent for nasopharyngeal carcinoma.

OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Capsules ; Carcinoma/drug therapy*

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Prostate cancer(PCa) is a common malignant tumor among elderly men, with high incidence and mortality rates worldwide, posing a serious threat to human health. Traditional treatments face limitations, highlighting the urgent need for novel therapeutic strategies. Recent studies on the regulatory mechanisms of micro ribonucleic acid(microRNA, miRNA) in tumor development has identified miRNA as new targets for PCa diagnosis and treatment. Traditional Chinese medicine(TCM), with its multi-mechanism, multi-target, and multi-pathway regulatory properties, shows promising potential in miRNA-based PCa therapy. This review summarized recent findings on miRNA' roles in PCa and research progress of TCM intervention and found that a variety of miRNA played important regulatory roles in cell differentiation, proliferation, apoptosis, invasion, metastasis, immune microenvironment, and drug resistance, and their potential as biomarkers for PCa diagnosis, prognosis, and therapy, indicating the potential to be a biomarker for the diagnosis, prognosis evaluation, and treatment of PCa. The review concluded that the active components of TCM(terpenoids, flavonoids, alkaloids, and others) and compounds(Yishen Tonglong Decoction, Shenhu Decoction, Zhoushi Qiling Decoction, Fuzheng Yiliu Decoction, and Qilan Formula) could regulate the expression of their downstream target genes by acting on specific miRNA and affect the above biological behaviors of PCa cells, thus playing a role in the treatment of PCa. This review aims to provide a theoretical basis for miRNA as potential biomarkers and therapeutic targets for PCa and suggest new avenues for further development of targeted therapy strategies against miRNA.
Humans ; MicroRNAs/metabolism* ; Prostatic Neoplasms/metabolism* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Animals ; Gene Expression Regulation, Neoplastic/drug effects*