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 investigate the molecular mechanism by which Feiyanning formula（FYN） regulated exosomal miR-328 to suppress the invasion and metastasis of lung cancer. MethodsIn vitro models using low-metastatic 95C and high-metastatic 95D lung cancer cell lines， along with isolated exosomes， were established. Initially， 95C and 95D cells were cultured， and exosomes were isolated from their supernatants. The exosomes were identified using transmission electron microscopy （TEM）， nanoparticle tracking analysis （NTA）， and Western blot. Exosome uptake assays confirmed that both 95C and 95D cells could internalize exosomes derived from lung cancer patients' plasma. Cell counting kit-8 （CCK-8） assays were performed to assess the inhibitory effects of FYN （0， 0.1， 0.2， 0.4， 0.8， 1.6， 3.2， 6.4 g·L^-1） on 95C and 95D cell proliferation. Subsequent experiments were divided into three groups of control， low-dose FYN （1 g·L^-1）， and high-dose FYN （2 g·L^-1） groups. Wound-healing and Transwell assays were used to evaluate the inhibitory effects of FYN on the migration and invasion of 95C and 95D cells. Western blot was employed to detect the protein expression levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3）， cellular oncogene Fos （c-Fos）， and nuclear factor of activated T cells 1 （NFATc1）. The mRNA expression of miR-328 was measured by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsLung cancer plasma-derived exosomes （EXO） enhanced the migration， invasion， and miR-328 expression levels in 95C and 95D cells （P<0.05， P<0.01）. FYN inhibited the proliferation， invasion， and metastasis of 95C and 95D cells in a dose-dependent manner （P<0.01）， with more pronounced effects on 95C cells. Additionally， FYN downregulated exosomal miR-328 expression and suppressed the protein levels of JAK2， STAT3， and its downstream target genes c-Fos and NFATc1 （P<0.01）. ConclusionFYN may inhibit lung cancer metastasis by downregulating exosomal miR-328 expression， potentially through the STAT3/c-Fos/NFATc1 signaling pathway. Further studies are warranted to elucidate its detailed mechanisms and facilitate clinical application， providing insights into traditional Chinese medicine-based strategies for lung cancer treatment.

Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Tumor immunotherapy has emerged as a highly esteemed and rapidly evolving field in recent years,marked by the development of numerous significant therapeutic approaches. Among these,immune checkpoint inhibitors stand out as a pivotal strategy,attracting considerable attention due to their substantial research progress. This article provides a comprehensive review of the current research advancements in ten key immune checkpoints related to anti-tumor therapy,including PD-1/PD-L1,CTLA-4,LAG-3,TIM-3,TIGIT,and VISTA. By conducting an in-depth analysis of their mechanisms of action,clinical applications,and future research directions,this review aims to offer valuable insights and guidance for optimizing strategies in tumor immunotherapy.

BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Sepsis poses a significant threat to hu-man health due to its widespread prevalence,high mortality rate,substantial treatment costs,and the absence of effective life-saving therapies.Melato-nin,a primary hormone regulating the circadian rhythm,has demonstrated potential as a promising therapeutic agent against sepsis.Its anti-inflamma-tory,antioxidant,immunomodulatory,mitochondri-al protective,and multi-organ protective effects are noteworthy.In this review,we summarize current research on the mechanisms of action and clinical efficacy of melatonin in sepsis treatment and multi-organ function preservation,aiming to offer new perspectives and support for sepsis research and therapy.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.