Objective To investigate the effect of platelet lysate on mitochondrial function of astrocytes after spinal cord injury.Methods Astrocytoma cells SVGp12 were incubated with different concentrations of H2O2 (100 μmol/L,400 μmol/L,1000 μmol/L,2000 μmol/L),and the OD value was determined by CCK-8 assay. The H2O2 concentration with a cell inhibition rate of about 50％ was selected for follow-up experiments. The cells were incubated with different concentrations of platelet lysate (the volume ratios of platelet lysate to culture medium were 1∶10,1∶40,1∶80,1∶160 and 1∶320) for 24 hours,and the OD value was determined,thereby selecting the optimal concentration of platelet lysate based on the cell survival rate. SVGp12 cells were divided into the normal group (cultured normally without special treat-ment),the model group (incubated with 1000 μmol/L of H2O2 for 3 hours),and the treatment group (incubated with 1000 μmol/L of H2O2 for 3 hours and then treated with platelet lysate at a volume ratio of 1∶80). The mitochondrial function was evaluated by mitochondrial activity staining,mitochondrial membrane potential detection,and mitochondrial permeability transition pore detection. Results After incubating cells with 1000 μmol/L of H2O2 for 3 hours,the cell inhibition rate was 48％,and the OD value decreased significantly (P<0.01),confirming the successful establishment of a model of astrocytes with spinal cord injury. After treated with different concentrations of platelet lysate,the OD values and cell survival rate of the cells were higher than those in the model group (P<0.05). The concentration of platelet lysate (volume ratio of 1∶80) with cell viability of 20％ was selected for follow-up experiments. Platelet lysate could improve the morphology of injured astrocytes. The mitochondrial activity of the treatment group was significantly higher than that of the model group,and the mitochondrial activity of the model group was significantly lower than that of the normal group,with statistically significant differences (P<0.05). The mitochondrial membrane potential in the model group was lower than that in the normal group,and the mitochondrial membrane potential in the treatment group was higher than that in the model group,with statistically significant differences (P<0.01). The mitochondrial permeability in the model group was greater than that in the normal group,and the mitochondrial permeability in the treatment group was smaller than that in the model group,with statistically significant differences (P<0.01).Conclusion Platelet lysate can improve the survival rate of astrocytes after spinal cord injury,enhance the mitochondrial activity of cells,and improve the mitochondrial membrane potential and mitochondrial permeability transition pore opening.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of platelet lysate on mitochondrial function of astrocytes after spinal cord injury.Methods Astrocytoma cells SVGp12 were incubated with different concentrations of H2O2 (100 μmol/L,400 μmol/L,1000 μmol/L,2000 μmol/L),and the OD value was determined by CCK-8 assay. The H2O2 concentration with a cell inhibition rate of about 50％ was selected for follow-up experiments. The cells were incubated with different concentrations of platelet lysate (the volume ratios of platelet lysate to culture medium were 1∶10,1∶40,1∶80,1∶160 and 1∶320) for 24 hours,and the OD value was determined,thereby selecting the optimal concentration of platelet lysate based on the cell survival rate. SVGp12 cells were divided into the normal group (cultured normally without special treat-ment),the model group (incubated with 1000 μmol/L of H2O2 for 3 hours),and the treatment group (incubated with 1000 μmol/L of H2O2 for 3 hours and then treated with platelet lysate at a volume ratio of 1∶80). The mitochondrial function was evaluated by mitochondrial activity staining,mitochondrial membrane potential detection,and mitochondrial permeability transition pore detection. Results After incubating cells with 1000 μmol/L of H2O2 for 3 hours,the cell inhibition rate was 48％,and the OD value decreased significantly (P<0.01),confirming the successful establishment of a model of astrocytes with spinal cord injury. After treated with different concentrations of platelet lysate,the OD values and cell survival rate of the cells were higher than those in the model group (P<0.05). The concentration of platelet lysate (volume ratio of 1∶80) with cell viability of 20％ was selected for follow-up experiments. Platelet lysate could improve the morphology of injured astrocytes. The mitochondrial activity of the treatment group was significantly higher than that of the model group,and the mitochondrial activity of the model group was significantly lower than that of the normal group,with statistically significant differences (P<0.05). The mitochondrial membrane potential in the model group was lower than that in the normal group,and the mitochondrial membrane potential in the treatment group was higher than that in the model group,with statistically significant differences (P<0.01). The mitochondrial permeability in the model group was greater than that in the normal group,and the mitochondrial permeability in the treatment group was smaller than that in the model group,with statistically significant differences (P<0.01).Conclusion Platelet lysate can improve the survival rate of astrocytes after spinal cord injury,enhance the mitochondrial activity of cells,and improve the mitochondrial membrane potential and mitochondrial permeability transition pore opening.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

Objective To verify the therapeutic effect of platelet lysate(PL)on spinal cord injury in rats.Methods Thirty male SD rats were randomly divided into the sham operation group,the injury group and the treatment group,with 10 rats in each group.Rats in the sham operation group did not smash the spinal cord after exposure;rats in the injury group were established the rat spinal cord injury model by smashing the spinal cord with a 20 g of self-made smashing machine weights from a height of 5 cm for 5 seconds after exposure;rats in the treatment group were given intraperitoneal injection of 2 mL of PL once a day for 19 days after established the spinal cord injury model.The hind limb function was evaluated by Basso Beattie Bresnahan(BBB)score and slope experiment;six rats were randomly selected from each group,and the spinal cords of the rats were taken on the 7th day after surgery for HE staining and electron microscopy scanning to observe their pathological changes.Results There were statistically significant differences in BBB scores on the 3rd,7th and 14th days after surgery among the three groups(P<0.05),and the BBB scores of the treatment group were higher than those of the injury group(P<0.05).There were statistically significant differences in the results of slope experiment on the 7th and 14th days after surgery between the treatment group and the injury group(P<0.01).HE staining showed that the neuronal degeneration and necrosis decreased,the cell swelling improved and the microglial phagocytosis decreased in the treatment group compared with those in the injury group.The results of electron microscopy showed that the astrocyte cytoplasmic swelling and local cell membrane damage were alleviated,and the mitochondrial swelling and degeneration in the treatment group were relieved compared with those in the injury group.Conclusion PL can improve the hind limb function and reduce the pathological changes after spinal cord injury in rats,which has therapeutic effect on spinal cord injury in rats.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*