ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

ObjectiveTo explore the effects of different dosage forms of Kaixinsan （KXS） on the morphology and function of mitochondria in rat models of Alzheimer's disease （AD） and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group， model group， treatment groups receiving KXS decoction， powders， and granules （3.08 g·kg^-1）， as well as donepezil group （0.51×10^-3 g·kg^-1）， with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin （STZ）. After 30 days of administration， behavioral assessments were conducted， and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay （ELISA）. Changes in mitochondrial membrane potential were measured via JC-1 staining， and superoxide dismutase （SOD） activity and reactive oxygen species （ROS） levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， and silent information regulator 3 （SIRT3） was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and Western blot was used to examine the protein expression levels of optic atrophy protein1 （OPA1）， mitochondrial fission protein 1 （FIS1）， AMPK， p-AMPK， PGC-1α， and SIRT3. ResultsCompared with the sham group， rats in the model group had significantly lower recognition index， spontaneous alternation rate， escape latency， number of platform crossings， time spent in the target quadrant， and percentage of distance traveled in the target quadrant distance （P<0.05， P<0.01）. Significant mitochondrial damage was observed in the hippocampal tissue， with a marked decrease in mitochondrial respiratory chain complex content （P<0.01） and reduced mitochondrial membrane potential （P<0.05）. Additionally， the SOD activity was reduced， while ROS levels were elevated （P<0.01）. The mRNA expression of PGC-1α and SIRT3 was significantly downregulated （P<0.01）， along with decreased protein expression levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， whereas FIS1 protein expression was significantly upregulated （P<0.05， P<0.01）. Compared with the model group， rats in KXS-treated groups （various dosage forms） showed significant improvement in behavioral indexes （P<0.05， P<0.01）， reduced hippocampal mitochondrial damage， and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased （P<0.05， P<0.01）， and mitochondrial membrane potentials were elevated （P<0.05）. SOD activity was elevated， and ROS levels were significantly reduced （P<0.05， P<0.01）. Furthermore， the mRNA expression of PGC-1α and SIRT3 was upregulated， with increased protein levels of OPA1， p-AMPK/AMPK， PGC-1α， and SIRT3， while FIS1 protein expression levels were significantly reduced （P<0.05， P<0.01）. Across the KXS-treated groups， the granule group showed a higher spontaneous alternation rate than the decoction and powder groups （P<0.05）. ConclusionKXS decoction， powders， and granules can improve the learning and memory ability of rats， with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway， improvement of the mitochondrial function， and subsequent amelioration of the brain energy metabolism disorders.

Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective To analyze the current status,hot spots and trends of Chinese and English researches in the field of aspiration after dysphasia in the past twenty years. Methods The articles about aspiration after dysphasia were retrieved from CNKI and Web of Science(WOS)core collec-tion database,from January,2003 to June,2023,and were analyzed with CiteSpace 6.1.R6. Results A total of 3 231 articles were included.The annual articles were published more and more year by year.The most English literatures came from the United States.Hot spots mainly focused on the assessment of dysphasia,prevention of complication,nutrition and rehabilitation therapy.It would concentrate on the application of the volume-viscosity swallow test and assessment scales,rehabilitation,penetration aspiration,outcome and effect validation,quality of life,feeding and nutrition condition,and evidence-based nursing,etc.,in the future. Conclusion The researches in the field of aspiration after dysphasia have been increasing in recent years,and the themes and contents of researches have been deepening.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Objective:To analyze the spatial-temporal distribution of etiologically positive pulmonary tuberculosis (PTB) at the county (city, district) unit in Jiangsu Province from 2011 to 2021 to provide evidence for the implementation and adjustment of prevention and control strategies of PTB in Jiangsu Province.Methods:The registration data of etiologically positive PTB patients in Jiangsu Province from 2011 to 2021 were collected from the Tuberculosis Management Information System in the China Information System of Disease Control and Prevention. Data on the permanent population were from the statistical yearbook of each county (city, district) in Jiangsu Province. Geoda 1.18.0 software was used to analyze the global and local spatial autocorrelation and explore the spatial clustering. SaTScan 10.1 software was used to analyze the spatial-temporal clusters, and ArcGIS 10.7 software was used to visualize the spatial-temporal clusters.Results:A total of 128 240 etiological positive PTB cases were registered in Jiangsu Province from 2011 to 2021, with an average annual registration rate of 13.99/100 000. The registration rate showed an overall upward trend (trend χ2=63.49, P<0.001) after 2017, and the etiologically positive rate showed an overall upward trend (trend χ2=3 710.86, P<0.001). The annual Moran's I values ranged from 0.107 to 0.343, which showed a spatial clustering distribution. The results of local spatial autocorrelation analysis showed that there were "high-high" clustering areas in Jiangsu Province each year, showing a dynamic distribution, and most of the areas were distributed in the central and southern regions of Jiangsu Province, with the largest number (7) in 2015 and the smallest number (1) in 2011. A total of 4 spatial-temporal clustering areas were explored by spatial-temporal scanning analysis (all P<0.001), among which the first-level clustering area covered 3 counties (cities, districts), namely Changshu, Taicang, and Xiangcheng District of Suzhou, and the clustering time was from 2011 to 2015. The secondary clustering areas covered 24 counties (cities, districts), mainly covering Jiangsu's central and northern regions, such as Huai'an, Suqian, and Yancheng. The third-level clustering areas covered 26 counties (cities, districts); the fourth-level clustering area was the Gaochun District of Nanjing, with the clustering period from 2017 to 2021. Conclusions:From 2011 to 2021, the etiologically positive PTB registration rate at the county (city, district) level in Jiangsu Province had obvious spatial-temporal clustering characteristics. The clustering areas included the northern areas with relatively backward economies and the southern areas with better economic development. Multiple measures should be taken to prevent and control PTB according to the specific situation in different regions.

Objective:To observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR).Methods:A cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. Results:A total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups ( H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio ( OR)=1.440, 95% confidence interval ( CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [ OR=1.990, 95% CI 1.440-2.749, P<0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95% CI 0.706-0.796, P<0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. Conclusions:The NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.

[Objective]To explore the degranulation effect and mechanism of Saposhnikovia divaricata(SD)extract on rat basophilic leukemia cell line RBL-2H3 cell.[Methods]Methylthialazole tetrazolium(MTT)test was used to select the concentrations in the subsequent experiments based on impact of 5,25,50,100,200,400 μg·mL-1 SD extract on the activity of RBL-2H3 cells.Immunoglobulin E(IgE)induction was used to establish RBL-2H3 cell degranulation model.Blank control group,model group,low dose SD extract group(5 μg·mL-1),medium dose SD extract group(25 μg·mL-1),high dose SD extract group(50 μg·mL-1)and dexamethasone(DXMS)group(100 μg·mL-1)were set up,with intervention for 30 minutes.MTT test was used to detect the effect of low,medium,high-dose SD extract on activity of RBL-2H3 cell degranulation model.Toluidine blue staining was used to observe the morphology of degranulation cells and calculate degranulation rates.Immunofluorescence staining was used to detect expression of F-actin.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of β-aminohexosidase,histamine,interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ).Western blot was used to detect the expressions of phosphatidylinositide-3 kinase(PI3K),phosphorylation-PI3K(p-PI3K),protein kinase B(AKT),phosphorylation-AKT(p-AKT),p38 mitogen activated protein kinase(p38MAPK),phosphorylation-p38MAPK(p-p38MAPK),nuclear factors-κB(NF-κB),phosphorylation-NF-κB(p-NF-κB),extracellular regulated kinases(ERK)and phosphorylation-ERK(p-ERK)protein.[Results]The low,medium,high doses of SD extract(5,25,50 μg·mL-1)had no significant effects on the activity of RBL-2H3 cells(P＞0.05).Compared with blank control group,the number of toluidine blue stained cells of model group was decreased,cells shape rounded,degranulation rate was increased,expression of F-actin was decreased,the levels of β-aminohexosidase,histamine,IL-4,IL-6,TNF-α were increased,IFN-γ level was decreased,the expressions of p-PI3K/PI3K,p-AKT/AKT,p-p38MAPK/p38MAPK,p-NF-κB/NF-κB and p-ERK/ERK were increased(P＜0.01).Compared with model group,the F-actin expression of low,medium,high doses of SD extract groups and DXMS group was increased,levels of β-aminohexosidase,histamine,IL-4,IL-6 and TNF-α were decreased,IFN-γ level was increased(P＜0.01),the expressions of p-PI3K/PI3K,p-AKT/AKT,p-p38MAPK/p38MAPK,p-NF-κB/NF-κB and p-ERK/ERK were decreased(P＜0.05,P＜0.01);the number of toluidine blue stained cells in medium,high dose SD extract groups and DXMS group was increased with spindle cell shape,degranulation rate was decreased(P＜0.01).Compared with low dose SD extract group,degranulation rate of high dose SD extract group and DXMS group was decreased(P＜0.01),F-actin expression was increased(P＜0.05),p-p38MAPK/p38MAPK expressions were decreased(P＜0.01).[Conclusion]SD extract inhibited degranulation of IgE sensitized RBL-2H3 cell and decreased the levels of inflammatory mediators,its mechanism may be related to the inhibition the phosphorylation expression of PI3K/AKT,p38MAPK/NF-KB and ERK.

Objective To investigate the changes of sex hormone levels in polycystic ovary syndrome(PCOS)in infertile population after the assisted reproductive technology treatment,and to provide an evidence for the choice of the treatment.Methods The medical data of patients admitted to the First Affiliated Hospital of Kunming Medical University from January 2016 to June 2021 were collected and divided into PCOS group(103)and non-PCOS group(589)according to whether they were diagnosed with PCOS,and the sex hormone changes of the two groups were compared.Results The patients in PCOS group were younger and had the higher BMI,more sinus follicles,higher AMH value,and lower total Gn usage.The number of LH/FSH>2 in PCOS group was higher than that in non-PCOS group(P<0.05).After the treatment,LH in both groups decreased,FSH,E2 and(P<0.05)increased;The difference of LH and E2 before and after the treatment in PCOS group was greater than that in non-PCOS group<0.05).Conclusion Compared with non-PCOS infertile patients,the changes of sex hormone indexes in PCOS infertile patients before and after the treatment were more obvious.In order to obtain the better clinical effect in patients with polycystic ovaries,it is recommended to pay attention to the changes of related sex hormone levels in the course of subsequent treatment,and choose a reasonable treatment plan.