ObjectiveTo investigate the effect of 1，25（OH）₂D₃ on the level of peroxisome proliferator-activated receptor-γ （PPAR-γ） in the liver， the phenotype of hepatic macrophages， and liver inflammation in a rat model of nonalcoholic steatohepatitis （NASH）， as well as the mechanism of 1，25（OH）₂D₃ improving liver inflammation. MethodsAfter 1 week of adaptive feeding， 24 specific pathogen-free Wistar rats were randomly divided into normal group ［choline-supplemented L-amino acid-defined （CSAA） diet］， normal+1，25（OH）₂D₃ group ［CSAA diet+1，25（OH）₂D₃］， model group ［choline-deficient L-amino acid-defined diet （CDAA） diet］， and model+1，25（OH）₂D₃ group ［CDAA diet+1，25（OH）₂D₃］， with 6 rats in each group. The dose of 1，25（OH）₂D₃ was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） were measured， liver histopathology was observed， and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages， and ELISA was used to measure the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， and interleukin-10 （IL-10） in liver tissue， and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups， and the least significant difference t-test was used for further comparison； the Pearson method was used for correlation analysis. ResultsCompared with the normal group， the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT （P=0.019 and P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P<0.001）， as well as a significant increase in the level of TNF-α （P<0.001） and a significant reduction in the level of IL-4 in liver tissue （P=0.025）. The 1，25（OH）₂D₃ group had significant reductions in the serum levels of ALT （P<0.001）， the SAF score of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， and the ratio of M1 and M2 hepatic macrophages （P=0.001）， the level of IL-1β （P<0.001） and a significant increase in the level of M2 hepatic macrophages （P=0.017）， the level of IL-10 （P=0.039）， the level of IL-4 （P<0.001）， the level of PPAR-γ （P=0.016）. There were significant interactions between CDAA diet-induced NASH model and 1，25（OH）₂D₃ in serum the levels of AST and ALT （P=0.007 and P=0.008）， the SAF scores of liver histopathology （P<0.001）， the level of M1 hepatic macrophages （P<0.001）， the level of M2 hepatic macrophages （P=0.008）， the ratio of M1 and M2 of hepatic macrophages （P=0.005）， the level of TNF-α （P<0.001）， the level of IL-10 （P=0.038）， the level of IL-4 （P<0.001） and the level of PPAR-γ （P=0.009）. The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages （r=-0.415， P=0.044） and was positively correlated with M2 hepatic macrophages （r=0.435， P=0.033）， IL-10 （r=0.433， P=0.035）， and IL-4 （r=0.532， P=0.007）. ConclusionThis study shows that 1，25（OH）₂D₃ improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

OBJECTIVE: To observe the efficacy of "Biaoben acupoint compatibility" moxibustion for abdominal obesity and its effect on blood lipid, lipid accumulation product (LAP) and cardiometabolic index (CMI). METHODS: A total of 150 patients with abdominal obesity were randomly divided into an observation group (75 cases, 5 cases dropped out) and a control group (75 cases, 6 cases dropped out). The control group received lifestyle guidance. The observation group received "Biaoben acupoint compatibility" moxibustion at Zhongwan (CV12), Guanyuan (CV4) and bilateral Tianshu (ST25), Zusanli (ST36) on the basis of the control group, 20 min each time, once every other day, 3 times a week for 8 weeks. Before and after treatment, the waist circumference, hip circumference, weight, body mass index (BMI) were observed, the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured, and the LAP and CMI were calculated in the two groups. RESULTS: After treatment, the waist circumference, weight and BMI were decreased compared with those before treatment in both groups (P<0.05), the changes of the above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the hip circumference, TC level, TG level, LAP and CMI in the observation group were decreased compared with those before treatment (P<0.05), the HDL-C level was increased compared with that before treatment (P<0.05)；the changes of the TC level, TG level, LAP, CMI and HDL-C level in the observation group were larger than those in the control group (P<0.05). CONCLUSION "Biaoben acupoint compatibility" moxibustion can reduce the degree of obesity in patients with abdominal obesity, and improve blood lipid and reduce lipid accumulation.
Humans ; Acupuncture Points ; Moxibustion ; Male ; Female ; Middle Aged ; Obesity, Abdominal/blood* ; Adult ; Lipids/blood* ; Lipid Metabolism ; Triglycerides/blood* ; Young Adult ; Treatment Outcome ; Aged

OBJECTIVE: To observe the efficacy and safety of moxibustion in treating patients with central obesity of phlegm-dampness constitution. METHODS: A total of 66 patients with central obesity of phlegm-dampness constitution were randomly assigned to a moxibustion group (n=33, 3 cases dropped out) and a sham moxibustion group (n=33, 4 cases dropped out). The moxibustion group received mild moxibustion combined with lifestyle intervention; the moxibustion was applied at Shenque (CV8) and bilateral Zusanli (ST36), 30 min per session, maintaining a local skin temperature of (43±1) ℃. The sham moxibustion group received simulated moxibustion combined with lifestyle intervention; the simulated moxibustion was applied at the same acupoints, with the same session length, but with a maintained skin temperature of (37±1) ℃. Both groups were treated once every other day, three times per week for 8 consecutive weeks. Obesity-related physical indicators (waist circumference, hip circumference, body weight, body fat percentage, body mass index [BMI]), constitution evaluation indicators (phlegm-dampness constitution conversion score, symptom score), the impact of weight on quality of life-lite (IWQOL-Lite), the hospital anxiety and depression scale (HADS), and the incidence of adverse events were measured before and after treatment, and after 4 weeks of follow-up. RESULTS: Compared with before treatment, both groups showed significant reductions in waist circumference, hip circumference, body weight, body fat percentage, BMI, phlegm-dampness constitution conversion score and symptom score, IWQOL-Lite, and both anxiety and depression subscale scores of HADS after treatment and at follow-up (P<0.001). These improvements were significantly greater in the moxibustion group than those in the sham moxibustion group (P<0.001, P<0.01, P<0.05). One patient in the moxibustion group experienced a mild burn that resolved with routine care; the incidence of adverse reactions was 3.0% (1/33) in the moxibustion group and 0% (0/33) in the sham moxibustion group, with no statistically significant difference (P>0.05). CONCLUSION On the basis of lifestyle intervention, moxibustion effectively improves obesity-related physical indicators, enhances quality of life, alleviates anxiety and depression, and improves the phlegm-dampness constitution in patients with central obesity. These benefits persist for at least 4 weeks after treatment.
Humans ; Moxibustion ; Male ; Female ; Middle Aged ; Adult ; Obesity, Abdominal/psychology* ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life ; Young Adult ; Body Mass Index

Objective To investigate the relationship between the expression of platelet autophagy related factors and peritoneal metastasis of gastric cancer.Methods The data of 360 patients with gastric cancer who underwent surgery in Hunan Provincial People's Hospital from January 2021 to May 2023 were reviewed.Patients were divided into non-peritoneal metastasis group(n=322)and peritoneal metastasis group(n=38)according to whether peritoneal metastasis occurred or not.The following information was collected:patient's personal information(i.e.age,sex,body mass index)and tumor characteristics(i.e.location,size,pathological type,histopathological differentiation,lymphatic infiltration).Platelets were collected from all subjects,and the levels of autophagy-associated protein 7(ATG7),benzalkonium chloride 1(BECN1),microtubule-associated protein 1 light chain 3(LC3)and sequestosome 1(p62)were measured by enzyme-linked immunosorbent assay(ELISA).Results Among the 360 patients included,peritoneal metastasis was detected in 38 cases.Compared with the non-peritoneal metastasis group,the peritoneal metastasis group exhibited decreased BMI(P<0.05),while the tumor size,non-ulcerative tumor,number of lymph node metastasis,infiltration depth,number of cases of lymphatic invasion,platelet count,platelet LC3-Ⅱ level,platelet ATG7 level and CEA level were increased(P<0.05).Multivariate logistic regression analysis showed that BMI(OR=1.094),lymphatic invasion(OR=2.658),and LC3-Ⅱ(OR=3.793)and ATG7(OR=2.010)were independent influencing factors for peritoneal metastasis in patients with gastric cancer(P<0.05).LC3-Ⅱ>2.59ng/ml had the highest ability to predict peritoneal metastasis in patients with gastric cancer(AUC=0.932),followed by ATG7(AUC=0.916).Conclusions Elevated levels of platelet LC3-Ⅱ and ATG7 are independently related to peritoneal metastasis in patients with gastric cancer,and can be used to predict the occurrence of peritoneal metastasis,which is helpful to guide individualized treatment.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

Objective:To summarize the characteristics of the participants (P), interventions (I), control measures (C), outcomes (O) and study design (S) of the clinical study of chronic back pain (CBP) in recent years; To further systematically organize the outcomes of the clinical study of CBP and their corresponding measurement tools.Methods:Clinical studies of CBP were retrieved from various databases including CNKI, Wanfang Database, VIP, SinoMed, Cochrane Library, Pubmed, Embase, Web of Science, etc. The search period was from January 1, 2015 to December 31, 2019. The retrieved literature was extracted and analyzed.The retrieved literatures will be extracted and analyzed. The retrieved literature was subjected to data extraction and analysis, and the quality of outcome indicators was evaluated according to 6 items. The Newcastle-Ottawa Scale ( NOS ) was used to evaluate the quality of cohort studies and case-control studies. Analyze the relationship between outcome indicators and interventions.Results:A total of 3 028 articles were finally included after examination and screening. The top 7 diagnoses of CBP were low back pain, lumbar disc protrusion, lumbar vertebral stenosis, lumbar vertebral slip, lumbar disc degression, non-specific chronic low back pain and post-operative pain syndrome. The top 7 intervention measures in clinical studies of CBP were surgery, acupuncture, physiotherapy, Tuina, exercise therapy, Western medicine painkillers and oral Chinese patent medicines. A total of 47 outcomes and 348 outcome measurement tools were reported in the literature included.Conclusion:In the clinical study of CBP in the recent years, there are problems such as incomplete and low quality of reporting, a wide variety of outcome measurement tools and lack of uniform reporting standards. The characteristics of patients determine the common characteristics of outcomes selection and it is also necessary to consider the specific outcomes related to interventions.