Objective To explore the effects of Shuanglu Tongnao Formula on neuroinflammation in ischemic stroke (IS) rats via the P2X purinoceptor 7 receptor (P2X7R)/NLR family pyrin domain-containing 3 (NLRP3) pathway. Methods The rats were divided into five groups: the IS group, control group, Shuanglu Tongnao Formula group, P2X7R inhibitor brilliant blue G (BBG) group, and Shuanglu Tongnao Formula combined with P2X7R activator adenosine triphosphate (ATP) group, with 18 rats in each group. Except for the control group, rats in all other groups were used to construct an IS model using the suture method. After successful modeling, the drug was given once a day for 2 weeks. Neurological function scores and cerebral infarction volume ratios were measured in rats. Pathological examination of the ischemic penumbra brain tissue was performed. Immunofluorescence staining was used to quantify the proportions of microglia co-expressing both inducible nitric oxide synthase (iNOS) and ionized calcium-binding adapter molecule 1 (Iba1), as well as arginase 1 (Arg1) and Iba1, in the ischemic penumbra brain tissue. ELISA was used to detect tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukin 6 (IL-6) and IL-10 in the ischemic penumbra brain tissue. Western blotting was used to measure P2X7R, NLRP3, and IL-1β proteins in the ischemic penumbra brain tissue. Results Compared with the control group, the IS group showed disordered neuronal arrangement, nuclear condensation, and obvious infiltration of inflammatory cells in the ischemic penumbra; significantly elevated neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with reduced proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. Compared with the IS group, the Zhuang medicine Shuanglu Tongnao Formula and BBG groups demonstrated alleviated brain tissue damage; reduced neurological function scores, cerebral infarction volume ratios, proportions of microglia co-expressing iNOS and Iba1, and levels of TNF-α, IL-6, and P2X7R, NLRP3, IL-1β proteins; along with increased proportions of microglia co-expressing Arg1 and Iba1 and levels of TGF-β and IL-10. ATP reversed the effects of Zhuang medicine Shuanglu Tongnao Formula on microglial polarization and neuroinflammation in IS rats. Conclusion Zhuang medicine Shuanglu Tongnao Formula may promote the transformation of microglia from M1 type to M2 type by inhibiting the P2X7R/NLRP3 pathway, thereby improving neuroinflammation in IS rats.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Male ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Ischemic Stroke/pathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Interleukin-10/metabolism* ; Brain Ischemia/drug therapy* ; Microglia/metabolism*

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

We report a case of a young female patient with fatigue, hypokalemia, and hyperglycemia. She had past-history of diabetes mellitus, and was admitted to hospital with a history of fatigue and hypokalemia for 5 years. The patient's examination indicated hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and SLC12A3 gene pathogenic mutation. The diagnosis was Gitelman syndrome. Potassium and magnesium supplements were given to improve the patient's fatigue. Serum potassium and magnesium were normal. The blood glucose reached standard after treatment with oral hypoglycemic drugs. This article incorporates literature review to sort out the diagnosis and treatment of Gitelman syndrome, in order to provide feasible reference for clinicians.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95％CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95％CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P＜0.1).Multivariate analysis showed that the risk of death in patients with onset age＞65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0％CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0％CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P＜0.001,95.0％CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.

Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.