Post-stroke cognitive impairment(PSCI)is a prevalent functional impairments following stroke that seriously affects patients'quality of life and daily activities.Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases.Intestinal microflora profoundly impacts on human physiological health,contributing to the stability of nervous,metabolic and immune systems through regulation of the gut-brain axis.An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI,and regulation of microbiome-gut-brain could be potential target to treatment of PSCI.This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Objective:To compare the efficacy and clinical value of high-throughput sequencing(HTS)and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia(CML).Methods:A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain,and the relevant clinical data were collected for comparative analysis.Results:The proportion of total mutations and ≥ 2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing(P=0.01;P=0.046).≥ 2 mutations were detected in 22 cases,of which 5 cases(22.7％)had compound mutations.High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing.In 198 samples,25(12.6％)were low level mutations,33(16.7％)were high level mutations and 10(5.1％)were mixed high and low level mutations.In the analysis of related clinical factors,the total mutation rate and the low level mutation rate in the optimal period,failure period and warning period were gradually increased(total mutation rate,P=0.016;low level mutation rate,P=0.005).The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased(P=0.009).The mutation rate of patients who received first-and second-line treatment was significantly lower than that of patients who received third-or higher-line treatment(P=0.006).Analysis based on variant allele frequency(VAF)of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells.Conclusion:High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection,which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.
Rats ; Animals ; Mitophagy/physiology* ; Rats, Sprague-Dawley ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology* ; Gyrus Cinguli ; Neuralgia ; Ubiquitin-Protein Ligases/metabolism* ; Protein Kinases ; Membrane Proteins/metabolism* ; Mitochondrial Proteins/metabolism*

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.
Adult ; Female ; Humans ; Male ; Alcohol Drinking ; Diseases in Twins/genetics* ; Hypertension/genetics* ; Twins, Dizygotic/genetics* ; Twins, Monozygotic/genetics*

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.
Adult ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China/epidemiology* ; Diseases in Twins/genetics* ; Hyperlipidemias/genetics* ; Metabolic Diseases ; Twins, Dizygotic ; Twins, Monozygotic/genetics*

Objective: To understand HIV self-testing and related factors in men who have sex with men (MSM) in Shijiazhuang. Methods: From August to September 2020, convenient sampling was used to recruit MSM in Shijiazhuang. Online questionnaires were used to collect information about their demographic characteristics, sexual behaviors and HIV self-testing. logistic regression model was used to analyze the related factors associated with HIV self-testing. Results: In the 304 MSM respondents, 52.3% (159/304) had HIV self-testing in the past 6 months, and 95.0% (151/159) used fingertip blood HIV detection reagent. Self-purchase was the main way to obtain HIV testing reagents (45.9%, 73/159), followed by supply from MSM social organization (44.7%, 71/159). The reasons for having HIV self-testing were non-specific testing time (67.9%, 108/159) and privacy protection (62.9%,100/159), the reasons for having no HIV self-testing included inability of using (32.4%, 47/145), being unaware of HIV self-testing reagent (24.1%, 35/145), and worry about inaccurate self-testing results (19.3%, 28/145). Multivariate logistic regression analysis showed that being 18-29 years old (aOR=2.68, 95%CI: 1.20-5.94), obtaining free HIV self-testing kits in recent 6 months (aOR=8.61, 95%CI: 4.09-18.11) and making friends through Internet and social software (aOR=2.68, 95%CI: 1.48-4.88) were positive factors for having HIV self-testing. Conclusion: HIV self-testing is a more flexible and convenient way to detect HIV in MSM, and the promotion of HIV self-testing in MSM should be strengthened to further increase the HIV detection rate in this population.
Male ; Humans ; Adolescent ; Young Adult ; Adult ; Homosexuality, Male ; Self-Testing ; Sexual and Gender Minorities ; HIV Testing ; Sexual Behavior

Objective: To investigate the associations between the numbers of healthy lifestyles and overweight/obesity and abdominal obesity in adult twins in Shanghai. Methods: Based on the Shanghai Twin Registry System Phase Ⅱ survey data in 2017-2018, a case-control study was conducted to analyze the association between healthy lifestyles and obesity and further adjusted for confounders by a co-twin control study. Results: A total of 7 864 adult twins (3 932 pairs) were included. In the co-twin case-control analysis for monozygotic twins, compared with participants with 0 to 2 healthy lifestyles, those with 3 and 4 to 5 healthy lifestyles had a 49% (OR=0.51, 95%CI: 0.28-0.93) and 70% (OR=0.30, 95%CI: 0.13-0.69) lower risk of overweight/obesity, respectively, and a 17% (OR=0.83, 95%CI: 0.44-1.57) and 66% (OR=0.34, 95%CI: 0.14-0.80) lower risk of abdominal obesity, respectively. For each additional healthy lifestyle, the risk of developing overweight/obesity was reduced by 41% (OR=0.59, 95%CI: 0.42-0.85), and the risk of developing abdominal obesity was reduced by 37% (OR=0.63, 95%CI: 0.44-0.90). Conclusion: An increasing number of healthy lifestyles was associated with a marked decreased risk for both overweight/obesity and abdominal obesity.
Adult ; Humans ; Case-Control Studies ; China/epidemiology* ; Healthy Lifestyle ; Obesity/epidemiology* ; Obesity, Abdominal/epidemiology* ; Overweight/epidemiology* ; Twins, Monozygotic

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Objective:To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis.Methods:A prospective study was conducted. The patients aged ≥18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL·kg -1·h -1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. Results:Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHEⅡ score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHEⅡ score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×10 9/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (μg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (μg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (μg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). Conclusion:CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.