ObjectiveTo perform metabolic associated fatty liver disease （MAFLD） screening among individuals attending community health institutions， to identify the patients at a low， moderate or high risk of advanced liver fibrosis based on fibrosis-4 index （FIB-4） and liver stiffness measurement （LSM） measured by liver transient elastography， and to implement stratified management. MethodsA cross-sectional study was conducted among 630 individuals attending Beijing Baizhifang Community Health Service Center from January to July 2024， and they were divided into MAFLD group and non-MAFLD group. According to body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<23 kg/m²） and non-lean MAFLD group （BMI≥23 kg/m²）. The above groups were compared in terms of demographic features， laboratory markers， hepatic steatosis， and LSM. Fibrosis risk stratification was performed for MAFLD patients based on FIB-4 and LSM， and a closed-loop management system involving referral to tertiary hospitals and follow-up at community health institutions was implemented. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThere were 445 individuals （70.6%） in the MAFLD group and 185 individuals （29.4%） in the non-MAFLD group. Compared with the non-MAFLD group， the MAFLD group had a significantly lower proportion of male individuals （χ²=4.299， P<0.05）， a significant reduction in the level of high-density lipoprotein cholesterol （Z=3.484， P<0.05）， and significant increases in body weight （Z=-7.366， P<0.05）， BMI （Z=-9.740， P<0.05）， waist circumference （Z=-6.397， P<0.05）， hip circumference （Z=-6.935， P<0.05）， alanine aminotransferase （ALT） （Z=-2.765， P<0.05）， fasting blood glucose （Z=-3.646， P<0.05）， triglyceride （TG） （Z=-6.569， P<0.05）， total cholesterol （Z=-2.033， P<0.05）， low-density lipoprotein cholesterol （Z=-2.935， P<0.05）， controlled attenuation parameter （CAP） （Z=-19.784， P<0.05）， and LSM （Z=-5.703， P<0.05）. Within the MAFLD group， there were 124 individuals （27.9%） in the lean MAFLD group and 321 individuals （72.1%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly lower body weight （Z=-12.414， P<0.05）， BMI （Z=-16.363， P<0.05）， waist circumference （Z=-7.733， P<0.05）， hip circumference （Z=-8.595， P<0.05）， ALT （Z=-2.835， P<0.05）， aspartate aminotransferase （Z=-1.972， P<0.05）， TG （Z=-2.407， P<0.05）， CAP （Z=-4.429， P<0.05）， degree of steatosis （χ²=16.588， P<0.05）， and LSM （Z=-3.908， P<0.05）. Based on the results of FIB-4 and LSM， 76 patients at a moderate or high risk of liver fibrosis should be referred to a higher-level hospital for further management. ConclusionThe detection rate of MAFLD reaches 70.6% among the individuals attending community health institutions， among whom 76 （17.1%） should be referred to a higher-level hospital. Establishing a liver fibrosis risk stratification and management system based on FIB-4 and LSM among MAFLD individuals in communities provides a practical pathway for chronic disease management and referral system construction in community health institutions.

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

Objective To investigate the effect of indigo on inflammatory factors and the aryl hydrocarbon receptor(AhR)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in lipopolysaccharide(LPS)-induced keratinocytes(HaCaT cells).Methods An LPS-induced HaCaT cell model was established,and experimental groups were set as follows:blank group,model group,indigo group,AhR agonist(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD)group,AhR inhibitor(CH-223191)group,and indigo+AhR inhibitor group.The Cell Counting Kit-8(CCK-8)assay was used to detect the effects of different concentrations of indigo,TCDD,and CH-223191 on HaCaT cell viability after 24 hours of intervention.Quantitative real-time PCR(qPCR)was employed to measure the mRNA expression levels of interleukin-1β(IL-1β),nuclear factor kappa B(NF-κB),tumor necrosis factor-α(TNF-α),AhR,cytochrome P450 family 1 subfamily A member 1(CYP1A1),NLRP3,Caspase-1,and apoptosis-associated speck-like protein(ASC)in each group.Western Blot analysis was used to assess changes in the cellular localization of AhR protein expression.Results(1)The IC50 of indigo intervention in HaCaT cells was 118.7 μmol·L-1.Treatment with different concentrations of CH-223191 and TCDD for 24 hours had no significant effect on HaCaT cell viability.(2)Compared with the model group,the indigo group showed decreased mRNA expression levels of IL-1β,NF-κB,NLRP3,and Caspase-1(P＜0.05 or P＜0.000 1),while the mRNA expression levels of AhR and CYP1A1 were significantly increased(P＜0.05 or P＜0.000 1).(3)Compared with the blank group,the indigo group reduced cytoplasmic AhR protein expression and increased nuclear AhR protein expression(P＜0.001 or P＜0.000 1).(4)Compared with the model group,both the indigo group and the AhR agonist group significantly increased AhR mRNA expression levels(P＜0.05),while the AhR inhibitor group decreased AhR and CYP1A1 mRNA expression levels(P＜0.05)and increased IL-1β and NLRP3 mRNA expression levels(P＜0.05).(5)Compared with the AhR inhibitor group,the indigo+AhR inhibitor group showed increased mRNA expression levels of AhR and CYP1A1(P＜0.05)and decreased mRNA expression levels of NLRP3,Caspase-1,and IL-1β(P＜0.05).Conclusion Indigo reduces inflammatory factors in LPS-induced HaCaT cells and participates in inhibiting the occurrence and development of psoriasis by activating AhR to negatively regulate the NLRP3 inflammasome.

ObjectiveTo screen for the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the physical examination population， to observe the characteristics of MAFLD patients， and to compare the differences in lifestyle between the MAFLD population and the non-MAFLD population. MethodsA cross-sectional study was conducted among 6 206 individuals who underwent physical examination in a physical examination institution in Beijing from December 2015 to December 2019， and according to the new diagnostic criteria for MAFLD， the examination population was divided into MAFLD group and non-MAFLD group. Based on body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<24 kg/m²） and non-lean MAFLD group （BMI ≥24 kg/m²）. Related data were compared between groups， including demographic indicators， education level， work pressure， physical measurement indicators， and lifestyles such as sleep， diet， and exercise. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test was used for comparison of categorical data between groups. ResultsOf all individuals in this study， 1 926 （31.1%） had MAFLD and 4 280 （68.9%） did not have MAFLD. Compared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-14.459， P<0.001）， proportion of male patients （χ²=72.004， P<0.001）， work pressure （χ²=7.744， P=0.005）， body weight （Z=-43.508， P<0.001）， BMI （Z=-47.621， P<0.001）， waist circumference （Z=-48.515， P<0.001）， hip circumference （Z=-42.121， P<0.001）， and waist-hip ratio （Z=-43.535， P<0.001）， as well as a significantly lower education level （χ²=33.583， P<0.001）. In terms of behavior， the MAFLD group had a significantly shorter sleep time （χ²=5.820， P=0.016） and a significantly faster eating speed （χ²=74.476， P<0.001）. In terms of diet， the patients in the MAFLD group consumed more high-sodium， high-sugar， and high-calorie diets （χ²=42.667， P<0.001） and low-fiber diet （χ²=4.367， P=0.008）. In terms of exercise， the MAFLD group had a significantly higher proportion of patients without exercise habits （χ²=10.278， P=0.001）. Further analysis showed that there were 202 individuals （10.5%） in the lean MAFLD group and 1 724 （89.5%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.368， P=0.001） and education level （χ²=9.647， P=0.002） and significantly lower proportion of male patients （χ²=27.664， P<0.001）， body weight （Z=-18.483， P<0.001）， BMI （Z=-23.286， P<0.001）， waist circumference （Z=-18.565， P<0.001）， and hip circumference （Z=-18.097， P<0.001）， and in terms of behavior， the non-lean MAFLD group had a significantly faster eating speed （χ²=4.549， P=0.033）. ConclusionThere is a relatively high prevalence rate of MAFLD among the physical examination population in Beijing， with a higher number of people with unhealthy lifestyles compared with the non-MAFLD population.

ObjectiveTo identify the patients with metabolic dysfunction-associated fatty liver disease （MAFLD） among the health check-up population， and to perform stratified management of patients with the low， medium， and high risk of advanced fibrosis based on noninvasive fibrosis scores. MethodsA cross-sectional study was conducted among 3 125 individuals who underwent physical examination in Beijing Physical Examination Center from December 2017 to December 2019， and they were divided into MAFLD group with 1 068 individuals and non-MAFLD group with 2 057 individuals. According to BMI， the MAFLD group was further divided into lean MAFLD group （125 individuals with BMI<24 kg/m²） and non-lean MAFLD group （943 individuals with BMI≥24 kg/m²）. Indicators including demographic data， past history， laboratory examination， and liver ultrasound were compared between groups. Fibrosis-4 （FIB-4） score， NAFLD fibrosis score （NFS）， aspartate aminotransferase-to-platelet ratio index （APRI）， and BARD score were calculated for the patients in the MAFLD group to assess the risk of advanced fibrosis. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influence of each indicator in MAFLD. ResultsCompared with the non-MAFLD group， the MAFLD group had significantly higher age （Z=-9.758， P<0.05）， proportion of male patients （χ²=137.555， P<0.05）， and levels of body weight （Z=-27.987， P<0.05）， BMI （Z=-32.714， P<0.05）， waist circumference （Z=-31.805， P<0.05）， hip circumference （Z=-26.342， P<0.05）， waist-hip ratio （Z=-28.554， P<0.05）， alanine aminotransferase （ALT） （Z=-25.820， P<0.05）， aspartate aminotransferase （AST） （Z=-16.894， P<0.05）， gamma-glutamyl transpeptidase （GGT） （Z=-25.069， P<0.05）， alkaline phosphatase （Z=-12.533， P<0.05）， triglyceride （Z=-27.559）， total cholesterol （Z=-7.833， P<0.05）， low-density lipoprotein cholesterol （LDL-C） （Z=-8.222， P<0.05）， and uric acid （UA） （Z=-20.024， P<0.05）， as well as a significantly higher proportion of patients with metabolic syndrome （MetS） （χ²=578.220， P<0.05）， significantly higher prevalence rates of hypertension （χ²=241.694， P<0.05）， type 2 diabetes （χ²=796.484， P<0.05）， and dyslipidemia （χ²=369.843， P<0.05）， and a significant reduction in high-density lipoprotein cholesterol （HDL-C） （Z=23.153， P<0.001）. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=1.45， 95% confidence interval ［CI］： 1.203‍ ‍—‍ ‍1.737）， ALT （OR=1.05， 95%CI： 1.046‍ ‍—‍ ‍1.062）， LDL-C （OR=1.23， 95%CI： 1.102‍ ‍—‍ ‍1.373）， and comorbidity with MetS （OR=5.97， 95%CI： 4.876‍ ‍—‍ ‍7.316） were independently associated with MAFLD. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly higher age （Z=3.736， P<0.05） and HDL-C （Z=2.679， P<0.05） and significant reductions in the proportion of male patients （χ²=28.970， P<0.05）， body weight （Z=-14.230， P<0.05）， BMI （Z=-18.188， P<0.05）， waist circumference （Z=-13.451， P<0.05）， hip circumference （Z=-13.317， P<0.05）， ALT （Z=-4.519， P<0.05）， AST （Z=-2.258， P<0.05）， GGT （Z=-4.592， P<0.05）， UA （Z=-4.415， P<0.05）， the proportion of patients with moderate or severe fatty liver disease or MetS （χ²=42.564， P<0.05）， and the prevalence rates of hypertension （χ²=12.057， P<0.05） and type 2 diabetes （χ²=3.174， P<0.05）. Among the patients with MAFLD， 10 patients （0.9%） had an FIB-4 score of >2.67， 4 patients （0.4%） had an NFS score of >0.676， 8 patients （0.7%） had an APRI of >1， and 551 patients （51.6%） had a BARD score of ≥2. ConclusionThere is a relatively high prevalence rate of MAFLD among the health check-up population in Beijing， but with a relatively low number of patients with a high risk of advanced fibrosis， and such patients need to be referred to specialized hospitals for liver diseases.

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective:To explore the clinical efficacy and safety of endoscopic multi-band ligation (EMBL) in the management of refractory gastroesophageal reflux disease (RGERD) combined with esophageal hiatal hernia (HH).Methods:This study was a prospective, multicenter, small-sample cohort study. Patients who were diagnosed as having RGERD combined with HH at Inner Mongolia Medical University Cancer Hospital and Inner Mongolia Medical University Hospital from January 2020 to June 2022 were selected to undergo EMBL. The 24-hour esophageal pH monitoring and high-resolution manometry (HRM) related indicators, gastroesophageal reflux index (GERI), gastroesophageal reflux disease questionnaire (GERD-Q) scores, and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores were compared before and after the operation. The patient satisfaction and complications were also investigated.Results:A total of 25 patients were included, all of whom were successfully treated with EMBL. Reflux symptoms were relieved to varied degrees in all patients. There were no serious complications during or after the operation, such as perforation, bleeding, and dysphagia. Postoperative follow-up at 6 and 12 months showed a significant decrease in DeMeester scores [18.00 (5.83, 54.75) points, 16.30 (4.38, 60.00) points] compared to preoperative baseline [105.00 (60.80, 147.70) points, Z=-3.72, P<0.001; Z=-3.82, P<0.001]. The percentage of time of pH<4 [8.80 (6.10, 11.80)%, 8.95 (5.15, 10.90)%] significantly decreased compared to the baseline [31.15 (16.75, 54.75)%, Z=-3.72, P<0.001; Z=-3.72, P<0.001], the number of long refluxes [7.90 (4.93, 11.75) times, 6.90 (4.00, 10.75) times] significantly decreased compared to the baseline [33.00 (13.00, 43.00) times, Z=-3.82, P<0.001; Z=-3.58, P<0.001], and the number of acid refluxes (14.86±8.71 times, 12.93±5.51 times) significantly decreased compared to before (30.42±17.99 times, t=5.88, P<0.001; t=4.79, P<0.001). Lower esophageal sphincter resting pressure [9.70 (5.80, 19.58) mmHg, 11.70 (5.40, 19.78) mmHg] was significantly higher compared to before [4.70 (3.25, 7.00) mmHg, Z=-2.84, P<0.001; Z=-3.10, P<0.001]. GERD-Q scores (10.00±2.01 points, 9.43±1.74 points) were significantly higher compared to before (15.34±1.51 points, t=8.90, P<0.001; t=9.87, P<0.001), GERD-HRQL scores [7.00 (5.00, 7.75) points, 6.00 (5.75, 8.25) points] significantly decreased compared to preoperative baseline [13.50 (11.00, 21.25), Z=-3.73, P<0.001; Z=-3.72, P<0.001], and GERI (2.26%±1.58%, 2.07%±1.17%) significantly decreased compared to before (5.72%±2.27%, t=8.92, P<0.001; t=9.86, P<0.001). At 6 and 12 months postoperative follow-up, patient satisfaction [68.00% (15/25), 84.00% (21/25)] significantly increased compared to before [0.00% (0/25), Z=-4.63, P<0.001; Z=-6.48, P<0.001]. Conclusion:Preliminary small-sample study has shown that EMBL is safe, reliable and effective for the treatment of RGERD with HH.

The development of bio-psycho-social medical models has focused attention on the impact of chronic psychological stress on diseases.Chronic psychological stress falls within the category of emotional etiology in traditional Chinese medicine.This paper systematically reviews research progress into the chronic psychological stress-related combination of disease and syndrome,and analyzes the advantages and limitations of different models.We also provide insights into the direction and improvements of future research into chronic psychological stress-related disease pattern models.

Objective:To explore patterns of traditional Chinese medicine (TCM) use among patients with inflammatory bowel disease (IBD) in Jiangsu Province, China from 2019 to 2023.Methods:Using data from the IBD health data platform of the National Healthcare Big Data (Eastern) Center, a retrospective cohort study was conducted. We performed descriptive analyses on hospitalised patients diagnosed with IBD between 2019 and 2023, who received TCM treatment.Results:The study included 11 095 case records from 4 760 patients, with TCM diagnoses primarily indicating diarrhoea and abdominal pain. Ulcerative colitis (UC) accounted for 4 782 hospitalizations (3 103 patients), while Crohn's disease (CD) accounted for 6 313 hospitalizations (1 657 patients). Patient demographics showed a trend towards younger age and a higher proportion of males. Treatment utilisation was highest in southern Jiangsu compared with the central and northern regions. In terms of disease burden, all treatment costs showed a downward trend. In terms of external TCM therapies, UC patients tend to prefer plasters and enemas, while CD patients are more inclined to use acupuncture. Regarding herbal medicine, licorice, white atractylodes, and white peony root are commonly used single herbs for IBD patients.Conclusions:The number of IBD patients treated with TCM in Jiangsu Province has steadily increased from 2019 to 2023. It is important to identify effective TCM treatment methods to reduce the burden of patients.

Objective:To evaluate the value of D-dimer(D-D) levels in the diagnosis of thromboembolism in children with severe Mycoplasma pneumoniae pneumonia (SMPP).Methods:A case control study was conducted on 51 SMPP patients admitted to Qingdao Women and Children′s Hospital Affiliated to Qingdao University and Jining First People′s Hospital from January 1, 2021 to August 1, 2024.They were divided into a thrombus group (19 cases) and a non-thrombus group (32 cases) according to whether they had thromboembolism.The characteristics of the cases were analyzed.Logistic regression was used to analyze the relationship between increased D-D levels and the risk of thrombosis.The value of D-D levels in predicting thromboembolism in SMPP patients was evaluated by the receiver operating characteristic curve.Results:Of the 19 patients with thrombosis, 11 had with pulmonary thrombosis, 6 had cerebrovascular thrombosis, 3 had heart thrombosis, 1 had spleen artery thrombosis, and 3 had multiple site thrombosis.Compared with the non-thrombus group, the thrombus group had higher D-D levels[(18.5±4.9) mg/L vs.(3.1±0.8) mg/L, t=3.118, P=0.006], higher C-reactive protein levels[25.5(15.5, 92.7) mg/L vs.7.9(3.9, 21.4) mg/L, Z=3.292, P=0.001], higher lactate dehydrogenase levels[484(351, 743) U/L vs.347(285, 396) U/L, Z=2.770, P=0.006] and a higher proportion of pleural effusion[63.1%(12/19) vs.25.0%(8/32), χ2=7.282, P=0.009].Increased D-D levels were an independent risk factor for thromboembolism in SMPP patients ( P=0.005, OR=1.254, 95% CI: 1.069-1.472).When the D-D level was used for predicting thromboembolism in SMPP patients, its cut-off value was 4.46 mg/L, its Youden index was 0.707, its area under the curve was 0.893(95% CI: 0.807-0.979), its sensitivity was 89.5%, its specificity was 81.2%, and its negative predictive value was 92.9%. Conclusions:D-D levels have high value in predicting thromboembolism in SMPP patients, and it can help timely identify patients at high risk.