The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

ObjectiveTo explore the compliance related factors of repeated screening for colorectal cancer in Jiading District， and to provide a scientific basis for the prevention and control of colorectal cancer. MethodsBased on the natural population cohort in Jiading District， and the screening situation in 2017‒2019 and 2020‒2022， the study subjects were divided into the groups of never participating in screening and participating in screening. Subjects in the participating group were further divided into participating in one round of screening or having repeated screening. SPSS 21.0 software was used to analyze the demographic characteristics of each group. χ² test or Fisher precise probability test were used to conduct univariate analysis of the factors such as gender， age， education level， marital status， retirement status， and type of medical insurance. Factors with the significant difference （P<0.05） were selected for inclusion in multivariate analysis， and factors related to compliance with repeated screening were analyzed by multivariate logistic regression. ResultsA total of 8 179 subjects were included in the study， including 3 323 males （40.6%） and 4 856 females （59.4%）. The average age of the subjects was （61.26±6.06） years old. A total of2 652 （32.4%） had educated in primary school or below， 4 242 （51.9%） in secondary school， and 1 285 （15.7%） in higher secondary school. Mostly， 7 579 （92.7%） were married. Among the participants， 4 062 people had never participated in screening， 4 117 people had participated in screening， and 1 485 of them had repeated screening， with a repeated screening rate of 18.2%. Multivariate logistic regression analysis showed that women had better compliance with repeated screening than men （OR=1.31， 95%CI： 1.14‒1.50）. Compared with the population aged 50 to 54 years， the population aged 55‒59 years （OR=1.57， 95%CI： 1.19‒2.08）， 60-64 years （OR=2.77， 95%CI： 2.13‒3.61）， and 65-69 years （OR=3.31， 95%CI： 2.51‒4.36） had higher compliance with repeated screening. Compared with employees' medical insurance， residents' medical insurance group had worse compliance with repeated screening （OR=0.76， 95%CI： 0.66‒0.87）. People with a history of intestinal polyps were more likely to undergo repeat screening than those without （OR=2.07， 95%CI： 1.50‒2.87）. ConclusionCompliance with repeated screening for colorectal cancer still needs to be improved， and there are differences in compliance with repeated screening for different populations with different characteristics. Identifying groups that are unlikely to adhere to community-based colorectal cancer screening and taking targeted interventions can help improve the continued compliance of residents with colorectal cancer screening.

Objective: To explore the relationship between processed food consumption and blood pressure level of students in a university in Yunnan Province, so as to provide the reference for preventing hypertension in university students. Methods: In October 2021, a cluster sampling method was used to select 4 781 freshmen from a university in Kunming, Yunnan Province. The frequency of processed food consumption of university students was assessed by using the dietary frequency questionnaire, and height, weight and blood pressure were measured. Mann-Whitney test and Kruskal-Wallis test were used to compare the differences in blood pressure level of university students with different demographic variables, and the association between processed food consumption and blood pressure level was analyzed with a generalized linear model. Results: Among the students of a university in Yunnan Province, the detection rates of systolic prehypertension and hypertension were 33.86% and 1.23%, and the detection rates of diastolic prehypertension were 32.13% and hypertension 7.22%. The results of generalized linear model analysis showed that after controlling for demographic variables and other variables that might affect the blood pressure level of university students, the consumption of processed food (bread and cake: β =0.15, 95% CI =0.01-0.29) and ultra processed food (coffee beverage: β =-0.29, 95% CI =-0.54--0.03) were associated with systolic blood pressure level( P <0.05). The consumption of processed food (salted duck egg: β =0.21, 95% CI =0.01-0.41) was correlated with the diastolic blood pressure of college students ( P <0.05). Conclusions Processed food consumption in university students may increase the risk of high blood pressure.The education of healthy eating among college students should be strengthened to reduce the consumption of processed foods.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

Objective:To investigate the associated factors of depressive symptoms among patients with neo-plasms.Methods:Nationwide(excluding Hong Kong,Macao,and Taiwan),30 505 residents were selected by a combination of stratified sampling and quota sampling according to the proportion of the seventh national population census.Patient Health Questionnaire-9(PHQ-9),General Anxiety Disorder-7(GAD-7),self-made questionnaire,and simplified perceived social support scale used to evaluate depressive symptoms,anxiety symptoms,behaviors,and perceived social support among patients with neoplasms.Results:Totally 359(1.2％)patients with self-repor-ted clinically diagnosed neoplasms were included,of which 151(42.1％)patients with malignant neoplasms and 208(57.9％)patients with benign neoplasms.The detection rate of depressive symptoms in patients with neo-plasms was 76.6％.Less than three days of walking for more than 10 minutes per day in the past week(OR=6.63),4-6 days of walking for more than 10 minutes per day in the past week(OR=5.00),the low(OR=4.80)or medium(OR=3.06)overall sleep quality,the lower perceived friend support(OR=4.66),and anxiety symp-toms(OR=1.74)among patients with neoplasms were risk factors for depressive symptoms.Conclusion:Patients with neoplasms generally might be at a high risk of depressive symptoms,especially for those patients with less ex-ercise,poor sleep quality,and low perceived social support.

Objective:To describe the prevalence of anxiety symptom and personality disorder among medical aesthetic clients,and explore related factors of anxiety symptoms among them.Methods:Totally 788 clients who consulted in a cosmetic plastic surgery department were recruited in a tertiary hospital in Beijing from November 2021 to July 2023.Using the Personality Diagnostic Questionnaire-4(PDQ-4)and the Self-Rating Anxiety Scale(SAS)as assessment instruments,with a cutoff point of 42 and 50 points respectively,for screening out personality disorder and anxiety symptom.Statistical analysis was conducted by analysis of variance,chi-square tests,multivari-ate linear regression and logistic regression.Results:The rate of anxiety symptom among the medical aesthetic cli-ents was of 15.23％(120/788),and the prevalence of personality disorder was 3.50％(28/788).Age was nega-tively associated with SAS scores(β=-0.82,P=0.009),PDQ-4 score was positively associated with SAS score(β=0.15,P＜0.001),eye plastic surgery,facial contouring and minimally invasive plastic surgery were positively associated with SAS score(β=2.00-3.64,P＜0.05).Conclusion:The younger and the more prominent the per-sonality dysfunction the clients are,the severer anxiety symptom they have.The clients who consult for eye plastic surgery,facial contouring,and minimally invasive plastic surgery have severer anxiety symptom.

Objective: To analyze the longitudinal association between mobile phone dependence and depressive symptoms in college students, so as to provide a theoretical basis for psychological health education among college students. Methods: From November 2021 to June 2023, 2 515 first year students from 2 universities in Yunnan Province were surveyed with a questionnaire by a cluster random sampling method, including baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The Self rating Questionnaire for Adolescent Problematic Mobile Phone Use and the Depression Anxiety Stress Scales-21 (DASS-21) were used to evaluate mobile phone dependence and depressive symptoms of college students. The χ 2 test was used to analyze the difference in depressive symptoms among different demographic groups, and a generalized estimation equation model was established to analyze the association between mobile phone dependence symptoms and depressive symptoms. Results: The detection rates of depressive symptoms among university students in Yunnan Province at time points T1, T2, T3, and T4 were 23.02%, 33.36%, 34.79% and 35.51%, respectively. There were statistically significant differences in the detection rates of depressive symptoms among college students with different sacademic burden (T1, T2, T3, T4), different number of close friends (T1, T2, T3), as well as their father s educational level (T1), mothers educational level (T2, T4), gender (T4), major (T3, T4), education (T2, T3, T4), family residency (T1, T2), and family economic conditions (T1, T2, T4) ( χ 2= 59.68 , 49.38, 16.70, 39.31; 55.35, 26.01, 16.69; 10.22; 14.87, 11.51; 14.90; 27.81, 50.28; 9.75, 7.42, 24.76; 6.06, 4.47 ; 15.88, 14.58, 15.85, P < 0.05 ). After controlling for demographic variables and confounding factors in the generalized estimation equation model, mobile phone dependence ( β =0.11), withdrawal symptoms of mobile phone dependence ( β =0.14), and the physical and mental effects of mobile phone dependence ( β =0.14) were all positively correlated with depressive symptoms ( P <0.01). Further gender analysis showed that depressive symptoms in both boys ( β =0.13, 0.13, 0.18) and girls ( β =0.10, 0.13, 0.13 ) were associated with mobile phone dependence, withdrawal symptoms of mobile phone dependence and the physical and mental effects of mobile phone dependence ( P <0.01). Conclusions Depressive symptoms of college students are positively correlated with mobile phone dependence, and family economic conditions, academic burden and number of close friends are factors that continued to affect depressive symptoms. College students should be guided to pay attention to the impact of excessive use of mobile phones on their physical and mental health, use mobile phones reasonably to reduce the incidence of depressive symptoms among college students.

OBJECTIVE To mine adverse drug event （ADE） signals of lacosamide， and to provide references for clinically safe drug use. METHODS ADE data for lacosamide reported to the United States FDA adverse event reporting system from January 1， 2009， to December 31， 2022， were collected. Data mining was conducted using the reporting odds ratio method and Bayesian confidence propagation neural network method. Classification statistics were performed using the system organ class （SOC） and preferred terms （PT） from ADE terminology set of Medical Dictionary for Regulatory Activities （Version 25.0）. RESULTS A total of 21 360 lacosamide ADE reports were received， identifying 203 ADE signals across 24 SOCs， with 19 signals not included in the drug’s instruction. The top five PTs ranked by occurrence frequency were medication overdose， technical errors during device use， product use issues， intentional product misuse， and therapy discontinuation. The top five PTs ranked by signal strength were changes in seizure presentation type， congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， brain surgery， and vagus nerve stimulator implantation. ADEs not recorded in the drug instruction included congenital hypoplasia of depressor anguli oris muscle， multidrug resistance， mitochondrial DNA mutation， dissociative identity disorder， and congenital auricular anomaly. CONCLUSIONS For lacosamide-induced ADEs that occur frequently and are already listed in the drug’s instructions， such as bradycardia and atrioventricular block， the clinical application should be careful and attentive， adjusting the dosage timely according to the patient’s condition to avoid severe ADEs. Newly discovered suspect ADEs， such as congenital hypoplasia of depressor anguli oris muscle， mitochondrial DNA mutation， overmature infant， dissociative identity disorder， pigmenturia， behavioral disorders， and dissociative disorders， should be vigilantly recognized to ensure the safety of drug use.