ObjectiveTo investigate the relationship between Jiaotai pill (JTP), its main component berberine (BBR), and the serotonin (5-HT) system in regulating islet hormone secretion and alleviating pancreatic β-cell dysfunction during type 2 diabetes mellitus (T2DM) progression.MethodsT2DM rat model was established using a high-fat diet and streptozotocin injection. JTP, BBR, and Metformin were intragastrically administered for 35 days. The analyzed indices included blood glucose, blood lipids, islet hormones, and proteins related to 5-HT synthesis, secretion, and transport. Additionally, an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1 (TPH1) inhibition.ResultsJTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats. Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion. However, the administration of JTP and BBR reversed these effects. Furthermore, JTP and BBR upregulated the expression of TPH1(P = .0194, P = .0413) transglutaminase 2 (TGase2; P = .0492, P = .0349), serotonin transporter (SERT, P = .0090), and 5- hydroxytryptamine 1F receptor (5-HT1FR) in the islet 5-HT pathway (P = .0194). In the cell model, the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition (P = .001), suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.ConclusionThe islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM. JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

Objective To investigate the expression of serum circPTP4A2 and circFOXP1 and their relationship with prognosis in patients with acute ischemic stroke(AIS).Methods The clinical data of 132 AIS patients(AIS group)and 140 healthy subjects(normal control group)were collected.The expression levels of serum circPTP4A2 and circFOXP1 in the two groups were detected by quantitative reverse transcription PCR(qRT-PCR).According to the NIHSS score at 24 h after admission,the patients were divided into mild group(＜4 points),moderate group(4-15 points),and severe group(＞15 points).According to the mRS score at 90 d of follow-up,the patients were divided into good prognosis group(≤2 points)and poor prognosis group(＞2 points).The Pearson method was applied to analyze the correlation between the expression levels of serum circPTP4A2 and circFOXP1 with the degree of AIS.Multivariate Logistic regression was applied to analyze the factors influencing the prognosis of AIS patients.ROC curve was applied to analyze the predictive value of serum circPTP4A2 and circFOXP1 expression for the prognosis of AIS patients,and the comparison of areas under curve(AUC)was performed through Z-test.Results Compared with those in normal control group,the level of serum circFOXP1 in the AIS group was significantly decreased,and the level of circPTP4A2 was significantly increased(all P＜0.001).There were significant differences in the levels of serum circPTP4A2 and circFOXP1 among the mild group,the moderate group and the severe group(F=151.235,P＜0.001;F=178.161,P＜0.001).Compared with those in mild group,the levels of serum circPTP4A2 in the moderate group and severe groups were significantly increased,and the levels of circFOXP1 were significantly decreased(all P＜0.05).Compared with those in moderate group,the level of serum circPTP4A2 in the severe group was significantly increased,and the level of circFOXP1 was significantly decreased(all P＜0.05).The level of serum circPTP4A2 was positively correlated with the severity of AIS(r=0.447,P＜0.001),and the level of serum circFOXP1 was negatively correlated with the severity of AIS(r=-0.412,P＜0.001).Compared with those in good prognosis group,the infarct volume,NIHSS score and serum circPTP4A2 level in the poor prognosis group were significantly increased,and the serum circFOXP1 level was significantly decreased(all P＜0.001).Multivariate Logistic regression analysis showed that circPTP4A2 was a risk factor for poor prognosis in AIS patients(OR=2.217,95％CI:1.429-3.439,P＜0.001),and circFOXP1 was a protective factor(OR=0.466,95％CI:0.295-0.737,P=0.001).The combined prediction of serum circPTP4A2 and circFOXP1 for poor prognosis was better than that of individual prediction(Z=2.532,P=0.011;Z=3.668,P=0.000).Conclusion The level of serum circPTP4A2 in AIS patients is increased,and the level of serum circFOXP1 is decreased,both of them have certain predictive value for the prognosis of AIS patients.

Objective:To explore the correlation among SMAD4 gene polymorphisms, early life traumatic experience and their interactions with clinical feature of obsessive-compulsive disorder (OCD). Methods:Totally 484 OCD patients who met the DSM-Ⅳ diagnostic criteria and 368 health controls who met the enrollment criteria were recruited from September 2013 to September 2018. The Yale-Brown obsessive-compulsive scale (Y-BOCS) was used to assess the severity of obsessive-compulsive symptoms, the Beck depression inventory Ⅱ (BDI-Ⅱ) was used to assess the severity of depressive symptoms, the Beck anxiety inventory (BAI) was used to assess the severity of anxiety symptoms, and early trauma inventory-short form (ETI-SF) was used to assess early traumatic experience. SMAD4: rs12452684, rs2276163, rs17663887 and rs3819122 were genotyped using the Taqman genotyping technique. Data were analyzed using SPSS 20.0 software, and comparisons among groups were performed using chi-square test, t-test, Mann-Whitney U non-parametric test and analysis of covariance. Correlation was analyzed using Spearman correlation analysis, and interactions were analyzed using general linear model. Results:All sites except rs17663887 met the Hardy-Weinberg equilibrium (rs12452684: χ2=0.29, P=0.59; rs2276163: χ2=2.58, P=0.11; rs3819122: χ2=0.22, P=0.64).Allele, genotype frequencies of SMAD4: rs12452684, rs2276163 and rs3819122 were not statistically significant between the OCD and the health control groups ( χ2=0.02, 1.20, 0.04, all P>0.05; χ2=1.85, 3.98, 1.45, all P>0.05). The results of covariance analysis (corrected for age and gender) showed that there were significantly differences in compulsion (CC: 12.47±4.23, CT: 12.53±4.15, TT: 13.97±3.11; AA: 12.63±4.08, AC: 12.49±4.19, CC: 13.87±2.93) and total Y-BOCS scores(CC: 25.31±6.42, CT: 25.68±5.90, TT: 27.75±6.01; AA: 25.54±6.52, AC: 25.56±5.98, CC: 27.63±5.75) among the three genotypes of the SMAD4: rs2276163 and rs3819122 between the two groups ( F=3.58, 3.87, 3.48, 3.73, all P<0.05). Emotional abuse in the ETI-SF was positively correlated with obsession and total Y-BOCS scores( r=0.14, 0.14, both P<0.05). The interactions of rs2276163, rs3819122 and emotional abuse were associated with obsession scores ( F=4.65, 3.63, 2.93, all P<0.01). Conclusions:The more emotional abuse experienced in early life, the more severe obsessive-compulsive symptoms, and the interaction between the SMAD4 gene and early traumatic experience is involved in the development of OCD.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

Objective:To investigate the essential determinants that are critical to initiating the assembly of outer membrane proteins by replacing the POTRA domains of the translocator protein FhaC and the insertase protein TtOmp85 of the Omp85 family. Methods:FhaC, TtOmp85 proteins and their recombinant chimeric proteins after replacing the POTRA domain were obtained by overexpression and purification in vitro. An in vitro reconstitution system was used to investigate the effects of the different domains on the transport efficiency of the substrate outer membrane protein FhaB and the membrane insertion efficiency of OmpA. Results:Replacing the POTRA domain of FhaC with that of TtOmp85 led to the loss of the transport function of FhaB. During the membrane insertion process of OmpA, the FhaC mutant containing the POTRA of TtOmp85 protein acquired the ability to assemble OmpA. Conclusion:The compositional differences in the POTRA domain of Omp85 family proteins determine their abilities to recognize their substrate proteins.

Objective:To explore the latent profiles of cognitive function in older adults with mild cognitive impairment(MCI)and to analyze the influencing factors, as well as to develop targeted interventions.Methods:The data for this study were obtained from a cross-sectional study conducted from May to December 2023.Peterson's criteria and the Chinese guidelines for the diagnosis and treatment of dementia and cognitive impairment(V)were employed to screen for MCI among 1, 650 elderly individuals aged 60 and above in a specific community.The Montreal Cognitive Assessment Scale(MoCA)and the Centre for Epidemiological Studies Depression Scale(CES-D)were utilized to assess cognitive ability and depression levels, respectively.Serum vitamin D3 levels were measured using mass spectrometry.Potential profile models of cognitive function in MCI patients were analyzed using Mplus 8.3, and the influencing factors of the latent profiles were identified through multivariate logistic regression.Results:A total of 327 older adults with MCI were initially screened, revealing a prevalence rate of 19.82%.Out of these, 295 patients were ultimately included in the study.The cognitive impairment of these participants was categorized into three profiles: the mild low-cognitive group(49.15%), the mild low-cognitive with severely low-abstraction group(41.70%), and the severely low-cognitive group(9.15%).Logistic regression analysis identified several independent predictors for the severely low-cognitive group among older adults with MCI: education level(primary and below compared to high school and above: OR=7.343, P<0.001; junior high compared to high school and above: OR=1.689, P=0.004), depression level( OR=1.120, P=0.002), and napping habits(with napping habits compared to without: OR=0.255, P=0.006).Additionally, education level( OR=3.535, P<0.001), depression level( OR=1.125, P<0.001), and serum vitamin D3 levels( OR=0.811, P=0.035)were found to be independent predictors for the mild low-cognitive with severely low-abstraction group in older adults with MCI. Conclusions:Cognitive impairment in older adults with MCI exhibits heterogeneity, which can be categorized into three potential profiles.Targeted interventions should be implemented based on the characteristics and influencing factors of each category to mitigate cognitive decline among older adults with MCI.

Objective:To investigate the association between triglyceride glucose index (TyG) and early vascular aging measured by brachial ankle pulse wave velocity (baPWV) in young and middle-aged population.Methods:It was a cross-sectional study. A total of 5 680 subjects aged 20 to 59 years who underwent health check-ups at the Health Management Center of General Hospital of Tianjin Medical University from January to December in 2020 were selected as the research subjects. All the research subjects completed the health risk assessment questionnaire, physical examination, laboratory test, and multi-functional vascular lesion detection. The TyG was calculated and the research subjects were divided into four groups with the quartiles of TyG (Q 1 to Q 4, with a cut-off value of 8.22, 8.60 and 9.01, respectively). The baPWV value was converted into a Z-score, and those with a Z-score above the 95th percentile were defined as having early vascular aging. The Spearman correlation method, multiple linear regression model, binary logistic regression model and the area under the receiver operating characteristic curve (AUC) were used to analyze the association between TyG and early vascular aging. Results:Among the 5 680 middle-aged and young people included in the analysis, there were 3 117 males and 2 563 females, with an age of 46 (39, 52) years, a TyG of 8.60 (8.22, 9.01), and a baPWV of 1 279.25 (1 147.50, 1 434.25) cm/s. The prevalence rate of early vascular aging was 5.02% (285/5 680). Taking group Q 1 as the reference, in the multiple linear regression model adjusted for multiple factors, group Q 4 was significantly associated with a 47.64 (95% CI: 28.18-67.11) cm/s increase in baPWV ( P for trend<0.001). In the multivariate adjusted binary logistic regression model, compared with that in the Q 1 group, the OR of early vascular aging occurrence in the Q 2, Q 3, and Q 4 groups was 1.52 (95% CI: 0.75-3.07), 1.78 (95% CI: 0.89-3.58), and 3.04 (95% CI: 1.47-6.31), respectively. Elevated TyG level was positively correlated with the occurrence of early vascular aging ( P for trend<0.001). The AUC of TyG in predicting early vascular aging was 0.732 (95% CI: 0.704-0.759), with the optimal cut-off value being 8.86. The AUC of TyG in predicting early vascular aging in males was lower than that in females [0.665 (95% CI: 0.628-0.702) vs 0.796 (95% CI: 0.748-0.843)] ( P<0.001). Conclusions:There is a correlation between TyG and early vascular aging measured by baPWV in the middle-aged and young population. When TyG≥8.86, clinical intervention measures should be taken in a timely manner.

Aim To investigate the effects of m6A demethylase ALKBH5 on cardiomyocytes pyroptosis in mice with myocardial infarction(MI).Methods The MI model of left anterior descending coronary artery ligation surgery was established by knocking down ALKBH5 using adeno-associated virus,and the hypox-ia model of mouse cardiomyocytes(HL-1)was estab-lished by knocking down small interfering RNA.The effects of ALKBH5 on the pyroptosis of MI mice and hypoxic HL-1 cells were observed.Subsequently,mechanism studies were conducted at the cellular lev-el,and the binding of ALKBH5 and IGF2BP2 to NL-RP3 mRNA was detected through RNA pull down and RNA immunoprecipitation(RIP)experiments.The MeRIP-qPCR method was used to determine the effects of ALKBH5 on the mRNA m6A level of NLRP3.Acti-nomycin D for RNA stability experiments were conduc-ted to detect the effects of ALKBH5 and IGF2BP2 on the stability of NLRP3 mRNA.Results Knocking down ALKBH5 in vivo and in vitro both inhibited NL-RP3 inflammasome activation and alleviated pyroptosis in MI mice and hypoxic HL-1 cells.Mechanistically,the results showed that NLRP3 mRNA could bind to ALKBH5 protein in HL-1 cells;knocking down ALK-BH5 could increase the m6A level of NLRP3 and re-duce the stability of NLRP3 mRNA;subsequently,it was confirmed that NLRP3 mRNA and IGF2BP2 pro-tein bound to each other;knocking down IGF2BP2 in-creased the mRNA stability of NLRP3.The Rescue ex-periment showed that knocking down IGF2BP2 re-versed the decrease in NLRP3 mRNA expression caused by knocking down ALKBH5.Conclusions ALKBH5 mediated m6A modification of NLRP3 pro-motes cardiomyocytes pyroptosis in mice with myocardi-al infarction.