ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

Objective:To investigate the impact of geometric morphology and hemodynamic characteristics at the carotid bifurcation on the formation of ulcerated plaques based on CT angiography(CTA).Methods:This was a cross-sectional study. The clinical and imaging data of 71 patients with carotid bifurcation atherosclerotic plaques (stenosis≥50%) confirmed by cranial and cervical CTA at Tianjin TEDA Hospital from July 2020 to October 2023 were retrospectively analyzed. Patients were divided into an ulcerated plaque group (32 cases) and a non-ulcerated plaque group (39 cases) based on plaque ulceration status. The CTA technique was used to assess the geometric parameters of the carotid bifurcation [such as the bifurcation angle, the angle between the common carotid artery and internal carotid artery (CCA-ICA), the proximal curvature angle of the internal carotid artery (ICA), and the ratio of the maximum area at the carotid bifurcation to the initial area of the carotid artery (CCAMAX/CCA)] and plaque characteristic parameters [such as plaque area at the site of stenosis, maximum wall thickness, remodeling ratio, eccentricity index, and presence of calcification within plaques]. Quantitative analysis of hemodynamic parameters in the plaque region was performed using finite-element analysis software, including time-averaged wall shear stress (TAWSS), transverse wall shear stress (transWSS), relative residence time (RRT), and oscillatory shear index (OSI). Comparisons of parameters between the two groups were conducted using the Mann-Whitney U test or χ2 test, and multivariate logistic regression analysis was employed to identify independent geometric and plaque characteristic factors influencing the formation of ulcerated plaques. A combined model incorporating hemodynamic, geometric, and plaque characteristic parameters was developed, and the efficacy of this combined model in predicting ulceration formation at the carotid bifurcation was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:The bifurcation angle, CCA-ICA angle, proximal ICA curvature angle, CCAMAX/CCA ratio, presence of calcification within plaques, plaque area at the site of stenosis, and maximum wall thickness exhibited statistically significant differences between the ulcerated plaque group and the non-ulcerated plaque group ( P<0.05). Logistic regression analysis showed that CCAMAX/CCA ( OR=6.452, 95% CI 1.541-27.015, P=0.011) and plaque area at the site of stenosis ( OR=1.048, 95% CI 1.015-1.124, P=0.011) were independent factors influencing the formation of ulcerated plaques at the carotid bifurcation. The maximum and mean values of RRT and OSI in the ulcerated plaque group were significantly higher than those in the non-ulcerated group ( P<0.05), while the maximum and mean values of transWSS and TAWSS were lower in the ulcerated group compared to the non-ulcerated group ( P<0.05). The AUC for the combined model predicting ulceration formation at the carotid bifurcation was 0.926. Conclusions:The CCAMAX/CCA ratio and plaque area at the site of stenosis at the carotid bifurcation are independent factors influencing the formation of ulcerated plaques. A model that combines geometric morphology and hemodynamic parameters can more effectively diagnose the formation of ulcerated plaques at the carotid bifurcation.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

Objective To observe the effects of general anesthesia with remazolam on electrophysiological monitoring indicators and cerebral oxygen saturation(ScO2)in patients undergoing carotid endarterectomy(CEA).Methods Patients who underwent elective CEA from July 2022 to June 2024 in neurosurgery department of our hospital were randomly divided into the ramazolam group(R group)and the propofol group(P group).Patients in both groups were given propofol 1.5 to 2.0 mg/kg,cisatracurium 0.1 to 0.2 mg/kg,and sufentanil 0.3 to 0.4 μg/kg for anesthesia induction.Anesthesia maintenance:patients in the R group received intravenous infusion of remifentanil 0.5 to 1.0 mg·kg-1·h-1,while patients in the P group received intravenous infusion of propofol 5.0 to 7.0 mg·kg-1·h-1.Both groups received intravenous infusion of remifentanil 0.1 to 0.2 μg·kg-1·min-1 for anesthesia maintenance.The operation time,carotid artery occlusion time,intraoperative infusion volume,remifentanil and norepinephrine dosage,and awakening time of patients in the two groups were recorded.The hemodynamic and cerebral oxygen indicators,amplitude and latency of evoked potentials before anesthesia(T0),after anesthesia(T1),5 minutes before blockade(T2),5 minutes after blockade(T3),5 minutes after unblocking(T4)and at the end of surgery(T5)of patients in the two groups were observed and compared,and the total incidence of postoperative complications was followed up and calculated.Results Compared with the P group,the dosage of intraoperative norepinephrine of patients in the R group was reduced(P<0.05),and the awakening time was shortened(P<0.05).At T2,the average arterial pressure(MAP)of patients in the R group was higher than that in the P group(P<0.05).At T3,the ScO2 of patients in the R group was significantly higher than that in the P group,and the percentages of prolonged latency and decreased amplitude of motor evoked potentials(MEP)were significantly lower than those in the P group(P<0.05),the percentage of decreased amplitude of lower limb somatosensory evoked potentials(SSEP)was lower than that in the P group(P<0.05);At T5,the MEP amplitude of patients in the R group was significantly increased compared to that at T2,while the MEP amplitude of patients in the P group was significantly decreased compared to that at T2,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the total incidence of postoperative complications between the two groups(P>0.05).Conclusion As a general anesthesia maintenance drug,remazolam can achieve satisfactory anesthesia effects for CEA,with more stable intraoperative hemodynamics,and less impact on ScO2 and evoked potential monitoring during carotid artery occlusion compared to propofol,resulting in higher safety.

Objective:To investigate the drug resistance gene characteristics, plasmid characteristics and genome tracing of Shigella sonnei causing a bacillary dysentery outbreak in Shandong Province. Methods:Sixty-five Shigella sonnei strains isolated from a 2021 outbreak in a county of Shandong Province were analyzed using antimicrobial susceptibility testing, whole genome sequencing (WGS), characterization of resistance and virulence genes, plasmid profiling, core genome multilocus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis. Results:All isolates had the same resistance phenotype and genotypes and were multidrug-resistant ESBL-producing Shigella sonnei, carrying important virulence genes. Plasmid analysis revealed a conserved genetic arrangement, pil( M/ N/ O2/ P)-tra( F/ H/ J/ K/ N/ O/ P/ Q)-IS Ecp1- blaCTX-M-14-Tn 903- yub( J/ I/ F/ G/ E/ D), and shared across strains from diverse regions and bacterial species. The cgMLST and SNP analyses demonstrated concordant clustering, with all 65 outbreak-related strains forming a single cluster alongside human-derived strains from Guangxi. Conclusion:The ESBL-producing Shigella sonnei responsible for the outbreak shares a homologous relationship with Guangxi human-derived strains, and the detected resistance plasmids and virulence genes underscore the need to strengthen drug resistance surveillance and genome tracing.

Objective To explore the relationship between continuous glucose monitoring(CGM)parameters with diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 355 T2DM patients who were hospitalized in the Department of Endocrinology of Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,from August 2022 to February 2024 were included.According to uninary albumin/creatinine rate(UACR)and estimated glomerular filtration rate(eGFR)levels,the patients were divided into T2DM group(n=207)and DKD group(DKD,n=148).The general clinical data and CGM parameters of the two groups were compared.Results Age,systolic pressure,DM duration,proportion of Ins use,proportion of cerebral infarction and lumen infarction,proportion of lower limb arterial plaque formation,serum troponin I,D-dimer,erythrocyte deposition rate,UACR,blood urea nitrogen(BUN),serum creatinine,blood uric acid,mean glucose value(MG),blood glucose management index(GMI),time glucose below target range(TBR),glucose above target range time(TAR)and mean blood glucose fluctuation range(MAGE)were higher than those in T2DM group(P<0.05),while the proportion of fatty liver,eGFR,total bilirubin,direct bilirubin,indirect bilirubin,alanine aminotransferase,white ball ratio of liver function and TIR were lower than those in T2DM group(P<0.05).Pearson and spearman correlation analysis showed that HbA1c was negatively correlated with TIR(P<0.05),and positively correlated with TAR,MG,FPG,GMI,coefficient of variation,standard deviation,maximum blood glucose fluctuation and MAGE(P<0.05).Logistic regression analysis showed that TIR(OR 1.029,95%CI 1.012～1.047)and TAR(OR 0.974,95%CI 0.958～0.990)were the influencing factors for DKD in T2DM patients.ROC curve analysis showed that the area under the curve predicted by TIR for DKD was 0.651,with the sensitivity 64.2%,the specificity 60.9%,and the truncation value 53.46%.Conclusions TIR and TAR are the influencing factors of DKD in T2DM patients,and other CGM indicators such as MG,GMI and MAGE are related to HbA1c.

Aim To investigate the intervention effect of Rehmannia radix water extract on bleomycin(BLM)-induced pulmonary fibrosis in mice combined with metabolomics and to reveal the potential mechanism,in order to provide new ideas for clinical treatment of pul-monary fibrosis.Methods Male C57BL/6N mice were randomly divided into the control group,model group,pirfenidone group(positive control,PFD,270 mg·kg-1),and low dose(DH-L,4.55 g·kg-1)group,medium dose(DH-M,9.1 g·kg-1)group and high dose(DH-H,18.2 g·kg-1)group of Rehman-nia.Except for the control group,BLM(5 mg·kg-1)was instilled into the trachea to establish the model of pulmonary fibrosis in the other groups.The survival rate,lung index and blood oxygen saturation of mice in each group were evaluated.HE and Masson staining were used to observe the pathological changes of lung tissue.WBP was used to detect lung function.Flow cytometry was used to detect the apoptosis of primary lung cells,ROS and immune cells.ELISA was used to detect the levels of fibrosis markers and inflammatory factors(α-SMA,collagen Ⅰ,collagen Ⅲ,TGF-β1,TNF-α,IL-1 β,and IL-6).Biochemical method was employed to detect the contents of GSH-Px,T-SOD and MDA.Liquid chromatograph mass spectrometer(LC-MS)metabolomics was used to analyze the changes of serum metabolic profile.Results Water extract of Re-hmannia significantly increased the survival rate,oxy-gen saturation and lung function of mice with pulmona-ry fibrosis,reduced the lung coefficient,ameliorated pathological damage and collagen deposition in lung tissue,reduced the levels of apoptosis and oxidative stress,and down-regulated the levels of inflammatory factors in lung tissue.It regulated the levels of metabo-lites such as bile acid metabolism,sphingolipid metabo-lism,and unsaturated fatty acid metabolism.Conclu-sions Water extract of Rehmannia inhibits lung injury and collagen deposition in mice with pulmonary fibrosis by inhibiting inflammatory response,which may be a-chieved by regulating the levels of inflammatory factors through the metabolic pathways of bile acid and sphin-golipid.

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.

Objective:To investigate the longitudinal patterns and influencing factors of platelet counts among healthy adults in Sichuan Province from 2010 to 2021, and to inform the establishment of region-specific reference intervals for platelet counts.Methods:This study is a retrospective study. A total of 7 808 healthy adults who underwent annual physical examinations at West China Hospital, Sichuan University, between January 2010 and December 2021 were included. All participants were permanent Chengdu residents and completed consecutive complete blood count tests. Group-based trajectory modeling (GBTM) was used to identify distinct trajectories of platelet count over the ten-year period. One-way analyses were then conducted to compare baseline demographic characteristics (sex and age) among the different trajectory groups.Results:Among 7 808 participants, 4 589 (58.8%) were male and 3 219 (41.2%) were female. Four platelet count trajectories were identified by GBTM: steadily increasing group [27.4% (2 139/7 808)], early increase-plateau group [44.1% (3 445/7 808)], early decrease-subsequent increase group [5.4% (422/7 808)], and steadily decreasing group [23.1% (1 802/7 808)], with an average growth rate of 3.3%, 1.6%, 0.7%, and -0.6%, respectively. There were statistically significant differences in both sex and age distributions among the four trajectory groups. Sex-distribution differed significantly across the four trajectory groups ( χ2=73.3, P<0.001). The male proportions in the four trajectory groups were 59.6% (1 275/2 139), 62.8% (2 165/3 445), 48.1% (203/422), and 52.5% (946/1 802), respectively. The baseline ages were 45 (36, 55), 43 (35, 53), 50 (40, 60), and 47 (39, 58) years, respectively (H=121.0, P<0.001). Conclusions:Healthy adults in Sichuan Province exhibit four longitudinal trajectories of platelet counts: steadily increasing, early increase-plateau, early decrease-subsequent increase, and steadily decreasing. The two trajectories characterized by rising platelet counts (steadily increasing group and early increase-plateau group) exhibited higher male predominance and lower median ages, whereas the early decrease-subsequent increase group and the steadily decreasing group exhibited lower male proportions and higher median ages. Therefore, while establishing reference intervals and developing health management strategies for platelet counts, it is essential to account for the sex, age characteristics and the population′s dynamic changes.

Objective To explore the relationship between continuous glucose monitoring(CGM)parameters with diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 355 T2DM patients who were hospitalized in the Department of Endocrinology of Wuhan Central Hospital,Tongji Medical College,Huazhong University of Science and Technology,from August 2022 to February 2024 were included.According to uninary albumin/creatinine rate(UACR)and estimated glomerular filtration rate(eGFR)levels,the patients were divided into T2DM group(n=207)and DKD group(DKD,n=148).The general clinical data and CGM parameters of the two groups were compared.Results Age,systolic pressure,DM duration,proportion of Ins use,proportion of cerebral infarction and lumen infarction,proportion of lower limb arterial plaque formation,serum troponin I,D-dimer,erythrocyte deposition rate,UACR,blood urea nitrogen(BUN),serum creatinine,blood uric acid,mean glucose value(MG),blood glucose management index(GMI),time glucose below target range(TBR),glucose above target range time(TAR)and mean blood glucose fluctuation range(MAGE)were higher than those in T2DM group(P<0.05),while the proportion of fatty liver,eGFR,total bilirubin,direct bilirubin,indirect bilirubin,alanine aminotransferase,white ball ratio of liver function and TIR were lower than those in T2DM group(P<0.05).Pearson and spearman correlation analysis showed that HbA1c was negatively correlated with TIR(P<0.05),and positively correlated with TAR,MG,FPG,GMI,coefficient of variation,standard deviation,maximum blood glucose fluctuation and MAGE(P<0.05).Logistic regression analysis showed that TIR(OR 1.029,95%CI 1.012～1.047)and TAR(OR 0.974,95%CI 0.958～0.990)were the influencing factors for DKD in T2DM patients.ROC curve analysis showed that the area under the curve predicted by TIR for DKD was 0.651,with the sensitivity 64.2%,the specificity 60.9%,and the truncation value 53.46%.Conclusions TIR and TAR are the influencing factors of DKD in T2DM patients,and other CGM indicators such as MG,GMI and MAGE are related to HbA1c.