Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.

BACKGROUND:Primary osteoporosis has a high incidence,but the pathogenesis is not fully understood.Currently,there is a lack of effective early screening indicators and treatment programs. OBJECTIVE:To further explore the mechanism of primary osteoporosis through comprehensive bioinformatics analysis. METHODS:The primary osteoporosis data were obtained from the gene expression omnibus(GEO)database,and the differentially expressed genes were screened for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.In addition,the differentially expressed genes were subjected to protein-protein interaction network to determine the core genes related to primary osteoporosis,and the least absolute shrinkage and selection operator algorithm was used to identify and verify the primary osteoporosis-related biomarkers.Immune cell correlation analysis,gene enrichment analysis and drug target network analysis were performed.Finally,the biomarkers were validated using qPCR assay. RESULTS AND CONCLUSION:A total of 126 differentially expressed genes and 5 biomarkers including prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,transforming growth factor B1,and retinoblastoma gene 1 were obtained in this study.GO analysis showed that differentially expressed genes were mainly concentrated in the cellular response to oxidative stress and the regulation of autophagy.KEGG analysis showed that autophagy and senescence pathways were mainly involved.Immunoassay of biomarkers showed that prostaglandins,retinoblastoma gene 1,and mitogen-activated protein kinase 3 were closely related to immune cells.Gene enrichment analysis showed that biomarkers were associated with immune-related pathways.Drug target network analysis showed that the five biomarkers were associated with primary osteoporosis drugs.The results of qPCR showed that the expression of prostaglandins,epidermal growth factor receptor,mitogen-activated protein kinase 3,and transforming growth factor B1 in the primary osteoporosis sample was significantly increased compared with the control sample(P<0.001),while the expression of retinoblastoma gene 1 in the primary osteoporosis sample was significantly decreased compared with the control sample(P<0.001).Overall,the study screened and validated five potential biomarkers of primary osteoporosis,providing a reference basis for further in-depth investigation of the pathogenesis,early screening and diagnosis,and targeted treatment of primary osteoporosis.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To investigate the prevalence of Schistosoma japonicum infections in wild rodents in schistosomiasis-endemic areas of China, so as to provide insights into formulation of technical guidelines for monitoring of and the precise control strategy for S. japonicum infections in wild rodents during the elimination phase. Methods Two administrative villages where schistosomiasis was historically highly prevalent were selected each from Dongzhi County, Anhui Province, and Duchang County, Jiangxi Province as study villages. Wild rodents were captured from study villages with baited traps or cages at night in June and September, 2021. The number of rodents captured was recorded, and the rodent species was characterized based on morphologi-cal characteristics. Liver tissues were sampled from captured rodents for macroscopical observation of the presence of egg granu- lomas, and S. japonicum infection was detected simultaneously using liver tissue homogenate microscopy, examinations of mesenteric tissues for parasites, and modified Kato-Katz thick smear technique (Kato-Katz technique). A positive S. japonicum infection was defined as detection of S. japonicum eggs or adult worms by any of these methods. The rate of wild rodent capture and prevalence of S. japonicum infections in wild rodents were compared in different study villages and at different time periods, and the detection of S. japonicum infections in wild rodents was compared by different assays. Results The overall rate of wild ro- dent capture was 8.28% (237/2 861) in Dongzhi County, and the wild rodent capture rates were 9.24% (133/1 439) and 7.31% (104/1 422) in two study villages (χ² = 3.503, P = 0.061), and were 8.59% (121/1 409) and 7.99% (116/1 452) in June and September, 2021, respectively (χ² = 0.337, P = 0.561). The overall rate of wild rodent capture was 3.72% (77/2 072) in Duchang County, and the wild rodent capture rates were 6.91% (67/970) and 0.91% (10/1 102) in two study villages (χ² = 51.901, P < 0.001), and were 4.13% (39/945) and 3.37% (38/1 127) in June and September, 2021, respectively (χ² = 0.815, P = 0.365). Rattus norvegicus was the predominant rodent species captured in both counties, accounting for 70.04% (166/237) of all captured wild rodents in Dongzhi County and 88.31% (68/77) in Duchang County. No S. japonicum infection was detected in wild rodents captured in Duchang County. Nevertheless, the overall prevalence of S. japonicum infections was 51.05% (121/237) in wild rodents captured in Dongzhi County, with prevalence rates of 50.38% (67/133) and 51.92% (54/104) in two study villages (χ² = 0.098, P = 0.755), and 54.31% (63/116) and 47.93% (58/121) in September and June, 2021, respectively (χ² = 0.964, P = 0.326). Of 237 wild rodents captured in Dongzhi County, there were 140 (59.07%) rodents with visible hepatic egg granulomas, 117 (49.47%) tested positive for S. japonicum eggs by liver tissue homogenate microscopy, 34 (14.35%) tested positive for S. japonicum eggs with Kato-Katz technique; however, no adult S. japonicum worms were detected in mesenteric tissues. In addition, hepatic egg granulomas were found in all wild rodents tested positive for S. japonicum eggs with liver tissue homogenate microscopy. Conclusions The rate of wild rodent capture and prevalence of S. japonicum infection in wild rodents vary greatly in schistosomiasis-endemic areas of China, and the prevalence of S. japonicum infection is slightly higher in wild rodents captured in autumn than in summer. Liver tissue is recommended as the preferred sample for surveillance of S. japonicum infection in wild rodents, and a combination of macroscopical observation of hepatic egg granulomas and liver tissue homogenate microscopy may be a standard method for surveillance of S. japonicum infection in wild rodents.

Objective:To explore the relationship between the morphology of the carotid siphon, its related risk factors, and cerebral blood flow perfusion in patients with arteriosclerotic cerebral small vessel disease (aCSVD), and provide imaging evidence for the etiology of aCSVD.Methods:A total of 130 aCSVD patients hospitalized in the Department of Neurology of the First People′s Hospital of Hefei from March 2022 to June 2024, all of whom underwent multimodal imaging assessments, were enrolled. The baseline data were collected, and the morphology of the carotid siphon was visually evaluated using post-processing of head and neck computed tomography angiography (CTA), which was categorized into U-type ( n=63), C-type ( n=32), and V-type ( n=35). Calcification degree was semi-quantitatively assessed based on transverse CTA images. Cerebral perfusion was measured using magnetic resonance arterial spin labeling. The relationship between different siphon segment morphologies, calcification degrees, their risk factors, and cerebral blood flow perfusion was analyzed using analysis of variance and multinomial Logistic regression. Results:Univariate analysis of the 3 siphon types showed significant differences in low-density lipoprotein cholesterol [U-type (2.44±0.84) mmol/L,V-type (2.21±0.57) mmol/L, C-type (2.89±1.07) mmol/L, F=5.578, P=0.005], calcification degree [Among the 63 cases in the U-type group, 19 cases (30.15%) had mild calcification, 20 cases (31.75%) had moderate calcification, and 24 cases (38.10%) had severe calcification; among the 35 cases in the V-type group, 20 cases (57.14%) had mild calcification, 10 cases (28.57%) had moderate calcification, and 5 cases (14.29%) had severe calcification; among the 32 cases in the C-type group, 12 cases (37.50%) had mild calcification, 14 cases (43.75%) had moderate calcification, and 6 cases (18.75%) had severe calcification; χ2=13.092, P=0.011], and total aCSVD load [modified aCSVD load score: U-type 4.00(1.00, 4.00),V-type 3.00(1.00, 4.00),C-type 2.00(2.00, 4.00), H=9.997, P=0.007]. Multivariate Logistic regression revealed that patients with U-shaped siphons had a significantly higher overall aCSVD load than those with C-shaped siphons, with a regression coefficient of 0.728, and a statistically significant difference ( OR=2.070 ,95% CI 1.026-4.178, P=0.042). Additionally, total brain and white matter cerebral blood flow were decreased in patients with U-type siphons compared to those with C-type and V-type, primarily involving bilateral superior frontal gyri, left orbital frontal gyrus, and left straight gyrus regions (false discovery rate correction, P<0.05). Conclusions:The imaging manifestations of aCSVD are closely related to the shape of the internal carotid artery siphon.The U type siphon is more likely to lead to hemodynamic changes, resulting in decreased global and regional cerebral blood flow, and demonstrating a higher overall burden of aCSVD, which has certain clinical reference value for assessing the etiology of aCSVD.

Objective:To evaluate the clinical characteristics of Crohn's disease (CD) patients with secondary upper gastrointestinal fistulas and analyze risk factors for recurrence.Methods:A restrospective observational research method was performed. Clinical data of CD patients with secondary upper gastrointestinal fistulas treated at Eastern Theater General Hospital of PLA from January 2010 to August 2024 were analyzed. Based on postoperative recurrence of upper gastrointestinal fistulas, the patients were divided into recurrence group and non-recurrence group. Differences in clinical data between the two groups were compared, and further multivariate Logistic regression analysis was used to identify the risk factors for fistula recurrence.Results:A total of 72 CD patients with secondary upper gastrointestinal fistulas were included, consisting of 48 males and 24 females, with a mean age of 39±12 years and a disease duration of 97±56 months, accounting for 2.8% of all CD patients undergoing surgeries during the same period. Among these patients, 75 upper gastrointestinal fistulas from 72 patients were identified, including 67 patients of simple duodenal fistula, 2 of simple gastric fistula, and 3 of double fistulas (2 of double duodenal fistulas and 1 of duodenal fistula combined with gastric fistula) .The preoperative diagnostic positivity rates were 55.6% (40/72) for gastroscopy, 54.2% (39/72) for upper gastrointestinal contrast imaging, 22.2% (16/72) for abdominal CT, and 22.2% (16/72) for colonoscopy. A history of biologic therapy was present in 33.3% (24/72) of patients, but none achieved fistula healing. All 72 patients underwent surgical treatment, with primary lesion surgical approaches including resection with anastomosis (37 patients, 51.4%) and resection with stoma (35 patients, 48.6%). Except for one gastric fistula treated by resection, all other fistulas underwent primary repair. During a median follow-up of 69 (40, 113) months, 8 patients (11.1%) required reoperation due to recurrent upper gastrointestinal fistulas (classified as the recurrence group), while the remaining 64 patients were assigned to the non-recurrence group. Univariate analysis revealed that the recurrence group had a higher proportion of patients aged 30-40 years ( P = 0.003), malnutrition ( P = 0.040), and anastomosis near the duodenum ( P = 0.047), but a lower proportion of postoperative biologic use ( P = 0.007) .Multivariate Logistic regression analysis showed that malnutrition and anastomosis near the duodenum were not the risk factors for duodenal fistula recurrence (both P > 0.05) . Conclusions:Upper gastrointestinal fistulas secondary to CD are rare, predominantly presenting as simple duodenal fistulas. Diagnosis primarily relies on gastroscopy and gastrointestinal contrast imaging. Biologic therapy shows poor efficacy, and most patients do not recur after the primary repair surgery of duodenal fistulas.

Objective:To investigate the effects of Jianpi Rougan Xifeng Decoction on the behaviors and the Ca 2+ -CaM-CaMK Ⅱ signaling pathway in the striatum of rats with tic disorder models. Methods:Seventy-two SPF-grade SD male rats were randomly divided into blank group, model group, tiapride group (15.93 mg/kg, intragastric administration), low-dose (4.32 g/kg, intragastric administration), medium-dose (8.64 g/kg, intragastric administration) and high-dose (17.28 g/kg, intragastric administration) Jianpi Rougan Xifeng Decoction groups, with 12 rats in each group. Rats in the blank group and model group were gavaged with 0.5 mg/kg of distilled water while rats in other 4 groups were gavaged with corresponding drugs, all rats were gavaged once a day for 28 days.The evaluations of motor behavior and stereotyped behavior were conducted using the Kadasah scoring method and the Diamond scoring method. Calcium content in the striatum was detected using a calcium assay kit. Immunohistochemical analysis was employed to detect the expression of dopamine transporter (DAT) and inositol 1, 4, 5-triphosphate (IP3) in the striatum of rats. Western blot was used to assess the expression of calmodulin (CaM) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the striatum. RT-PCR was utilized to detect the expression of CaM and CaMK Ⅱ mRNA in the striatum. All data were processed using SPSS 26.0 software, and comparisons among multiple groups were performed using one-way ANOVA and Kruskal-Wallis test.Results:(1) After four weeks of pharmacological intervention, statistically significant differences were observed in the locomotor activity scores and stereotyped scores among the six groups of rats ( H=41.20, 44.24, both P<0.01). Specifically, the locomotor activity scores(3.00(3.00, 3.25), 1.00(0.75, 1.25), 1.00(0.75, 2.00), 1.00(0, 1.00)) and stereotyped scores(3.00(3.00, 4.00), 1.00(0.75, 2.00), 2.00(0.75, 2.00), 1.00(0, 1.25)) in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups were significantly lower than those in the model group (all P<0.01). (2) Results from the calcium assay kit revealed statistically significant differences in striatal calcium content among the six groups of rats ( F=146.67, P<0.01). The calcium content in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups was significantly lower than that in the model group (all P<0.01). Additionally, the calcium content in the medium-dose ((0.40±0.02)mmol/g) and high-dose ((0.30±0.03)mmol/g) Jianpi Rougan Xifeng Decoction groups was lower than that in the low-dose group ((0.48±0.02)mmol/g) (both P<0.01). (3) Immunohistochemical results showed that there were statistically significant differences in the mean optical density values of DAT and IP3 in the striatum among the six groups of rats ( F=25.57, 154.98, both P<0.01). The IP3 mean optical density in the tiapride group and the Jianpi Rougan Xifeng Decoction groups with medium and high doses exhibited lower values compared to the model group (all P<0.05), whereas the DAT mean optical density displayed higher values in these groups compared to the model group (all P<0.05). The low-dose Jianpi Rougan Xifeng Decoction group also exhibited a lower optical density value of IP3 compared to the model group( P<0.05). The optical density values of IP3 (2.68±0.21, 2.40±0.22) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than that in the low-dose group (4.27±0.23) (both P<0.01). (4) Western blot results indicated that there were statistically significant differences in the protein expression levels of CaM and CaMK Ⅱ in the striatum among the six groups of rats ( F=233.03, 118.60, both P<0.01). The protein expression levels of CaM and CaMK Ⅱ in the tiapride group and the low-dose, medium-dose, and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the model group (all P<0.01). The protein expression levels of CaM (1.02±0.06, 0.84±0.02) and CaMK Ⅱ (0.48±0.03, 0.40±0.02) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the low-dose group (1.21±0.03, 0.57±0.02)) (all P<0.05). Additionally, the protein expression level of CaM in the high-dose Jianpi Rougan Xifeng Decoction group was lower than that in the medium-dose group( P<0.05).(5) The RT-PCR results indicated significant variations in the mRNA expression levels of CaM and CaMK Ⅱ within the striatum across the six groups rats ( F=30.54, 20.78, both P<0.01). The mRNA expression levels of CaM and CaMK Ⅱ in the tiapride group and the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the model group (both P<0.05). The mRNA expression levels of CaMK Ⅱ (1.38±0.17) in the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the low-dose group (1.99±0.27) ( P<0.01). Conclusion:Jianpi Rougan Xifeng Decoction can improve locomotor activity and stereotyped behavior in rats with tic disorder model. The mechanism may be through inhibiting the Ca 2+ -CaM-CaMK Ⅱ signaling pathway and regulating the expression of DAT and IP3, thereby modulating the release and recovery of dopamine and reducing the occurrence of tic symptoms.

Objective To explore the evaluation value of thyroid function indicators[thyroid stimulating hormone(TSH),free thyroxine(FT4),free triiodothyronine(FT3)]combined with transcranial Doppler ultrasound(TCD)and carotid ultrasound in the assessment of vascular stenosis in atherosclerotic cerebral infarction(ASCI),providing a reference for clinical targeted treatment.Methods A total of 182 patients with ASCI admitted to Handan Frist Hospital from October 2021 to September 2023 were selected and all of them underwent TCD,carotid artery ultrasound and thyroid function examination.Digital subtraction angiography was used as the gold standard to analyze the evaluation effect of TCD and carotid artery ultrasound combined with TSH,FT4 and FT3 in vascular stenosis of ASCI.Results Among the 182 patients with ASCI,DSA confirmed 64 cases(35.16％)with mild internal carotid artery stenosis,69 cases(37.91％)with moderate stenosis,29 cases(15.93％)with severe stenosis,and 20 cases(10.99％)with complete occlusion.There was no statistically significant difference in clinical data among groups with different degrees of vascular stenosis(P＞0.05).The peak systolic velocity(PSV)and end-diastolic volume(EDV)of the internal carotid artery in different groups with different degrees of vascular stenosis showed an increasing trend with the severity of vascular stenosis,while the pulse index(PI),resistance index(RI),and diameter(D)showed a decreasing trend(P＜0.05).In different groups with different degrees of vascular stenosis,TSH and FT4 levels increased with the severity of stenosis,while FT3 levels decreased(P＜0.05).TSH and FT4 were positively correlated with the degree of vascular stenosis,while FT3 was negatively correlated(P＜0.05).TSH and FT4 were positively correlated with PSV and EDV,and negatively correlated with RI,PI,and D.FT3 was positively correlated with RI,PI,and D,and negatively correlated with PSV and EDV(P＜0.05).The combined evaluation of RI,PI,D,PSV,EDV,TSH,FT4,and FT3 yielded the highest area under the curve(AUC)value of 0.941 for assessing ASCI vascular stenosis(P＜0.05).Conclusion The combination of TCD,carotid ultrasound,and thyroid function tests have high value in the assessment of ASCI vascular stenosis.The joint evaluation of RI,PI,D,PSV,EDV,TSH,FT4 and FT3 is beneficial for diagnosing different degrees of vascular stenosis,providing a reference for clinical treatment.r clinical treatment.

Objective: To explore the brain-predicted age difference (Brain-PAD) in patients with type 2 diabetes mellitus (T2DM) by a machine learning prediction model based on structural magnetic resonance ( sMRI) in the Southwest University Adult Lifespan Dataset (SALD) , and to reveal the relationship between Brain-PAD and dura- tion of T2DM and cognition . Methods: Group comparisons about demographic variables and cognitive function were conducted respectively in local database of 104 T2DM patients and 83 healthy controls (HC) . The prediction model via Gaussian process regression (GPR) was constructed by training sMRI data of 329 healthy volunteers in SALD , then its performance was validated and evaluated . Furthermore , Brain-PAD ( predicted age-chronological age) in the local database was calculated . Group comparisons of Brain-PAD between T2DM patients and HCs were conducted by Mann-Whitney U test. Finally , Pearson correlation coefficient (r) was calculated between Brain-PAD and duration of disease and cognition . Results: Poor performance in auditory verbal learning test (AVLT)-delayed recall , AVLT-recognition , symbol digital modalities test (SDMT) (P < 0. 05) , and increased Brain-PAD were ob- served in T2DM patients , compared with HCs [1 . 619 ( - 4. 001 , 8. 272) years vs - 1 . 289 ( - 4. 128 , 4. 134) years , Z = 2. 056 , P = 0. 034] . Notably , the median of Brain-PAD in T2DM group was positive , indicating that the brain of T2DM patient maybe relatively “older”than his chronological age . Brain-PAD in T2DM group was as- sociated with performance in AVLT-immediate recall ( r = 0. 291 , P = 0. 003) , AVLT-delayed recall ( r = 0. 248 , P = 0. 011) , SDMT( r = 0. 376 , P = 0. 001) and trail making test (TMT)-A ( r = - 0. 206 , P = 0. 036) . However , the relationships between Brain-PAD and duration of T2DM were not explored . Conclusion Decreased cognitive function in patients with T2DM is demonstrated in this study . The machine learning prediction model based on sMRI supports the identification of brain aging objectively in patients with T2DM .

Objective To develop an assessment scale for post-intensive care syndrome in pediatrics(PICS-p)and evaluate its reliability and validity,aiming to provide a scientifically sound and feasible tool for clinical assessment.Methods Based on the PICS-p conceptual framework,combined with literature review,semi-structured interviews,and Delphi expert consultation,a preliminary scale was developed.From June to December 2023,a survey was conducted among 330 pediatric patients who were discharged from a tertiary children's hospital in Hangzhou,followed by a two-week retest with 30 children to assess the reliability and validity of the scale.Results Finally 304 children completed the survey.The Post-Intensive Care Syndrome Scale for Children consists of 4 dimensions of physical dysfunction,cognitive dysfunction,psychological dysfunction and social dysfunction,with a total of 29 entries,with a cumulative variance contribution of 61.705％.The content validity index for individual items ranged from 0.800 to 1.000,and the content validity index for the scale as a whole was 0.98.The dimensions of the scale showed positive correlations with the Functional Status Scale(r=0.438-0.581,P＜0.001).The overall Cronbach's α coefficient of the scale was 0.847;the split-half reliability was 0.868;the test-retest reliability was 0.832.Conclusion The scale demonstrates good reliability and validity,and it is suitable for assessing the severity of PICS-p in pediatric patients discharged from the PICU.