ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

ObjectiveTo investigate the status and influencing factors of latent tuberculosis infection (LTBI) among close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, and to provide scientific evidence for the development of tuberculosis infection testing and preventive intervention strategies for close contacts of bacteriologically positive patients. MethodsFrom October 2022 to October 2023, patients with bacteriological confirmed pulmonary tuberculosis registered in Jing’an District, Shanghai, and their close contacts were enrolled as the research subjects. The close contacts were screened for tuberculosis infection using the interferon-γ release assay (IGRA). The chi-square test and binary logistic regression model were used to analyze factors influencing LTBI. ResultsA total of 112 close contacts were included, of whom 30 (26.79%) were male and 82 (73.21%) were female. The age ranged from 1 to 86 years, with a median (25th, 75th percentiles) of 47.50 (32.25, 61.00) years. The infection rate of LTBI was 21.43% (24/112), and the incidence of active pulmonary tuberculosis was 2.68% (3/112). Univariate analyses showed that a positive sputum smear of the index case, being a direct relative of the index case, co-living, and not wearing a mask were significantly associated with LTBI (all P<0.05). Multivariate logistic regression analyses showed that the risk of latent infection in close contacts of the index case with a positive sputum smear was 6.50 times higher than in those with a negative sputum smear (95%CI: 1.82‒23.25, P=0.004). ConclusionThe infection rate of LTBI in close contacts of patients with bacteriologically confirmed pulmonary tuberculosis in Jing’an District, Shanghai, is relatively high, and close contacts of sputum smear-positive patients face an even higher risk of infection. Therefore, tuberculosis infection screening and follow-up management should be strengthened for this population.

ObjectiveTo analyze the reported incidence rate of pulmonary tuberculosis and diagnosis and treatment of pulmonary tuberculosis patients in Jing’an District, Shanghai from 2018 to 2023, and to provide a reference basis for the prevention and treatment of pulmonary tuberculosis. MethodsMedical records, including demographic information, diagnosis and treatment information, laboratory testing results, treatment outcomes, patient prognoses, and etc., of all the patients registered for first-time management, with the disease type of pulmonary tuberculosis in Jing’an District from January 1, 2018 to December 31, 2023 were extracted from the Tuberculosis Management Information System of China’s Disease Control and Prevention Information System.The reported incidence rate of pulmonary tuberculosis from 2018 to 2023 was analyzed. Additionally, the delay rate for medical consultation, diagnostic delay rate, prevalence of pulmonary cavity, rate of sputum smear-positive, sputum conversion rate of smear-positive patients after 2 months, proportion of deaths attributable to pulmonary tuberculosis or other causes, and the proportion of patients with treatment duration >1 year in 2018‒2019, 2020‒2022, and 2023 were compared, respectively. ResultsA total of 1 378 pulmonary tuberculosis patients were registered for management in Jing’an District in 2018‒2023, with a reported incidence rate of 25.97/100 000, 25.72/100 000, 23.93/100 000, 22.36/100 000, 18.18/100 000, and 22.32/100 000, respectively. Meanwhile, the overall reported incidence rates in 2018‒2019, 2020‒2022, and 2023 were 25.84/100 000, 21.53/100 000, and 22.32/100 000, respectively. The median age of the patients was 56 (33, 67) years, with a male-to-female ratio of 1.94∶1. The patients with a household registration of Shanghai accounted for 70.75%, among whom those aged between 61‒<71 years were the majority. Whereas, those aged between 31‒<41 years accounted for a higher proportion in the long-term resident population. The median delay times of patient’s medical consultation, diagnosis, and case-finding were 25 (19, 33) days, 29 (21, 43) days, and 41 (32, 66) days, respectively. The delay rate for medical consultation was higher in 2020‒2022 (47.99%) and 2023 (46.89%), but lower in 2018‒2019 (31.02%). In 2018‒2019, 2020‒2022, and 2023, the diagnostic delay rate was 12.41% (68/548), 13.53% (84/621), and 16.75% (35/209), respectively. Besides, during the same time the delay rate in case-finding was 19.53%, 27.05% and 34.45%, respectively, all exhibited an increasing trend. Furthermore, the rate of patients with pulmonary cavity was 16.06%, 14.98%, and 11.00%, respectively, showing a decreasing trend. Furthermore, the rate of sputum smear-positive was 27.19%, 33.33% and 32.54%, while the sputum conversion rate of smear-positive patients after 2 months was 81.21%, 85.02% and 89.71%. The mortality rates due to tuberculosis and other causes were 3.10%, 5.64%, and 3.83%, respectively. The proportion of patients with a treatment duration of ≥365 days was 44.27% in 2018‒2019, 39.93% in 2020‒2022 and 26.60% in 2023. ConclusionThe overall reported incidence rate of pulmonary tuberculosis in Jing’an District showed a decline trend from 2018‒2022, with a slight rebound in 2023. Targeted interventions should be prioritized for the elderly with local household registration and young permanent residents without Shanghai household registration.

Objective:To investigate the influencing factors of enlarged perivascular space (PVS) in relapsing-remitting multiple sclerosis (RRMS) patients and their relationship with cognitive function.Methods:Twenty-seven individuals with RRMS (RRMS group) and 27 healthy controls (healthy control group) who presented to the Department of Neurology, the Sixth Medical Center of People′s Liberation Army General Hospital from July 2022 to November 2024 underwent cognitive function assessments. PVS volume fractions, lesion volumes, and brain volumes were calculated using FreeSurfer, FSL, and other relevant softwares. Group differences in PVS volume fractions, lesion volumes, brain volumes, and cognitive function assessments were compared. Furthermore, correlations between PVS volume fractions and lesion volumes, brain volumes, and cognitive function assessments were analyzed within the RRMS group.Results:Compared with the healthy control group, the RRMS group exhibited significantly higher PVS volume fractions in white matter (PVS_w) (3.14‰±0.29‰ vs 2.91‰±0.30‰, t=2.877, P=0.006) and PVS volume fractions in deep gray matter (PVS_d) (2.25‰±0.10‰ vs 2.17‰±0.09‰, t=2.681, P=0.010), indicating an enlargement of the PVS. Compared with the healthy control group, the RRMS group showed a significant decrease in both white matter volumes [297.3 (274.3, 340.2) ml vs (324.2 (311.0, 350.0) ml, U=-2.085, P=0.037] and deep grey matter volumes [40.2 (34.9, 43.6) ml vs 42.7 (40.2, 44.8) ml, U=-2.292, P=0.022]. Compared with the healthy control group, the RRMS group showed significantly lower scores in cognitive function assessments ( P<0.05). Univariate analysis showed that PVS_w in the RRMS group was significantly positively correlated with age ( r=0.486), white matter lesion volumes ( r=0.437) and deep gray matter lesion volumes ( r=0.394;all P<0.05); PVS_d was also significantly positively correlated with white matter lesion volumes ( r=0.418) and deep gray matter lesion volumes ( r=0.480; both P<0.05). Multiple linear regression analysis showed that age ( B=0.011,95% CI 0.004-0.017), white matter lesion volumes ( B=0.026,95% CI 0.011-0.040) and deep gray matter lesion volumes ( B=0.401,95% CI 0.032-0.771) in the RRMS group were significantly positively correlated with PVS_w, while white matter lesion volumes ( B=0.007,95% CI 0.001-0.014) and deep gray matter lesion volumes ( B=0.204,95% CI 0.029-0.380) were significantly positively correlated with PVS_d (both P<0.05). Univariate analysis showed that immediate memory score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.428), and was significantly positively correlated with education level ( r=0.471), deep gray matter volumes ( r=0.530) and total brain volumes ( r=0.389; all P<0.05); short-term delayed memory score in the RRMS group was significantly negatively correlated with age ( r=-0.390), PVS_w ( r=-0.417) and white matter lesion volumes ( r=-0.438), and was significantly positively correlated with gender ( r=0.393), white matter volumes ( r=0.478), deep gray matter volumes ( r=0.579) and total brain volumes ( r=0.602;all P<0.05); verbal fluency test score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.409) and was significantly positively correlated with education level ( r=0.419) and total brain volumes ( r=0.400;all P<0.05). Multiple linear regression analysis revealed that PVS_d ( B=-5.572, 95% CI -11.513--0.368) and brain volumes ( B=0.012, 95% CI 0.001-0.023) in the RRMS group were both significant predictors of immediate recall score, while PVS_d ( B=-14.203,95% CI -27.514--0.891) was an independent predictor of verbal fluency test score (all P<0.05). Conclusions:The PVS is enlarged in individuals with RRMS compared with the healthy controls, and increased lesion volumes may be a significant predictor. Furthermore, enlarged PVS in the deep gray matter may be a significant predictor of impairment of verbal memory and verbal function in individuals with RRMS.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

Based on the national policy direction of improving the individual account crediting method for employees'basic medical insurance,it designed three individual account reform scenarios,considering the individual account reform and fund sustainability considerations.Based on the 2022 data of the basic medical insurance for employees in Shandong Province,simulations were conducted to predict the overall scale of individual account reform funds released and individual subtractions under each scenario after the full implementation of the individual account reform in 2024,as well as to conduct an early warning analysis of public opinion risks for key populations.The results indicated that Plan I had the largest total amount of released funds from individual accounts(16.55 billion yuan),but the highest per capita monthly reduction in credits(52.97 yuan),thereby increasing the risk of generating social public sentiment.Plan III minimized the resistance to the implementation of the individual account reform but has the smallest total amount of released funds from individual accounts(13.484 billion yuan).Plan II achieved areas such as the provincial government and oil fields have the highest public sentiment risk due to the highest reduction ratio for retirees(>90%);11 coordinated areas have a percentage of retiree subtraction of more than 80%.It provided empirical evidence for policymakers on different plans for the reform of individual accounts in the employee basic medical insurance and their impacts,and suggested that high-risk areas should be given special attention,adopting refined and differentiated policy measures to effectively alleviate social public sentiment pressure and ensure the smooth progress of the reform.

Based on the national policy direction of improving the individual account crediting method for employees'basic medical insurance,it designed three individual account reform scenarios,considering the individual account reform and fund sustainability considerations.Based on the 2022 data of the basic medical insurance for employees in Shandong Province,simulations were conducted to predict the overall scale of individual account reform funds released and individual subtractions under each scenario after the full implementation of the individual account reform in 2024,as well as to conduct an early warning analysis of public opinion risks for key populations.The results indicated that Plan I had the largest total amount of released funds from individual accounts(16.55 billion yuan),but the highest per capita monthly reduction in credits(52.97 yuan),thereby increasing the risk of generating social public sentiment.Plan III minimized the resistance to the implementation of the individual account reform but has the smallest total amount of released funds from individual accounts(13.484 billion yuan).Plan II achieved areas such as the provincial government and oil fields have the highest public sentiment risk due to the highest reduction ratio for retirees(>90%);11 coordinated areas have a percentage of retiree subtraction of more than 80%.It provided empirical evidence for policymakers on different plans for the reform of individual accounts in the employee basic medical insurance and their impacts,and suggested that high-risk areas should be given special attention,adopting refined and differentiated policy measures to effectively alleviate social public sentiment pressure and ensure the smooth progress of the reform.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

Objective:To investigate the influencing factors of enlarged perivascular space (PVS) in relapsing-remitting multiple sclerosis (RRMS) patients and their relationship with cognitive function.Methods:Twenty-seven individuals with RRMS (RRMS group) and 27 healthy controls (healthy control group) who presented to the Department of Neurology, the Sixth Medical Center of People′s Liberation Army General Hospital from July 2022 to November 2024 underwent cognitive function assessments. PVS volume fractions, lesion volumes, and brain volumes were calculated using FreeSurfer, FSL, and other relevant softwares. Group differences in PVS volume fractions, lesion volumes, brain volumes, and cognitive function assessments were compared. Furthermore, correlations between PVS volume fractions and lesion volumes, brain volumes, and cognitive function assessments were analyzed within the RRMS group.Results:Compared with the healthy control group, the RRMS group exhibited significantly higher PVS volume fractions in white matter (PVS_w) (3.14‰±0.29‰ vs 2.91‰±0.30‰, t=2.877, P=0.006) and PVS volume fractions in deep gray matter (PVS_d) (2.25‰±0.10‰ vs 2.17‰±0.09‰, t=2.681, P=0.010), indicating an enlargement of the PVS. Compared with the healthy control group, the RRMS group showed a significant decrease in both white matter volumes [297.3 (274.3, 340.2) ml vs (324.2 (311.0, 350.0) ml, U=-2.085, P=0.037] and deep grey matter volumes [40.2 (34.9, 43.6) ml vs 42.7 (40.2, 44.8) ml, U=-2.292, P=0.022]. Compared with the healthy control group, the RRMS group showed significantly lower scores in cognitive function assessments ( P<0.05). Univariate analysis showed that PVS_w in the RRMS group was significantly positively correlated with age ( r=0.486), white matter lesion volumes ( r=0.437) and deep gray matter lesion volumes ( r=0.394;all P<0.05); PVS_d was also significantly positively correlated with white matter lesion volumes ( r=0.418) and deep gray matter lesion volumes ( r=0.480; both P<0.05). Multiple linear regression analysis showed that age ( B=0.011,95% CI 0.004-0.017), white matter lesion volumes ( B=0.026,95% CI 0.011-0.040) and deep gray matter lesion volumes ( B=0.401,95% CI 0.032-0.771) in the RRMS group were significantly positively correlated with PVS_w, while white matter lesion volumes ( B=0.007,95% CI 0.001-0.014) and deep gray matter lesion volumes ( B=0.204,95% CI 0.029-0.380) were significantly positively correlated with PVS_d (both P<0.05). Univariate analysis showed that immediate memory score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.428), and was significantly positively correlated with education level ( r=0.471), deep gray matter volumes ( r=0.530) and total brain volumes ( r=0.389; all P<0.05); short-term delayed memory score in the RRMS group was significantly negatively correlated with age ( r=-0.390), PVS_w ( r=-0.417) and white matter lesion volumes ( r=-0.438), and was significantly positively correlated with gender ( r=0.393), white matter volumes ( r=0.478), deep gray matter volumes ( r=0.579) and total brain volumes ( r=0.602;all P<0.05); verbal fluency test score in the RRMS group was significantly negatively correlated with PVS_d ( r=-0.409) and was significantly positively correlated with education level ( r=0.419) and total brain volumes ( r=0.400;all P<0.05). Multiple linear regression analysis revealed that PVS_d ( B=-5.572, 95% CI -11.513--0.368) and brain volumes ( B=0.012, 95% CI 0.001-0.023) in the RRMS group were both significant predictors of immediate recall score, while PVS_d ( B=-14.203,95% CI -27.514--0.891) was an independent predictor of verbal fluency test score (all P<0.05). Conclusions:The PVS is enlarged in individuals with RRMS compared with the healthy controls, and increased lesion volumes may be a significant predictor. Furthermore, enlarged PVS in the deep gray matter may be a significant predictor of impairment of verbal memory and verbal function in individuals with RRMS.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.