Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Objective To explore the relevant risk factors of H.pylori infection,and provide reference for prevention and treatment of H.pylori in this area,and further provide theoretical basis for the prevention and treatment of gastric cancer.Methods A total of 1200 residents in four districts of Haikou city were investigated by questionnaire and urea 14 C breath test by holistic stratified random sampling to calculate the population infection rate and analyze the risk factors of infection.Results The total infection rate was 32.5％,which was lower than the national H.pylori infection rate.No consumption of fruits and vegetables,no habit of washing hands before meals,and people with gastrointestinal symptoms,are independent risk factors of H.pylori infection.No consumption of pickled products is of great significance to prevent H.pylori infection.Conclusion The prevalence of H.pylori infection in the population of Haikou is lower than the national average,and H.pylori infection is closely related to the poor living habits of residents.

Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5％)cases of male and 20(43.5％)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4％)of GCB subtype,32 cases(69.6％)of non-GCB subtype.32 cases(69.6％)of Ki-67 ≥80％.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9％,complete response(CR)rate was 47.2％,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6％and 84.9％,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2％and 68.9％,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5％and 52.9％(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.

Objective: To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). Materials and Methods: We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slope max) and model-based (Ktrans , Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Results: Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans -10th and Ktrans -mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans -mean and Ktrans -max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans -mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). Conclusion DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and K trans -mean could be promising biomarkers for determining the response to GCs.