ObjectiveTo explore the potential mechanisms of Leigongteng （Tripterygium wilfordii Hook. f.） in treating rheumatoid arthritis （RA） using bioinformatics analysis and experimental validation. MethodsBioinformatics approaches， including the Gene Expression Omnibus （GEO）， the traditional Chinese medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Gene Ontology （GO） enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， protein-protein interaction （PPI） network analysis， molecular docking， receiver operating characteristic （ROC） analysis， and immune infiltration analysis， were used to predict the key active components of Leigongteng and its target genes for RA treatment. Experimental validation was conducted using human rheumatoid arthritis fibroblast-like synoviocytes （HFLS-RA） in vitro， with methotrexate as the positive control. A scratch assay was performed to assess cell migration after 24 hours of culture. Western blotting was used to detect protein expression levels， qPCR was used to measure target gene mRNA levels， and ELISA was conducted to evaluate inflammatory cytokine levels， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α）. ResultsA total of 117 target genes of Leigongteng were identified and intersected with RA-related genes， yielding 55 key genes. Further screening identified three core genes： PTGS2， CXCR4， and TIMP1. Based on the correspondence between potential drug targets and key components， triptolide and nobiletin were identified as the primary active compounds. Molecular docking results showed that both triptolide and nobiletin had binding energies lower than -5 kcal/mol with their respective target proteins， indicating strong interactions. In vitro experiments demonstrated that， compared with the blank control group， the triptolide， nobiletin， and positive control groups exhibited reduced cell migration rates after 24 hours of culture （P＜0.01）. The expression levels of PTGS2 and CXCR4 （both mRNA and protein） were significantly downregulated， while TIMP1 expression was upregulated. Levels of IL-1β， IL-6， and TNF-α decreased， whereas IL-10 levels increased （P＜0.01）. Compared with the positive control group， the triptolide and nobiletin groups showed increased cell migration rates， upregulated PTGS2 and CXCR4 expression （mRNA and protein）， downregulated TIMP1 expression （mRNA and protein）， increased IL-1β， IL-6， and TNF-α levels， and decreased IL-10 levels （P＜0.05 or P＜0.01）. ConclusionThe key active components of Leigongteng， triptolide and nobiletin， may alleviate RA by inhibiting PTGS2 and CXCR4 while promoting TIMP1 expression， thereby suppressing inflammatory responses.

OBJECTIVE To provide a reference for pharmaceutical care in patients with ulcerative colitis （UC） and ankylosing spondylitis （AS） who developed pustular psoriasis induced by infliximab. METHODS Clinical pharmacists participated in the pharmaceutical care process of a patient with UC and AS who developed pustular psoriasis after using infliximab. The clinical pharmacists determined， using Naranjo’s Scale， that the correlation between the patient’s pustular psoriasis and infliximab was “likely”. Regarding the patient’s development of pustular psoriasis after using infliximab， the clinical pharmacists recommended discontinuing infliximab and switching to Upadacitinib extended-release tablets. For the patient’s skin allergic reaction after using upadacitinib， the clinical pharmacists advised continuing the use of upadacitinib and closely monitoring any potential adverse reactions during the treatment period. RESULTS The clinicians adopted the clinical pharmacists’ recommendation. Following the treatment， the patient’s symptoms were significantly alleviated， and the patient was discharged with medication. The follow-up after discharge showed that the treatment was effective and well-tolerated. CONCLUSIONS The clinical pharmacists analyzed the causal relationship between infliximab and pustular psoriasis. Through pharmaceutical care measures such as dynamic monitoring of skin lesions， evaluation of treatment responses， and optimization of drug regimens， they assisted the physicians in formulating an individualized medication plan， ensuring the safety and efficacy of the patient’s medication use.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

OBJECTIVES: To evaluate the strategies and outcomes of assisted reproductive technology (ART) for fertility preservation and promotion in women with malignant tumors, and to analyze ART outcomes across different tumor types. METHODS: We conducted a retrospective analysis of female patients who underwent ART for fertility preservation or treatment at the Reproductive Center of the Women's Hospital, Zhejiang University School of Medicine, between January 1, 2018, and December 31, 2023. A total of 163 ART-aided pregnancy patients with malignant tumors were included in the case group, among which 6 patients underwent embryo cryopreservation for fertility preservation before radiotherapy or chemotherapy. Additionally, 11 unmarried women underwent oocyte cryopreservation due to borderline ovarian tumors, ovarian cancer, breast cancer, or hematological malignancies. The control group was selected from women without a history of malignant tumors who received ART treatment during the same period, using propensity score matching at a ratio of 1∶2, resulting in 326 cases. Data were collected through the reproductive medical record system and telephone follow-up (as of October 31, 2024). Baseline characteristics, controlled ovarian hyperstimulation parameters, laboratory indicators, and pregnancy outcomes were compared between case and control groups and among patients with different tumor types, and the tumor recurrence of the patients was followed up. RESULTS: Patients in the case group had significantly lower ovarian reserve (AMH, AFC) and a higher proportion of diminished ovarian reserve compared to the control group (all P<0.01). Regarding the ovulation induction protocol, the proportion of patients using the minimal stimulation protocol in the case group was significantly higher than that in the control group (29.45% vs. 12.88%, P<0.01), and the total dosage of gonadotropins used was lower (P<0.01). In terms of assisted reproductive outcomes, there were no statistically significant differences between the two groups in the number of retrieved oocytes, number of high-quality embryos, fertilization rate, cumulative pregnancy rate, cumulative live birth rate, or miscarriage rate (all P>0.05). However, the number of oocyte retrieval cycles and embryo transfer cycles required to achieve a live birth outcome in the case group were significantly higher than those in the control group (both P<0.05). Subgroup analysis showed that there were no significant differences in cumulative pregnancy rate and live birth rate among patients with different tumor types (thyroid cancer, reproductive system tumors, breast cancer, lung cancer). Nevertheless, lung cancer patients had the lowest ovarian reserve and required the most oocyte retrieval cycles due to their older age; breast cancer patients had a relatively lower fertilization rate partially because some of them were complicated with male factors. A follow-up of 154 tumor patients (with a follow-up rate of 88.5%) revealed that 6 patients (4.20%) had tumor recurrence, and 1 breast cancer patient died due to tumor recurrence. None of the 11 unmarried patients who had undergone oocyte cryopreservation had used the cryopreserved oocytes for assisted pregnancy yet, and 1 patient who had undergone fertility preservation died due to tumor recurrence. CONCLUSIONS Women of reproductive age with malignant tumors are at risk of diminished fertility. ART can effectively preserve and promote fertility, enabling favorable pregnancy and live birth outcomes. It is recommended to initiate a multidisciplinary assessment promptly prior to radiotherapy/chemotherapy and formulate an individualized ART regimen for fertility preservation or promotion, so as to achieve reproductive goals or safeguard future fertility potential.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

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

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Objective To investigate the causal relationship between rheumatoid arthritis (RA) and pulmonary hypertension (PH) by the Mendelian randomization design method.Methods The data on single nucleotide polymorphisms (SNPs) of exposure and outcome were obtained by using publicly available ge-nome-wide association studies and the summary analysis was conducted;the inverse variance-weighted (IVW) method as the primary analysis method was used to assess the causal effect of exposure factors (RA) on the outcomes (PH);the MR-Egger regression method,weighted median method (WM),weighted model and sim-ple model were used as supplementary regression explanations to conduct the sensitivity analysis for evalua-ting the robustness of results;the "heterogeneity" function was used to calculate the "P value" for testing the heterogeneity,and the "horizontal pleiotropy" function was used to calculate the "P value" to test the level pleiotropy.Results In the "FINNGEN data" included in the GWAS database,the SNPs had the strong corre-lation after removing the linkage imbalance by Mendelian random analysis and satisfying "P<5×10-8" were selected,the effective instrumental variables were obtained by integrating the exposure and outcome.The IVW results showed that RA was a risk factor for PH (OR=1.295,95％CI:1.053-1.593,P=0.014)."heteroge-neity" function test showed that the results had no heterogeneity (P=0.221);" horizontal pleiotropy" func-tion test showed that the results had no horizontal pleiotropy (P=0.877),and the total results were steady and reliable.Conclusion RA is a risk factor for PH,and RA is positively associated with PH.

Objective To explore the clinical characteristics and risk factors of death during hospitalization in patients with community-acquired pneumonia(CAP)complicated with diabetes mellitus(DM).Methods A retrospective analysis was performed on 566 patients with CAP hospitalized in the Second Affiliated Hospital of Kunming Medical University from January 2018 to January 2022.The patients were divided into simple CAP group(n=478)and CAP combined with diabetes(CAP+DM)group(n=88)according to whether they had diabetes,and then CAP+DM group(n=88)was divided into survival group(n=69)and death group(n =19)according to whether the patients died during hospitalization.The clinical data and laboratory test indicators of patients in different groups were compared.Cox regression analysis was used to screen the risk factors of death during hospitalization in the CAP+DM group.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of independent risk factors on hospitalization death.Results Compared with the simple CAP group,the CAP+DM group had significant differences in age,concomitant hypertension,coronary heart disease,CURB-65 score,neutrophil to lymphocyte ratio(NLR),C-reactive protein(CRP),procalcitonin(PCT),albumin(ALB),prealbumin(PA),glucose(GLU),serum potassium(K),calcium(Ca),phosphorus(P),magnesium(Mg),lactic acid(Lac),non-invasive ventilation time,ICU occupancy rate and mortality rate(P<0.05);Compared with the survival group,there were statistically significant differences in CURB-65 score,NLR,CRP,PCT,GIU,ALB,PA,serum iron(Fe),Ca,non-invasive ventilation time,and ICU admission rate among the death group patients(P<0.05).Cox regression analysis showed that the increase of NLR level and the decrease in PA level were the risk factors for in-hospital death in patients with CAP complicated with diabetes(P<0.05).When the PA cutoff value was 91 mg/L,the AUC,sensitivity,and specificity for predicting in-hospital death of CAP patients with diabetes were 0.849,84.2%and 81.2%,respectively.Conclusion Patients with CAP combined with diabetes are more serious and have worse prognosis than those with CAP alone.PA has a good predictive value for the prognosis of these patients.Early detection and active intervention should be carried out to reduce the in-hospital mortality of patients.

Objective:To investigate the control situation of drinking water-type endemic fluorosis (hereinafter referred to as drinking water fluorosis) in Xinjiang Production and Construction Corps (hereinafter referred to as the Corps), identify weak links in prevention and control, and provide reference for precise prevention and control of drinking water fluorosis in the Corps.Methods:Monitoring data of drinking water fluorosis areas in the Corps from January to December 2022 were collected from the Corps Center for Disease Control and Prevention, the level of fluoride in drinking water and the prevalence of dental fluorosis in children aged 8 - 12 were analyzed retrospectively.Results:In 2022, the qualified rate of water fluoride in the disease affected TuanChang of the Corps was 100.00% (62/62), and the qualified rate of water fluoride in the disease affected company was 99.44% (705/709). The prevalence of dental fluorosis in children aged 8 - 12 in the disease affected TuanChang was 3.38% (1 412/41 714), and there was no statistically significant difference in the prevalence of dental fluorosis among different age groups (χ 2 = 6.07, P = 0.194). The prevalence of dental fluorosis in children aged 8 - 12 in the TuanChang where the company with water fluoride exceeding standard was located (6.00%, 106/1 768) was higher than that in the TuanChang where the company with qualified water fluoride was located (3.27%, 1 306/39 946, χ 2 = 38.47, P < 0.001). Conclusion:In 2022, the drinking water fluorosis in the Corps has reached the control standard, but attention still should be paid to the water improvement situation and maintenance of water improvement projects in some water fluoride exceeding standard companies, in order to prevent sustained dental fluorosis damage to children in the affected areas, and consolidate the achievements of prevention and control.