Objective: To investigate the incidence and independent risk factors of adverse events (AEs) associated with therapeutic plasma exchange (TPE) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to provide evidence to support the safe use of TPE in clinical practice. Methods: This retrospective study included 167 allo-HSCT recipients who underwent a total of 385 TPE procedures between March 2022 and December 2023. Patients were divided into two groups according to the occurrence of TPE-related AEs. Baseline characteristics, plasma exchange parameters, and clinical features were collected. Univariate analysis and multivariable Firth logistic regression were performed to identify independent risk factors for AEs. Results: A total of 385 TPE procedures were performed in 167 allo-HSCT patients, and 33 patients (19.8%) experienced TPE-related AEs. Among the 33 patients who experienced AEs, allergic reactions were the most common (n=18, 54.5%), followed by blood pressure fluctuations (n=11, 33.3%) and hypocalcemia (n=4, 12.1%). Most AEs were classified as grade II (n=23, 69.7%), and no grade IV (fatal) events were observed. Univariate analysis demonstrated a significant difference in the incidence of AEs among different hematocrit (HCT) categories (<20%, 20%-30%, and>30%) (Fisher's exact test, P=0.022). Although the overall difference was statistically significant, none of the pairwise comparisons remained significant after Bonferroni correction (adjusted P>0.0167). Multivariable Firth logistic regression identified higher HCT levels, analyzed as a continuous variable (OR=1.07, 95% CI: 1.01-1.13, P=0.020), and TPE performed for cytokine release syndrome (CRS) (OR=9.21, 95% CI: 1.25-78.00, P=0.030) as potential independent risk factors for TPE-related AEs. Receiver operating characteristic (ROC) curve analysis showed that HCT had an AUC of 0.67 (95% CI: 0.57-0.77) for predicting AEs, with an optimal cutoff value of 24.5%, a sensitivity of 60.6%, and a specificity of 75.4%. Using this cutoff, the AEs rate was significantly higher in patients with HCT≥24.5% than in those with HCT<24.5% (37.7% vs 11.4%, P<0.001). Conclusion: A-mong allo-HSCT patients receiving TPE, allergic reactions were the predominant AEs. Higher HCT levels and TPE performed for CRS may be associated with an increased risk of AEs. HCT≥24.5% may help identify patients requiring intensified monitoring, although its discriminatory ability is moderate (AUC=0.67) and it should not be used as a standalone criterion for clinical decision-making. Findings regarding the CRS subgroup require validation in larger cohorts. Optimizing extracorporeal circuit priming and strengthening peri-procedural monitoring may help improve the safety of TPE.

Objective : To investigate the antidepressant effects and the underlying mechanisms of tetrahydrocurcumin(THC) and its nanoparticle formulation(THCN). Methods : Forty-six male ICR mice were randomly divided into Con group, LPS group, THC group, THCN group and SER group. A mouse depression model was established by intraperitoneal administration of LPS. The anxiety and depression-like behaviors of mice were evaluated by open field test(OFT) and forced swimming test(FST). Myelin staining was applied to assess the extent of demyelination in the prefrontal cortex of the mice. The prefrontal cortex and hippocampus were further examined for the expression levels of glial fibrillary acidic protein(GFAP) and Toll-like receptor 4(TLR4) through quantitative immunofluorescence assays. Results : Compared with the Con group, the LPS group showed increased anxiety-like and depressive-like behaviors in both the long-term and short-term experiments(P<0.05); the degree of demyelination increased in the LPS group of the long-term experiment(P<0.01); the expression of GFAP was reduced in the LPS group of the short-term experiment(P<0.01), while the expression of TLR4 increased(P<0.05); the expression of TLR4 decreased in the THC group(P<0.01); the expression of GFAP in the prefrontal cortex of the THCN group was reduced(P<0.01), while the expression of TLR4 increased(P<0.05). Compared with the LPS group, the THC group showed reduced depressive-like behaviors in the long-term experiment(P<0.05), while the anxiety-like and depressive-like behaviors of the THCN group and the SER group were reduced(P<0.05), and the anxiety-like and depressive-like behaviors of the THC group and the THCN group were reduced in the short-term experiment(P<0.05); the degree of demyelination was reduced in the THC group, THCN group and SER group in the long-term experiment(P<0.05); the expression of GFAP increased in the THC group of the short-term experiment(P<0.05), while the expression of TLR4 was reduced(P<0.05), and the expression of GFAP increased in the THCN group(P<0.05). Compared with the THC group, the THCN group and the SER group showed reduced anxiety-like behaviors in the long-term experiment(P<0.05); the expression of GFAP in the prefrontal cortex of the THCN group was reduced in the short-term experiment(P<0.05), while the expression of TLR4 in the hippocampal DG area increased in the short-term experiment(P<0.01). Conclusion Tetrahydrocurcumin and its nanoparticle formulation both exert significant ameliorative effects on depression-like behaviors and demyelination in mice induced by lipopolysaccharide. The antidepressant mechanism of THC appears to be mediated through the down-regulation of TLR4 and the up-regulation of GFAP. The mechanism underlying the antidepressant action of THCN seems predominantly focused on the enhancement of GFAP expression.

OBJECTIVE: To evaluate the clinical significance of a hemizygous c.1042-10G>C variant of the SLC9A7 gene NM_001257291.2) previously identified in individuals with neurodevelopmental disorders, and to provide an evidence-based guidance for prenatal genetic counseling. METHODS: Four families presented at the Medical Genetics Center of Henan Provincial People's Hospital between December 2022 and July 2024 were included in this study. Phenotypic information and biological samples were collected from family members. Genomic DNA was extracted and subjected to whole-exome sequencing and copy number variation analysis to identify candidate pathogenic variants. Sanger sequencing was performed for familial co-segregation analysis. Reverse-transcription PCR was used to assess the RNA splicing pattern of the variant in peripheral blood samples. Quantitative PCR was employed to analyze the expression profiles of various SLC9A7 transcripts in fetal brain tissue and peripheral blood samples. Pathogenicity of the variant was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: Six hemizygous males carrying the SLC9A7 c.1042-10G>C variant were identified among the four families, which included three adult males and two male infants with normal phenotypes. Only one affected male from family 3 exhibited global developmental delay, short neck, webbed neck, ocular dysplasia, and congenital corneal leukoma. He also had a history of perinatal asphyxia and carried an additional hemizygous variant HUWE1 c.12283C>G. Reverse-transcription PCR showed no aberrant splicing in heterozygous or hemizygous carriers compared to healthy controls, suggesting that the variant does not affect RNA splicing. Quantitative PCR revealed that NM_001257291.2 is the predominant transcript expressed in fetal brain tissue and peripheral blood. CONCLUSION The SLC9A7 c.1042-10G>C variant does not alter RNA splicing and is present in multiple phenotypically normal males, which supported its classification as a benign variant.
Humans ; Male ; Female ; Genetic Counseling ; Pedigree ; Adult ; DNA Copy Number Variations/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of an infertile woman carrying a novel PADI6 gene variant. METHODS: An infertile woman who visited the Medical Genetics Center of Henan Provincial People's Hospital on April 29, 2024 was selected as the study subject. Clinical data of the proband and her family members were collected. Peripheral blood samples were obtained from the proband and her husband for genomic DNA extraction. Whole-exome sequencing (WES) was performed. Candidate variant was verified among the family members by Sanger sequencing. The pathogenicity of candidate variant was classified according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants. Relevant literature on the pathogenic variants of the PADI6 gene was reviewed for genotype-phenotype correlation analysis. This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital (Ethics No.: 2021-171). RESULTS: The proband was a 35-year-old woman who underwent two oocyte retrieval cycles, yielding a total of five oocytes, with all embryos arrested at day 3 post-fertilization. WES identified a homozygous PADI6 variant, c.367+4_367+7del. In vitro splicing assay confirmed that this variant can cause skipping of exon 3, leading to a frameshift and alterations in the protein structure or premature termination of translation. Literature review identified 12 relevant publications, and the PADI6 c.367+4_367+7del was determined to be a novel variant. CONCLUSION The homozygous PADI6 c.367+4_367+7del variant probably underlay the pathogenesis of infertility in the proband.
Humans ; Female ; Infertility, Female/genetics* ; Adult ; Protein-Arginine Deiminase Type 6/genetics* ; Pedigree ; Exome Sequencing ; Mutation

Objective: To investigate the characteristics and HIV confirmed positive status among individuals attending HIV voluntary counseling and testing (VCT) clinics in Inner Mongolia Autonomous Region, so as to provide the basis for enhancing interventions targeting high-risk populations for AIDS. Methods: Demographic information, reasons for consultation, consulting institutions, and HIV antibody testing data of individuals attending VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023 were collected through the VCT database of the Chinese Center for Disease Control and Prevention. The characteristics of individuals attending VCT were described. Factors affecting HIV confirmed positive among VCT clinic attendees were analyzed using a multivariable logistic regression model. Results: A total of 249 919 individuals attended VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023, including 128 069 males (51.24%) and 121 850 females (48.76%). The majority of attendees were aged 25-<35 years, accounting for 92 445 cases (36.99%). Among them, 785 cases were confirmed as HIV positive, with a positivity rate of 0.31%. Multivariable logistic regression analysis revealed that males (OR=4.787, 95%CI: 3.562-6.434), 45-<65 years of age (45-<55 years, OR=7.723, 95%CI: 1.786-33.406; 55-<65 years, OR=7.689, 95%CI: 1.757-33.653), being unmarried (OR=2.143, 95%CI: 1.580-2.906), junior high school education or below (OR=1.147, 95%CI: 1.042-2.430), having the history of high-risk behaviors or exposure risks (commercial heterosexual behaviors, OR=2.717, 95%CI: 1.707-4.324; non-commercial non-fixed heterosexual behaviors, OR=5.421, 95%CI: 3.763-7.809; homosexual behaviors, OR=70.774, 95%CI: 48.409-103.473; having an HIV-positive spouse/fixed partner/mother, OR=100.024, 95%CI: 62.490-160.100; drug injection, OR=5.366, 95%CI: 2.213-13.014), and seeking general hospitals or traditional Chinese medicine hospitals (OR=1.973, 95%CI: 1.650-2.360) were associated with a higher risk of HIV confirmed positive. Conclusions HIV confirmed positive among individuals attending VCT clinics in Inner Mongolia Autonomous Region is associated with gender, age, marital status, educational level, reasons for consultation, and consulting institutions. It is recommended to strengthen health education and targeted interventions for high-risk populations to reduce the risk of HIV infection.

Objective:To assess the disease burden of lung cancer associated with occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in China from 1990 to 2021 using the 2021 Global Burden of Disease (GBD) data.Methods:In July 2024, data on occupational PAHs exposure-associated lung cancer from 1990 to 2021 were extracted from the GBD database, including mortality rates, age-standardized mortality rates, number of deaths, disability-adjusted life years (DALYs) rates, age-standardized DALYs rates, and number of DALYs for different genders and ages. Descriptive statistics were used to analyze trends in lung cancer mortality rates, age-standardized mortality rates, DALYs rates, and age-standardized DALYs rates over different years, genders, and ages. Joinpoint regression models were used to calculate the annual percent change (APC) and average annual percent change (AAPC), and to identify change points and trends in different periods within the data.Results:From 1990 to 2021, the mortality rate of lung cancer associated with occupational PAHs exposure increased from 0.085 per 100000 to 0.259 per 100000, and the age-standardized mortality rate increased from 0.107 per 100000 to 0.162 per 100000. The DALYs rate increased from 2.746 per 100000 to 7.389 per 100000, and the age-standardized DALYs rate increased from 3.330 per 100000 to 4.679 per 100000. The number of lung cancer deaths and DALYs both peaked in the 65-69 age group. Joinpoint regression analysis showed significant upward trends in mortality, age-standardized mortality, DALYs rate, and age-standardized DALYs rate from 1990 to 2021, with AAPCs of 3.655%, 1.382%, 3.256%, and 1.108%, respectively (all P<0.001). From 2016 to 2021, both the mortality rate and age-standardized mortality rate increased, with APCs of 4.163% and 1.735%, respectively. From 2015 to 2021, the DALYs rate increased (APC: 3.137%), and from 2016 to 2021, the age-standardized DALYs rate also rose (APC: 1.578%). For females, both mortality and DALYs rates increased from 2015 to 2021 (APCs: 6.269% and 5.426%, respectively). Among males, the mortality rate increased from 2018 to 2021 (APC: 3.477%) . Conclusion:From 1990 to 2021, the disease burden of lung cancer related to occupational PAHs exposure in China has significantly increased, particularly among the elderly population. Public health policies should enhance screening and prevention efforts targeting the high-risk populations.

Objective:To evaluate the application effect of intelligent management of health management (examination) institutions in Shanxi Province.Methods:In this study, a cross-sectional study was adopted. In October 2023, through convenient sampling, 300 health management (examination) institutions in Shanxi Province were investigated according to the four regions of northern Shanxi, central Shanxi, southern Shanxi and southeastern Shanxi, and the application information of intelligent management in the whole process from January to December 2022 was collected. According to the evaluation indicators in the documents of the National Health and Wellness Commission, six indicators were analyzed, including the completion rate of health questionnaire, the integrity of physical examination files, the filing rate of physical examination cycle, the evaluation rate of cardiovascular risk diseases, the re-examination rate of patients with chronic diseases (blood pressure, blood lipid and blood glucose indicators) and the follow-up rate of important abnormal results.Results:The completion rates of health questionnaires in northern Shanxi, central Shanxi, southern Shanxi and southeastern Shanxi were 54.9%, 84.2%, 93.2% and 98.2% ( χ 2=225 050.17, P<0.001), and the filing rates of health checkups in various regions were 89.1%, 94.7%, 94.0% and 94.5% ( χ 2=10 254.02, P<0.001). The filing rates of physical examination cycles in each region were 21.8%, 23.4%, 24.3% and 24.7% ( χ 2=734.15, P<0.001), and the assessment rates of cardiovascular risk diseases in each region were 84.5%, 85.4%, 80.2% and 86.2% ( χ 2=4 627.99, P<0.001). The reexamination rates of patients with chronic diseases (blood pressure, blood lipid and blood glucose indicators) in different regions were 38.8%, 39.7%, 39.3% and 39.5% ( χ 2=24.24, P<0.001), and the follow-up rates of important abnormal results were 81.7%, 84.1%, 82.9% and 83.9% ( χ 2=255.02, P<0.001). Conclusion:Shanxi health management (examination) institutions have achieved certain results in the application of intelligent management in the whole process, but there is still much room for improvement in the filing of physical examination cycle and re-examination of chronic diseases.

Objective:To understand the incidence and epidemiological characteristics of enteritis due to norovirus infection in Guizhou Province from 2016 to 2023, and provide reference for the prevention and control of enteritis caused by norovirus.Methods:The data were from National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention. To collect the data of other infectious diarrhea cards in Guizhou from 2016 to 2023, which were annotated as enteritis due to norovirus and food-borne disease surveillance sentinel report in Guizhou, which were positive for norovirus detection. The data of cluster/outbreaks were from the Public Health Emergency Event Surveillance System and the field investigation reports of CDC at all levels. Descriptive epidemiological method was used to describe the characteristics of its three-dimension distribution, epidemic situation and pathogen spectrum. R 4.2.2 software was used for statistical analysis.Results:A total of 2 340 cases of enteritis due to norovirus were reported in Guizhou Province during this period, with an average annual reported incidence of 0.79/100 000, and the incidence showed an upward trend (trend χ2=1 723.80, P<0.001). The high incidence season is from October to March (winter and spring). The male to female ratio of the cases was 1.39∶1 (1 362∶978). A total 1 382 cases occurred in age group under 5 years old (59.06%) and 1 249 cases occurred in children living scatteredly (53.38%). The average annual reported incidence in 6 prefectures (muniipality)(1.15/100 000 in Qiandongnan Miao and Dong Autonomous Prefecture, 1.08/100 000 in Guiyang, 1.07/100 000 in Liupanshui, 1.06/100 000 in Qianxinan Buyi and Miao Autonomous Prefecture, 0.91/100 000 in Qiannan Buyi and Miao Autonomous Prefecture and 0.89/100 000 in Tongren) in Guizhou Province was higher than provincial level, and the affected areas gradually expanded from southeastern counties (districts) to western and northern counties (districts). The average annual reported incidence rate was higher in urban area (1.12/100 000) than in rural area (0.39/100 000). A total of 31 cluster/outbreaks of enteritis due to norovirus were reported, in which 83.87% (26/31) occurred in child care settings, primary and secondary schools, in which 74.19% (23/31) were caused by human-to-human transmission. In the 2 340 cases, 2 147 were laboratory diagnosed (91.75%), and 193 were clinically diagnosed (8.25%). In the laboratory diagnosed cases, 2 026 (94.36%) were caused by single norovirus infection and 121 (5.64 %) were caused by mixed infection. Conclusions:On the whole, the incidence of enteritis due to norovirus in Guizhou Province was on the rise from 2016 to 2023, and winter and spring were the high incidence seasons. Effective prevention and control measures should be taken for key populations, key regions and key places, and multi-channel and multi-pathogen surveillance and health education should be strengthened.

Objective : To investigate the therapeutic effects and underlying mechanisms of cannabidiol(CBD) and its nano-formulations on depression-like behaviors in mice. Methods : A murine model of acute anxiety and depression was established by intraperitoneal administration of lipopolysaccharide(LPS). A total of 55 mice were randomly assigned into several groups: for the long-term study, a control group(Con), a model group(LPS), a cannabidiol group(CBD), a nano-cannabidiol group(NCBD), and a sertraline(SER) group, each consisting of 7 mice. In the short-term study, mice were divided into four groups: the Con group, LPS group, CBD group, and NCBD group, with 5 mice in each group. Except for the Con group and LPS group, which were given distilled water, the remaining groups were administered 25 and 50 mg/kg of cannabidiol and its nano-formulationviaoral gavage. The open field and forced swimming tests were employed to assess anxiety-and depression-like behaviors inmice. Luxol Fast Blue myelin staining was employed to evaluate myelin sheath morphology in the prefrontal cortex, and immunofluorescence staining was utilized to quantify the protein expression levels of silencing information regulator(SIRT2), ionized calcium binding adaptor molecule-1(Iba-1), and interleukin-1β(IL-1β) in the prefrontal cortex. Results : In the long-term experiment, the LPS group exhibited a significant reduction in shuttle times(P<0.05), an increase in immobility time(P<0.01), and a decrease in the number and length of myelin sheaths(P<0.05) compared to the Con group. Compared to the LPS group, the depressive behaviors in the CBD, NCBD, and SER groups were significantly alleviated(P<0.01), and the number and length of myelin sheaths increased(P<0.05). In the short-term experiment, compared to the Con group, the LPS group exhibited significantly increased anxiety-and depression-like behaviors(P<0.05), downregulated SIRT2 expression(P<0.01), and upregulated Iba-1 and IL-1β expression(P<0.01). The CBD and NCBD groups demonstrated a reduction in anxiety and depression-like behaviors(P<0.05), an increase in SIRT2 expression(P<0.01), and a decrease in Iba-1 and IL-1β expressions(P<0.05) compared to the LPS group. Conclusion CBD and its nano-formulations effectively mitigate anxiety and depression-like behaviors in mice. The underlying mechanisms may be associated with the reversal of SIRT2 protein expression, demyelination changes, microglial activation, and the levels of inflammatory factors in the prefrontal cortex.

Objective To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation(AF),and to evaluate the predictive value of SNORD55 for prognosis.Methods A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study.Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected.Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients.The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients.The area under the receiver operating characteristic curve(AUC)was utilized to evaluate the discrimination,and the net reclassification index(NRI)and comprehensive discriminant improvement index(IDI)were calculated to evaluate the improvement of reclassification ability.Decision curve analysis(DCA)was applied to analyze the change in clinical net benefit.Results The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients.In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value[0.80(95％CI:0.67～0.93)vs 0.67(95％CI:0.53～0.81),P＜0.05].In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI[54.3(95％CI:10.6～61.9)vs 31.9(95％CI:2.8～47.5),P＜0.05]and IDI[16.1(95％CI:2.4～27.0)vs 7.9(95％CI:0.5～14.8),P＜0.05].The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.Conclusion Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.