Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.

Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.

Aim To study the mechanism of adipose mesenchymal stem cell exosomes(ASC-exo)inhibition of fluorescein isothiocyanate(FITC)-induced atopic dermatitis(AD).Methods The mouse age,extrac-tion method,and the concentration of a solution of typeⅠ collagen enzyme and other conditions were compared to study the effects on the morphology and quantity of adipose mesenchymal stem cells(ASCs)after extrac-ted.FITC-induced mouse model in vivo was estab-lished and different doses of ASC-exo were given to measure ear thickness,ear weight and ear scratching times of mice.HE staining was used to observe the pathological changes of ear tissue of mice.The non-toxicity of ASC-exo was detected.IgE,IL-5,IL-13 and other cytokines were detected by ELISA.The gene ex-pressions of TSLP,IL-33,occludin,Claudin-1(CLDN-1)and E-cadherin were detected by RT-qPCR.The protein expression was detected by immunohistochemis-try.Results An efficient method for extracting ASCs was established.Compared with the blank group,mice in the model group showed obvious AD symptoms.Compared with the model group,ASC-exo administra-tion group significantly reduced the number of ear scratches,epidermal thickening,inflammatory cell infil-tration and the secretion of Th2 cytokines IL-5 and IL-13.Meanwhile,ASC-exo administration group signifi-cantly increased the expression of structural proteins CLDN-1 and occludin in epithelial cells and decreased the expression of TSLP and IL-33.Conclusions ASC-exo can significantly improve Th2 skin inflamma-tion in AD mice,and its mechanism may be through in-creasing the expression of tight junction proteins and adhesion link protein in epithelial cells,repairing the skin barrier,and inhibiting the key promoters of allergy TSLP and IL-33.

Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of autism spectrum disorder (ASD). Methods: A longitudinal study was conducted. Clinical data from ASD patients with gastrointestinal symptoms and who underwent FMT in the Tenth People's Hospital affiliated to Tongji University or Jinling Hospital between May 2012 to May 2021 were retrospectively collected. Scores derived from the autism behavior checklist (ABC), the childhood autism rating scale (CARS), the Bristol stool form scale (BSFS), and the gastrointestinal symptom rating scale (GSRS) were analyzed at baseline and at the 1st, 3rd, 6th, 12th, 24th, 36th, 48th and 60th month after FMT. Records of any adverse reactions were collected. Generalized estimating equations were used for analysis of data on time points before and after FMT. Results: A total of 328 patients met the inclusion criteria for this study. Their mean age was 6.1±3.4 years old. The cohort included 271 boys and 57 girls. The percentage of patients remaining in the study for post-treatment follow-up at the 1st, 3rd, 12th, 24th, 36th, 48th and 60th month were as follows: 303 (92.4%), 284 (86.7%), 213 (64.9%), 190 (57.9%), 143 (43.6%), 79 (24.1%), 46 (14.0%), 31 (9.5%). After FMT, the average ABC score was significantly improved in the first 36 months and remained improved at the 48th month. However, the average score was not significantly different from baseline by the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.108). The average CARS score improved significantly during the first 48 months and remained improved at the 60th month (1st-48th month, P<0.001; 60th month, P=0.010). The average BSFS score was also significantly improved in the first 36 months (with an accompanying stool morphology that resembled type 4). This improvement was maintained at the 48th month. However, the average score was similar to baseline at the 60th month (1st-36th month, P<0.001; 48th month, P=0.008; 60th month, P=0.109). The average GSRS score was significantly improved during the first 24 months, but not afterwards (1st-24th month, P<0.001; 36th month, P=0.209; 48th month, P=0.996; 60th month, P=0.668). The adverse events recorded during treatment included abdominal distension in 21 cases (6.4%), nausea in 14 cases (4.3%), vomiting in 9 cases (2.7%), abdominal pain in 15 cases (4.6%), diarrhea in 18 cases (5.5%), fever in 13 cases (4.0%), and excitement in 24 cases (7.3%). All adverse reactions were mild to moderate and improved immediately after suspension of FMT or on treatment of symptoms. No serious adverse reactions occurred. Conclusion: FMT has satisfactory long-term efficacy and safety for the treatment of ASD with gastrointestinal symptoms.
Autism Spectrum Disorder/therapy* ; Child ; Child, Preschool ; Fecal Microbiota Transplantation/adverse effects* ; Feces ; Female ; Gastrointestinal Diseases ; Humans ; Longitudinal Studies ; Male ; Retrospective Studies

Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.
Adult ; Blood Component Removal/methods* ; Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; Hyperlipoproteinemia Type II/therapy* ; Lipoprotein(a)/chemistry* ; Lipoproteins/chemistry* ; Male ; Middle Aged ; Retrospective Studies

Xiehuangsan， derived from QIAN Yi's Key to Therapeutics of Children's Diseases， consists of 5 medicines， namely Gypsum Fibrosum，Gardeniae Fructus，Saposhnikoviae Radix，Pogostemonis Herba and Glycyrrhizae Radix et Rhizoma. It is used to treat children with spleen heat and tongue scratching. With the clinical use of later generations of physicians，the scope of diseases and syndromes of this prescription was gradually expanded，including aphthous bad breath，dry lips，yellow eyes，and sweet mouth. Modern doctors used this prescription to treat children with anorexia，constipation，allergic purpura，tic disorder， and other diseases. At present，more and more attention has been paid to the research of classical famous prescriptions. At the same time，the application of classical famous prescriptions of traditional Chinese medicine（TCM） must be researched and verified in ancient literature. Therefore，it has become important contents in the study of classic prescriptions that researching the source of prescriptions from the ancient books，combing and analyzing literature，and studying the evolution rules of indications，preparations，methods of administration and taboos.The author searched a variety of ancient Chinese medicine databases and collected the relevant documents related to Xiehuangsan in ancient medical books. A total of 242 pieces of relevant ancient document data were obtained，involving 131 types of ancient Chinese medicine books. Through combing the relevant records of historical documents，this paper analyzes and researches the historical evolution of Xiehuangsan，the source and composition of the prescriptions，the indications，the dosage，the textual research of Chinese herbal medicine and the determination of the basis，and the method of prescription preparation and administration，etc. The historical changes of Xiehuangsan and its internal relations are expected to provide literature references and theoretical basis for the modern development and research of Xiehuangsan.

BACKGROUND: Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people. METHODS: A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%-95%) were determined for reference ranges in different populations. RESULTS: There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = -14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = -0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age. CONCLUSIONS Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

"TCM syndrome of plague attack lung" is a classification of traditional Chinese medicine syndromes of the novel coronavirus pneumonia by the Beijing Municipal Administration of Traditional Chinese Medicine. In this study, a mouse model combining disease with syndrome of human coronavirus pneumonia with cold-dampness pestilence attacking the lung was established for the first time, and the therapeutic effect of matrine sodium chloride injection was evaluated based on immune regulation and inflammatory damage. Lung index, lung index inhibition rate and HE stain were used to evaluate the therapeutic effect of matrine sodium chloride injection on the model mice; the viral load in lung tissue was measured by RT-PCR to evaluate its antiviral effect; the percentage of CD4⁺ T cells, CD8⁺ T cells and B cells were detected by flow cytometry to evaluate its immunomodulatory effect; the production of interleukin 6 (IL-6), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA to evaluate its anti-inflammatory effect. All interventions and operations in the experiment were approved by the Animal Ethics Committee of the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, and conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH) and Beijing Experimental Animal Ethics Committee. The results showed that intraperitoneal injection of the high-dose (36.67 mL·kg^-1·d^-1) and low-dose (18.33 mL·kg^-1·d^-1) of matrine sodium chloride injection significantly improved the pathological damage of lung tissue and reduced lung index. The lung index inhibition rates were 86.86% and 76.53%, respectively. The production of IL-6, IL-10, TNF-α, IFN-γ, as well as the viral load in lung tissue were reduced significantly compared to the model; the percentage of CD4⁺ T cells, CD8⁺ T cells and B cells in peripheral blood were increased compared to the model. These results indicated that the matrine sodium chloride injection has an evident therapeutic effect on the model, and its mechanism was related to the inhibition virus replication, regulation of immunity function and inhibition of inflammatory factor release. This study provided laboratory data support for matrine sodium chloride injection which was used to treat the novel coronavirus pneumonia in clinical in Hubei province. These results indicated that the matrine sodium chloride injection has a good prospect for prevention and treatment of the novel coronavirus pneumonia.