Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Objective To explore the effect of Shexiang Baoxin pill on cardiac tissue angiogenesis in spontaneously hypertensive rats(SHR).Method Twenty 12 week old male SHR were randomly divided into experimental group and model group,with 12 week old male SD rats as the normal control group.The experimental group rats were orally administered with Shexiang Baoxin pill(45 mg·kg-1)daily,and their blood pressure was monitored using a non-invasive tail artery blood pressure gauge every four weeks.Eight weeks later,cardiac tissue was taken for platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)immunofluorescence staining to observe CD31 expression level.Use protein blotting to detect the expression levels of myocardial endothelial growth factor(VEGF),myocardial endothelial growth factor receptor 2(VEGF-R2),basic fibroblast growth factor(bFGF)and phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)proteins.Result There was significant increase in blood pressure between the experimental group,model group and normal group at the same time point(all P＜0.01),but there was no statistically significant difference in blood pressure changes between the experimental group and model group at the same time point(all P＞0.05).The CD31 expression rates of the normal group,model group and experimental group were(3.79±0.84)％,(2.54±0.42)％and(3.56±0.49)％;VEGF levels were 0.95±0.10,0.73±0.08 and 0.94±0.15;VEGF-R2 levels were 0.85±0.10,0.61±0.14 and 0.80±0.10;bFGF levels were 0.84±0.04,0.51±0.21 and 0.74±0.14;p-Akt/Akt levels were 0.85±0.15,0.57±0.13 and 0.80±0.20,respectively.The differences between the normal group and the model group,as well as the experimental group and the model group,were statistically significant(all P＜0.05).Conclusion Shexiang Baoxin pill can promote the neovascularization of microvessels in the heart tissue of spontaneously hypertensive rats,and its mechanism may be related to the activation of PI3K/Akt phosphorylation,upregulation of bFGF,VEGF and their receptor VEGF-R2 in myocardial tissue.

Objective: To investigate the factors affecting depression and anxiety symptoms among the elderly, so as to provide the basis for promoting mental health among the elderly. Methods: The elderly aged 60 years and above in Ningbo City, Zhejiang Province were recruited using the multistage stratified random sampling method from June to August 2022, and demographic information, lifestyle and self-rated health status were collected by questionnaires. The symptoms of depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7), respectively. The presence of depressive and anxiety symptoms was determined when both the PHQ-9 score and the GAD-7 score were 10 points and higher. Factors affecting depressive and anxiety symptoms were identified using a multivariable logistic regression model. Results: A total of 7 771 individuals were surveyed, including 3 490 males (44.91%) and 4 281 females (55.09%), and had a mean age of (72.11±6.79) years. The prevalence of depression and anxiety symptoms was 2.05%. Multivariable logistic regression analysis identified residence (urban area, OR=0.316, 95%CI: 0.201-0.498), sedentary duration (<3 h/d, OR=0.349, 95%CI: 0.232-0.525; 3-5 h/d, OR=0.458, 95%CI: 0.313-0.671), physical activity (≥3 times/week, OR=0.551, 95%CI: 0.373-0.815), sleep quality (poor, OR=2.491, 95%CI: 1.738-3.571), social isolation (OR=1.688, 95%CI: 1.148-2.481) and self-rated health (poor, OR=5.857, 95%CI: 3.547-9.671; normal, OR=1.903, 95%CI: 1.234-2.937) as the influencing factors for depression and anxiety symptoms among the elderly. Conclusion The prevalence of depression and anxiety symptoms among the elderly is associated with residence, sedentary duration, sleep quality, physical activity, social interactions and self-rated health status.

Objective To explore the selection rules of acupuncture and moxibustion for treating ovarian dysfunction-related diseases by applying data mining technology.Methods Computer searches were conducted to find clinical research literature on acupuncture and moxibustion for ovarian reserve dysfunction-related diseases(including diminished ovarian reserve,premature ovarian insufficiency,premature ovarian failure)in major databases,such as China National Knowledge Infrustructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and China Science and Technology Journal Database(VIP),Excel 2021 was used to establish a prescription database of acupoints selection,and SPSS Modeler 18.0 and SPSS Stastics 26.0 software were used to analyse the frequency,meridian tropism,site,special acupoints,analysis of association rule,and cluster analysis of acupoints to study the rules of acupuncture and moxibustion for treating ovarian reserve dysfunction-related diseases.Results A total of 215 articles were screened to meet the requirements,in which,96 acupoints were used,with a total frequency of 2 110 times.The high-frequency used acupoints were Guanyuan(RN4),Sanyinjiao(SP6),and Shenshu(BL23),etc,.The commonly used meridians were the conception vessel(CV)and bladder meridian of foot-taiyang,and the acupoints were mostly located in the abdomen and lower limbs,with the majority being the five-shu point and the yuan front-mu points.The core acupoints and four effective clusters were analysed.Conclusion The acupoint selection of acupuncture and moxibustion for ovarian reserve dysfunction-related diseases focuses on tonifying qi and blood,cultivating the vital essence and tonifying the kidneys.Most of the meridians related to reproduction were selected in this method,which aiming at regulating menstruation and tonifying blood,and pre-cultivating its loss.This research focuses on the matching of neighboring point and distant point selection,and pays attention to the use of specific acupoints,and treates multiple organs simultaneously.

Objective:To analyze the effect of peripheral blood hematopoietic stem cells(PBSC)collection from unrelated donors and its influencing factors.Methods:A retrospective analysis was conducted on the mobilization and collection of PBSC from 113 unrelated donors at Yueyang Central Hospital from January 2021 to December 2023.Results:113 donors were successfully mobilized.The average count of PBSC mononuclear cells(MNC)and CD34+cells were(12.40±7.41)x 108/kg and(10.64±8.07)x 106/kg,respectively.Univariate analysis showed that the PBSC CD34+cells ratio of male donors was significantly higher than that in female donors(P=0.015).The peripheral blood(PB)white blood cell(WBC)count before collection was positively correlated with the PBSC nucleated cells count(r=0.388),and the donor's body weight,the PB CD34+cell ratio before collection were positively correlated with the PBSC CD34+cell ratio(r=0.259,r=0.780).The daily dose of rhG-CSF was negatively correlated with the PBSC CD34+cell ratio(r=-0.285).Both rhG-CSF agents achieved successful mobilization.Multivariate analysis showed that PB WBC count before collection was a factor affecting the count of PBSC nucleated cells(P＜0.001),while the PB CD34+cell ratio before collection was a factor affecting the PBSC CD34+cell ratio(P＜0.001).Conclusion:The mobilization and collection of PBSC from unrelated donors are good,and the PB WBC count and CD34+cell ratio before collection are reliable indicators for predicting the collection effect.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

ObjectiveTo explore a new model for lens-induced myopia （LIM） in mice and describe the changes of diopter and ocular biological parameters. MethodsTwenty-seven 21-day-old C57BL/6 mice were divided into three groups （ratio， 5：1：3）： LIM group， plano lens （PL） group and normal control （N） group. The right eyes were intervened while the left eyes were left as control. The refraction was detected with retinoscopy after the pupils were dilated with compound topicamide and ocular axial length was measured by optical coherence tomography （OCT） in vivo at baseline and 1， 2， 3， and 4 weeks after the intervention. Paired t test was performed between left and right eyes within each group. Welch's ANOVA was used for comparison among the three groups. When the difference was statistically significant， the Dunnett's T3 was used to correct P value for pairwise comparison. ResultsAfter 2 weeks of defocus induction， the refraction of the intervened eye in LIM group shifted to myopia about （-2.55±1.54） D（t=6.430， P＜0.000 1）， and the ocular axial length （AL） increased about （0.051±0.024） mm（t=7.837， P＜0.000 1）. The difference of interocular change in refraction in LIM group compared with PL group and N group was -2.30 D （P=0.014） and -2.55 D （P＜0.000 1）， respectively. The difference of interocular change in AL in LIM group was 0.048 mm （P<0.000 1） and 0.047 mm （P<0.000 1） compared with that in PL group and N group， respectively. With the extension of intervention time， the degree of myopia drift increased. ConclusionIn this study， a clasp-based and detachable LIM model was described and validated. After 2 weeks of intervention， the refraction shifted significantly toward myopia and the AL increased significantly. The LIM model is simple to construct and can provide a reference for the model construction of animal experiments in myopia research.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing