This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Objective To develop a biological safety protection third-level(BSL-3)laboratory based on folding-modular shelters to solve the problems of the existing laboratories in space and function expansion,large-scale deployment and low-cost transportation.Methods The BSL-3 laboratory was composed of a folding combined shelter module,a ventilation and purification module,a power supply and distribution module,a monitoring and communication module,a control system module and an equipment module.The folding combined shelter module used a leveling base frame as the foundation and a lightweight panel as the enclosure mechanism,and was divided into an auxiliary area and a protection protected area;the ventilation and purification module was made up of an air supply unit and an air exhaust unit,the air supply unit was integrated with a fresh-air air conditioner and the exhaust unit was equipped with a main fan,a standby fan and a bag in/bag out filter;the control system module adopted a supervision mode of decentralized control and centralized management,which executed communication with the data server as the center and Profinet protocol and MODBUS-TCP.Results The BSL-3 laboratory proved to meet the requirements of relevant standards in internal microenvironment,airflow direction,airtightness,working condition and disinfection effect.Conclusion The BSL-3 laboratory is compatible with large-scale transport and deployment and facilitates reliable and safe experiments for epidemic prevention and control and cross-regional support.[Chinese Medical Equipment Journal,2024,45(3):41-46]

Objective To develop a ventilation system for the enhaned mobile biosafety level-2(BSL-2)laboratory to control the dispersed aerosol within the laboratory effectively.Methods A ventilation system for the enhanced mobile biosafety level-2 laboratory was designed with the concept of full fresh air ventilation,which realized air supply with 3-stage filtration and constant air volume control,and air exhaust with 1-stage high-efficiency filtration and variable air volume control.The buffer room had the layout of upside air supply and upside exhaust,with the air supply and exhaust equipment integrated into the ceiling;the experimental room had the layout of diagonally upside air supply and diagonally downside exhaust.Computa-tional fluid dynamics(CFD)software was used to analyze the airflow organization,temperature field and velocity field at 0°,30°,45°,60° and 90° air supply angles in order to verify the feasibility of the ventilation system design,and the distributions of aerosol concentration in the experimental room at different air supply angles were simulated to determine the optimal air supply angle.Results Investigations in terms of airflow organization,temperature field,velocity field and aerosol dispersion control showed in case of 60° air supply angel the enhanced mobile BSL-2 laboratory behaved the best and its core indexes all met the requirements of GB 27421-2015 Mobile laboratories—Generalrequirements for biosafety and T/CESC 662-2020 Architectural technical standard for BSL-2 laboratory in medical facilities including the number of air changes,static pressure difference,temperature and humidity,cleanliness and airflow direction.Conclusion Considerations have to be taken on the locations of supply and exhaust outlets,the facility layout and air supply angle when the enhanced mobile BSL-2 laboratory is designed so as to enhance the biosafety of the protective area.[Chinese Medical Equipment Journal,2024,45(7):29-34]

OBJECTIVE: To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals. METHODS: A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality. RESULTS: Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81). CONCLUSION In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
Humans ; ST Elevation Myocardial Infarction/therapy* ; Percutaneous Coronary Intervention ; East Asian People ; Treatment Outcome ; Myocardial Reperfusion ; Myocardial Infarction ; Registries ; Hospitals

OBJECTIVE: To understand the clinical characteristics about sequence diagnosis and treatment of oral complications in patients with Sjögren's syndrome (SS) through retrospective analysis, and to provide some guidance for clinical work. METHODS: Some SS patients who underwent oral sequence management in the Department of General Dentistry, Peking University School and Hospital of Stomatology from January 2015 to September 2021 were enrolled. For the SS patients included in this study, a comprehensive oral examination was performed, including parotid region examination, oral mucosal exa-mination, dentition examination, dental examination, periodontal examination, unstimulated salivary flow rate, Candida infection and radiological imaging examination. According to the examination results, the patients were given fluoride application, antifungal treatment, root canal therapy, direct filling repair, and indirect repair treatment in sequence and the results recorded. RESULTS: A total of 9 patients with SS, with 4 primary SS patients (pSS) and 5 secondary SS patients (sSS) were enrolled in the study. For all the 9 patients, the average age was (49.2±16.2) years and the median xerostomia duration 5 years. The unstimulated salivary flow rate of the 9 patients was all less than 1 mL/10 min. Eight of the 9 cases was diagnosed as oral Candidiasis, with positive salivary Candida culture result (>200 cfu/mL), and 1 of the 9 cases was not. The average decay, missing, filling teeth (DMFT) was 24.8±4.2; the average decay, missing, filling tooth surfaces (DMFS) was 59.2±21.9, the average incisal caries was 2.5±1.3, and the average number of crown restorations at baseline was 4.5±3.6. All the 9 SS patients were applied with topical fluoride usage, and 8 were prescribed with antifungal treatment. One sSS patient was conducted with filling restoration treatment, one pSS patient was conducted with full mouth rehabilitation, and the remaining 7 patients were conducted with direct filling combined with fixed repair treatment. The average 3.2 full crown restorations in 6 patients had to be removed and restored because of secondary caries, and 3 of the 9 patients underwent implant denture restorations finally. CONCLUSION Management of oral complications in SS patients needs to be carried out in sequence. A comprehensive examination and diagnosis should be carried out first, followed by infection control, and then restoration of oral function at last.
Humans ; Adult ; Middle Aged ; Aged ; Sjogren's Syndrome/complications* ; Retrospective Studies ; Antifungal Agents ; Xerostomia ; Fluorides

Objective To explore the effect and safety of target controlled infusion mode based on precision anesthesia concept in cardiac surgery anesthesia.Methods A total of 100 patients underwent cardiac surgery in our hospital were selected as the research subjects,and they were randomly divided into the control group and the observation group,with 50 cases in each group.The surgical types,surgical related indicators,dosage of anesthetic drugs,and complications of the two groups were compared.Results There was no statistically significant difference in the proportions of patients who underwent coronary artery bypass surgery,valve surgery,macrovascular surgery,artial septal defect repair surgery,or other types of surgery between the two groups(P>0.05).There were statistically significant differences in the surgical time,bleeding volume,infusion volume,proportion of cardiopulmonary bypass,times of postoperative analgesic drug use and mechanical ventilation duration between the two groups(P<0.05).The usage of various anesthetic drugs in the observation group was lower than that in the control group,with statistically significant difference(P<0.05).The incidence of complication in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion The target controlled infusion mode based on precision anesthesia concept can be used for cardiac surgery anesthesia to reduce the dosage of anesthetic drugs and postoperative complications,and improve the anesthesia effect and surgical safety.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To compare the clinical efficacy and safety of hypomenthylating agents (HMA) combined with Venetoclax (VEN) and half dose priming regimen (CAG-like) in the treatment of elderly patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for intensive chemotherapy. METHODS: The clinical data of 43 newly diagnosed elderly patients with AML who were not suitable for intensive chemotherapy in our hospital from April 2019 to October 2020 were retrospectively analyzed. Among them, 16 cases received HMA-VEN regimen and 27 cases received HMA-CAG-like regimen. The remission rate, early mortality and survival were compared between the two groups. And, the patients were grouped according to HCT-CI score. The effects of two different regimens in different groups on the efficacy and survival of patients were compared, and the prognosis of patients was further analyzed. RESULTS: After one course of treatment, the total remission rate of HMA-VEN group and HMA-CAG-like group was 81.3% (13/16) and 51.9% (14/27), respectively, and the difference between the two groups was statistically significant (χ2=4.650, P=0.045). The median overall survival (OS) time of HMA-VEN group had not yet reached, while that of HMA-CAG-like group was 11.2 months, and the HMA-VEN group had a longer OS (P=0.055). There was no tumor lysis syndrome occurred in both groups. The main adverse reactions were digestive tract reaction, bone marrow suppression and infection. The amount of agranulocytosis infection, pulmonary infection and platelet infusion in HMA-VEN group were significantly lower than those in HMA-CAG-like group (P<0.05), while the time of agranulocytosis and amount of erythrocyte infusion were similar (P>0.05). In HMA-Ven group 1 case died early, while in HMA-CAG-like group 8 cases died early due to pulmonary infection, respiratory failure, cerebral hemorrhage, and alveolar hemorrhage, the mortality in HMA-CAG-like group was significantly higher than that in HMA-VEN group (P=0.043). Among 43 patients, there was a significant difference in OS between HCT score 0-2 group and ≥3 group (P=0.033). In HMA-CAG-like group, patients with HCT score ≥3 had a worse prognosis (P=0.01), while in HMA-VEN group patients showed no statistically significant difference in prognosis (P=0.681). In HCT score 0-2 group, 9 cases receiving HMA-VEN regimen and 22 cases receiving HMA-CAG-like regimen showed no statistical difference in OS (P=0.281). In HCT score ≥3 group, 7 cases receiving HMA-VEN regimen had a longer OS than 5 cases receiving HMA-CAG-like regimen (P=0.015). CONCLUSION Venetoclax combined with HMA can achieve higher response rate, lower early mortality, and longer OS, especially in those with more comorbidities and poor tolerability.
Humans ; Aged ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy*

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

OBJECTIVE: To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice. METHODS: In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed. RESULTS: Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05). CONCLUSION HLE may protect against bone loss, and have potentials in the treatment of osteoporosis.