Objective To investigate the clinical typing and staging in diagnosis of Severe Acute Respiratory Syndrome (SARS). Methods Retrospective study was designed to analysis the principal clinical characteristic of SARS and the standard of clinical typing and staging was raised. Comparisons with X-ray in lung, change of lymphocyte subset, PaO_2, SaO_2,and prognosis of disease were performed. Results The standard of SARS clinical typing and staging is four types (light type, ordinary type, heavy type, serious type)and four phases (prodromal period, progres phase, fastigium, recovery phase). The light type is 8/162(4.9%), ordinary type is 69/162 (42.6%), heavy type is 41/162 (25.3%), serious type is (27.2%). Comparisons SARS clinical typing and staging with X-ray in lung, change of lymphocyte subset were found that the more lesion in lung, the lower lymphocyte and its subset, and more serious in clinical typing. Conclusions The standard of clinical typing and staging summarized basic clinical characteristic in SARS, and coincided with progress of SARS. The standard will be help of clinical diagnosis, treatment and judging the prognosis of SARS.

Hypoxia is the most common tumor microenvironment caused by rapid proliferation of tumor cells, and hypoxia-inducible factor (HIF) is the main transcription factor for tumor cells to adapt to hypoxia. Current research has found that HIF can interact with a variety of mesenchymal cells such as fibroblasts, endothelial cells and immune cells in the tumor microenvironment, leading to the transcription and expression of target genes in response to hypoxia, which ultimately promotes tumor angiogenesis, and induces physiological changes such as migration, invasion, and immune escape of tumor cells. However, the signaling pathways involved in the HIF regulatory mechanism are complex, and the mechanism of HIF in the tumor microenvironment need to be further investigated, also most HIF inhibitors are still in the preclinical research stage. This paper reviews the research progress on the effects of HIF on tumor mesenchymal stromal cells to provide a theoretical basis for the diagnosis, prevention and treatment of tumors targeting HIF.

Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight=3.29, RMS=0.53, total cost-null cost=62.75, Correl=0.93, Config=19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.

Objective:To provide the basic data for the further revision of mycoplasma test method described in Chinese Pharma-copoeia and some references for the operation standardization of drug mycoplasma test. Methods:Two incubation conditions,namely aerobic conditions and microaerophilic conditions,were compared with respect to the growth status of mycoplasma in liquid and solid media. Results:The growth of mycoplasma was obvious difference between the two incubation conditions,and the microaerophilic con-ditions were better than the aerobic conditions. Conclusion:The microaerophilic conditions can be used in the incubation of mycoplas-ma test,which should be defined and standardized in the future Chinese Pharmacopoeia.

Microbiological data deviations ( MDD) investigation differs from out of the standard ( OOS) investigation in chemical inspection items. Investigating Out-of-Specification( OOS) Test Results for Pharmaceutical Production issued by FDA specifically ex-cludes microbiological and other biological assays. Until recently, there is not a definitive guideline for MDD investigation in the world. Some institutions and experts have explored the practice and theory of MDD investigation. Referred to the existing practical experience and theoretical achievement and based on the provisions of Chinese GMP (2010 revision) and the requirements of Chinese Pharmaco-poeia Ⅱ(2010 edition) Appendix XIX Q, the article discussed the methods for MDD laboratory investigation.

Objective:To investigate the growth-promoting properties and applicability of the mycoplasma test culture media pre-scribed in Chinese pharmacopoeia, and provide reference for the standardization of the drug mycoplasma test method. Methods: Re-spectively using four quantitative detection methods including sensitivity, degree of color change, colony counts and colony diameter, and mycoplasma media widely used in the world as the reference media, the growth-promoting properties of 4 batches of mycoplasma broth and 4 batches of arginine mycoplasma broth from four domestic manufacturers were investigated. Results:The results of sensitivity assay and absorbance detection showed that all the media inoculated with below 100 CFU test microorganisms exhibited visible color change. Furthermore, the results of color change degree and colony diameter showed that there were significant differences among the media products from different manufacturers(P<0. 01). Conclusion:Mycoplasma broth and arginine mycoplasma broth both can sup-port the growth of below 100 CFU test microorganisms. Due to the difference in the growth-promoting properties among the media prod-ucts from different manufacturers, the drug mycoplasma test workers should use more sensitive methods to examine the applicability of the media.

Objective The purpose of this study was to explore the effect of FVIII(factor VIII,FVIII)and VWF (von Willebrand factor,VWF)elevation on the severity, prognosis and inpatient complications such as infections and neuroworsening in patients with acute ischemic stroke. Methods Ninety patients with acute ischemic stroke and 50 pa?tients without ischemic stroke were recruited from affiliated Shengjing hospital of China Medical University between De?cember 2014 and March 2015 . We tested FVIII and VWF levels of all the patients. Patients with acute ischemic stroke were divided into 4 groups:both FVIII and VWF within normal range(FVIII-/VWF-);elevated FVIII, but normal VWF (FVIII↑/VWF-); FVIII within normal range, but elevated VWF(FVIII-/VWF↑); and elevation of both FVIII and VWF(FVIII↑/VWF↑). Results The median of VWF was higher in the case group (1521.88 U/L) than in the control group (1281.77U/L)(P=0.023). Compared with patients with both FVIII and VWF within normal range, patients with ele? vation of both FVIII and VWF had more severe neurological dysfunction(NIHSS at admission>5)(OR=3.643,95%CI:1.258~10.549,P=0.017)and poorer prognosis(mRS>2 at the point of 3 months after stroke)(OR=7,95%CI:2.304~21.266,P=0.001), higher proportion of mRS>2 at discharge(OR=3.797,95%CI:1.346~10.713,P=0.012),and more in?patient complications such as infections(OR=3.913,95%CI:1.115~13.729,P=0.033)and neuroworsening(OR=5.538, 95%CI:1.099~27.908,P=0.038). After additional adjustment for various confounding factors, elevation of both FVIII and VWF was an independent predictor of poor prognosis in patients with acute ischemic stroke(OR=4.495,95%CI 1.012~19.957,P=0.048). Conclusions The elevation of FVIII and VWF is positively associated with the severity and prognosis in patients with acute ischemic stroke, which may serve as an independent predictor of poor prognosis.

Objective To identify the routes and branches of the proper plantar digital nerves(PPDN) in the medial of the great toe and its adjoining relationship among the surrounding fascia tissues and organs,which was expected to provide accurate localization of the nerve impingement and possible relevant of anatomical basis for the treatment of nerve entrapment in clinical utility.Methods From December,2016 to January,2019,a total of 54 formalin fixed feet were collected.Fifty of them were performed conventional anatomical procedure,the other 4 were prepared with sectional anatomical technique.The seats and branches of the PPDN in the medial of the great toe were observed;The width and thickness of the nerve were measured at the first metatarpophalangeal joint(FMPJ),along with its proximal and distal sides 0.5 cm.The origin and origin of fascia were observed by foot dissection.Masson staining was used to observe the tissue changes of the nerves in the FMPJ.Results The PPDN of the medial great toe run between the flexor pollicis longus tendon and the abductor pollicis tendon at the proximal,issued (4.21±0.12) final branches.And governed the sensation of the medial half of the great toe.The width of the nerve at the FMPJ was (3.50±0.09) mm,which was significantly increased compared with that of the near [(1.58±0.04) mm] and far [(1.56± 0.03) mm] from the joint.The difference was statistically significant (P＜0.05);The thickness of the nerve in the proximal segment was (0.83±0.04) mm,and that in the distal segment was (0.82±0.03) mm.Compared with that in the FMPJ [(0.67±0.02) mm],the difference was statistically significant (P＜0.05).A deep fascia was observed on the superficial surface of the PPDN at medial great toe,which was stretched between the tendon sheath of the flexor pollicis longus tendon and the tendon of the abductor pollicis muscle.Masson staining showed obvious proliferation of nerve outer mem brane fibers at the metatarpophalangeal joint,the number of nerve fiber bundles increased,and obvious thickening of nerve fiber bundles and nerve fascia.Conclusion Long-term compression can lead to thickening of the epineurium and perineurium,and the superficial fascia is an important factor of thumb pain and numbness caused by the compression of the PPDN at medial of the great toe.

Objective:We performed a Mendelian randomisation (MR) analysis to explore the relationship between serum metabolites and tinnitus.Methods:In this study, 486 serum metabolites were considered as exposure factors, and single nucleotide polymorphisms (SNP) significantly associated with them were used as instrumental variables (IV). The serum metabolite data were obtained from a public database ( http://metabolomips.org/gwas/index.php), while the genome-wide association study (GWAS) summary association statistics for tinnitus were obtained from a Finnish database ( https://r10.finngen.fi/pheno/H8_TINNITUS). The inverse variance weighting (IVW) method was employed as the primary determination method for MR analysis, with corrections for multiple comparisons made using the false discovery rate (FDR). Sensitivity tests were conducted using the MR-Egger regression, Mendelian random polymorphism residuals and outliers (MR-PRESSO) methods. The identified serum metabolites were subjected to chained disequilibrium regression analysis (LDSC) and metabolic pathway analysis. Reverse MR analysis was performed to investigate the possibility of reverse causality. Analyses were performed in R software (version 4.3.1). Results:A total of 17 serum metabolites (including 10 known and 7 unknown metabolites) associated with tinnitus were identified. The known metabolites included protective metabolites such as acetylcarnitine, hydroxyisovaleryl carnitine, glycine, monounsaturated glycerol ester, and glycine-L-valine, and hazardous metabolites such as allantoin, glycerylphosphorylcholine 1-eicosatrienoate, myo-inositol, 15-methylpalmitate, and pseudouridine; the strongest causally protective metabolites were acetylcarnitine, the followed by hydroxyisopentanoyl carnitine and glycine; the hazardous metabolite with the strongest causal effect was pseudouridine, followed by inositol and 15-methylpalmitate; and only hydroxyisopentanoyl carnitine ( PFDR=0.04) and glycerol monooleate ( PFDR=0.04) reached significance values after FDR correction. The findings were free of heterogeneity, pleiotropy and reverse causal associations. The metabolic pathways were mainly enriched in pathways such as ascorbic acid and aldolac metabolism. Conclusions:The study suggests a causal relationship between serum metabolites and tinnitus risk. Serum metabolite levels may influence tinnitus-related metabolic pathways.

Objective: A longitudinal mediating model was designed to explore the relationship between sleep chronotype and depressive mood with stressful life events as the mediating variable, so as to provide reference basis for preventing depression in adolescents. Methods: From March (T1) to October (T2) 2022, the Munich Chronotype Questionnaire, and Adolescent Self-rating Life Events Checklist and Center for Epidemiologic Studies Depression Scale were administered in 1 251 middle school students in the first and second grades of a middle school in Meishan, Sichuan Province for a follow up study. Two wave of date on sleep time type, stressful life events, and depressive moods were collected. Results: At T1, the detection rate of depressive mood was 22.5% in adolescents but 27.0% at T2.At the same time point, there were significant positive correlations between chronotype, stressful life events and depressive mood ( r=0.06-0.69, P <0.05). Cross lagged model results showed that early sleep chronotype could significantly predict later depressive mood ( β=0.53, P <0.05), and early depressive mood could significantly predict later sleep chronotype ( β=0.01, P <0.01). Longitudinal mediation model analysis showed that T1 sleep chronotype not only directly affected T2 depressive mood (direct effect value=1.421, 95% CI =0.985- 1.858 , P <0.01), but also affect T2 depressive mood through the partial mediating effects of T2 stressful life events (indirect effect value=1.268, 95% CI =0.810-1.726, P <0.05). Although T1 depressive mood was a direct predictor of T2 sleep chronotype (direct effect value=0.025, 95% CI =0.017-0.032), it was not a direct predictor of T2 sleep chronotype by partial intermediate action of T2 stressful life events (indirect effect value=-0.001, 95% CI = -0.006- 0.004, P >0.05). Conclusions Sleep chronotype can not only directly predict depressive mood of adolescents, but also indirectly affect depressive mood of adolescents through the longitudinal mediating effect of stressful life events. To prevent depression and improve mental health in this population, adolescents should develop the habit of early sleep schedule, and improve their ability to cope with stressful life events.