OBJECTIVE: This study aimed to investigate the therapeutic effects of Xiaoyao San (XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress (CUMS). METHODS: A total of 24 male SD rats were randomly divided into four groups: control group (C), CUMS control group (M), Venlafaxine positive treatment group (V), and XYS treatment group (X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry (LC-MS) method. TCMSP database and GeneCards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed. RESULTS: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test, and retention time on the rotarod test (P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group (P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group. Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway. CONCLUSION XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.

Objective:To establish the qualitative and quantitative methods of Lomatogonium carinthiacum(Wulf.)Reichb.in the prescription of Mongolian medicine Polypill Zhuanglun-5 decoction,and solve the phe-nomenon of Lomatogonium carinthiacum(Wulf.)Reichb.being replaced.Methods:Microscopic identification method was used to observe the pollen grains in the powder;The reference substance of swertiamarin and Lomato-gonium carinthiacum(Wulf.)Reichb.were used as the control,and the ethyl acetate methanol water formic acid(12∶2∶2∶0.5)was used as the developing agent for TLC identification;HPLC was used under the condin-tion including Agilent Eclipse Plus C18(250 mm × 4.6 mm,5 μm)as chromatographic column and 0.2％phosphoric acid solution(A)-acetonitrile(B)as mobile phase with gradient elution at 238 nm of detection wavelength were used.Contents of Zhuanglun-5 decoction from different manufacturers were determined with swertiamarin as reference substance.Results:Among the 12 batches of Zhuanglun-5 decoction,8 batches were Lomatogonium carinthiacum(Wulf.)Reichb.,2 batches were Viola yedoensis,and 2 batches were other medicinal materials.The content of swertiamarin in 8 batches of Zhuanglun-5 decoction ranged from 0.2 to 11.7 mg·g-1.Conclusion:The established identification method is simple and effective,and the content determination method is stable and has strong specificity.It can provide technical support for the supervision of the preparation,and has a reference effect for the improvement of traditional Chinese and Mongolian pharmaceuti-cal preparation standards.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Objective:To investigate the expression of eukaryotic translation initiation 2α (p-elF2α) and activated translation factor 4 (ATF4) in liver tissues of patients with chronic hepatitis B and their correlation with liver fibrosis.Methods:From Jan.2016 to Jan.2019, 158 cases of chronic hepatitis B patients were enrolled in our hospital. The expression levels of p-elF2α and ATF4 in different stages of liver fibrosis were evaluated by hematoxy-eosin (HE) and immunohistochemical staining, and the correlation was analyzed by Spearman rank correlation.Results:The pathological results of liver specimens showed that there were 19 normal controls (S0), 29 S1, 42 S2, 35 S3 and 33 S4 in each stage of fibrosis. The levels of p-eIF2α and ATF4 in fibrosis group were significantly higher than those in normal control group ( P< 0.001). Additionally, the levels of p-eIF2α and ATF4 in different stages of fibrosis were significantly different. The grade of hepatic fibrosis was positively correlated with the scores of p-eIF2α and ATF4 staining in liver tissues, and the correlation coefficients were 0.473 and 0.422 respectively ( P< 0.05). Conclusions:Hepatic fibrosis in patients with chronic hepatitis B is positively correlated with p-eIF2α and ATF4. p-eIF2α-ATF4 pathway may involve in the process of chronic hepatitis B-induced hepatic fibrosis.

Objective: To evaluate the acute effects of air pollutants (PM2.5,SO2 and NO2) on hospital visits for upper respiratory tract infection in children,and provide the reference for goverment to make effective interventional measures and to instruct prevention and protection of children’s health. Methods: Daily meteorological data, air pollutants levels and hospital visits for upper respiratory tract infection in children between 2016 and 2018 were collected for analysis. The generalized linear model (GLM) based on Quasi-Poisson regression was used for estimating the acute effects of each pollutant on hospital visits for upper respiratory tract infection in children. The confounding factors of seasonal trend, long-term trends, meteorological factors, week effect were controlled in the model. The lag pattern of lag days (lag0-lag5) and moving average effect (lag01-lag05) was conducted. The excessive risk (ER) of hospital visits for upper respiratory tract infection in children with 95% confidence interval (95%CI) was calculated with an increase of 10 μg/m3 of PM2.5，SO2 and NO2 respectively. Results: Seasonality was showed in the daily pollutants and hospital visits for upper respiratory tract infection in children from 2016 and 2018 in Xining. The average of annual PM2.5，SO2 and NO2 concentration were (47±28)(15+9)(35±17) μg/m3 respectively. The average number of hospital visits for upper respiratory tract infection in children was seventytwo persons. With an increase of 10 μg/m3 of PM2.5,SO2 and NO2 hospital visits for upper respiratory tract infection in children increased by 0.78% (95%C=0.39%-1.17%), 4.19% (95%CI=3.05%-5.34%) and 1.93% (95%CI=1.15%-2.71%) respectively. The three kinds of air pollutants all had certain lag effect. Conclusion The main air pollutants PM2.5，SO2 and NO2, have acute effects on hospital visits for upper respiratory tract infection in children in Xining district,thus,the work of preventing and controlling air pollution need to be furthur strengthened.

Aim To explore the effect of activated SK channels(small conductance Ca2+-activated K+ channels) on morphine-induced hyperalgesia in the spinal cord in mice.Methods Adult C57BL6/N male mice were chosen to establish the model of morphine-hyperalgesia.The changes of tail withdrawal latency(TWL), mechanical withdrawal threshold(MWT) and the threshold of visceral pain were observed after intrathecal 1-EBIO, the agonist of SK channels.Results Compared with the control group, TWL, MWT and the threshold of visceral pain were decreased after morphine injection.After intrathecal 1-EBIO, the TWL, MWT and visceral pain threshold were increased.The level of spinal membrane SK2 expression in morphine-treated mice was decreased compared with that of control group.After intrathecal 1-EBIO, the level of spinal membrane SK2 expression was increased.Conclusion SK channels in the spinal cord are involved in morphine-induced hyperalgesia in mice.

With the growing awearness of Big data and its application in economic,social and scientific fields,this paper analyzed the impact and challenges big data has brought to the field of biomedical research,and put forward suggestion of improving applications of big data in biomedical research.

The primary transitional cell carcinoma in nasal cavity is clinically manifested by progessively increasing nasal decongestion,bloody and purulent secretion intermittent appear ,headaches,hearing loss.The macroscopic character showed that a medium gray red ground tissue .The tumor cells were arranged in nested ,pa-pillary by microscopy,the nucleus was round or oval shape ,the tumor cells was infiltrating growth,basophilia or bright.Immunhistochenmical showed that P63,CK5/6,CK18,UroplakinIII,CerbB -2,CEA were positive,Ki67 positive index was about S -100,Cga,Syn,Calponinare all tested negative .Nasal primary transitional cell carcino-ma is uncommon clinically ,and it is easy to misdiagnosed .Its diagnosis and differential diagnosis mainly depends on pathological histoloy and immunohistochenmical examination .

The role of Military Medical University featuring both battlefield and market service determines the necessity to seek balance between military and civilian planning for scientific and technological innovation.In the management of scientific and technological achievements,Third Military Medical University sticks to the development mode of military-civil integration.First,it establishes the management concept suit for its roles and characteristics,organizational strategy,policy and system.Secondly,it implements transitional development.Thirdly,it serves social development and military medical services.As a result,a series of outstanding scientific and technological achievements have been obtained,and remarkable progress and results have been achieved.