Objective:To explore the mechanism through which the Ginkgo biloba extract(EGb)ameliorates depres-sion-like behaviors in chronic copper-exposed mice.Methods:A mouse model with depression was induced by chronic oral administration of copper sulfate solution(200 mg/L),followed by oral administration of the EGb(120 mg/L)for one month.Elevated plus-maze test,forced swimming test,and sucrose preference test were employed to detect the de-pression-like behaviors of mice.TUNEL staining was utilized to examine apoptosis in the hippocampal region of mice.Immunohistochemistry was adopted to detect the in situ expression of pro-brain-derived neurotrophic factor(proBDNF)and brain-derived neurotrophic factor(BDNF)in the hippocampal region.RT-qPCR was used to measure the expression of the BDNF mRNA.Western blot was utilized to determine the expressions of proteins such as proBDNF,mature BDNF(mBDNF),cAMP response element binding protein(CREB),phospho-CREB(p-CREB),tyrosine kinase receptor B(TrkB),p75 neurotrophin Receptor(p75NTR),furin,proprotein convertase subtilisin/kexin type 1(PCSK1),and matrix metalloproteinase-9(MMP9).Results:Chronic copper exposure led to depression-like behaviors in mice,in-creased neuronal apoptosis in the hippocampal region,enhanced proBDNF expression and reduced mBDNF expression(P＜0.05),decreased the expression of the downstream receptor protein TrkB and increased the expression of p75NTR(P＜0.05),and decreased the level of CREB and p-CREB(P＜0.05).Meanwhile,the expressions of intracellular proteases furin and PCSK1 in the hippocampal region of mice with depression-like behaviors decreased(P＜0.05),while the expression of extracellular protease MMP9 increased(P＜0.05).EGb was capable of alleviating depression-like behaviors and neuronal apoptosis in mice and partially reversing the abnormal expressions of BDNF,proBDNF,TrkB,p75NTR,CREB,p-CREB,furin,and PCSK1 proteins caused by copper exposure.Conclusion:Chronic copper exposure can lead to depression-like behaviors and apoptosis in mice.EGb can reverse these manifestations and corre-late with the balance of proBDNF/BDNF in the hippocampal region,which may offer novel insights for the treatment of depression.

Objective:To explore the mechanism through which the Ginkgo biloba extract(EGb)ameliorates depres-sion-like behaviors in chronic copper-exposed mice.Methods:A mouse model with depression was induced by chronic oral administration of copper sulfate solution(200 mg/L),followed by oral administration of the EGb(120 mg/L)for one month.Elevated plus-maze test,forced swimming test,and sucrose preference test were employed to detect the de-pression-like behaviors of mice.TUNEL staining was utilized to examine apoptosis in the hippocampal region of mice.Immunohistochemistry was adopted to detect the in situ expression of pro-brain-derived neurotrophic factor(proBDNF)and brain-derived neurotrophic factor(BDNF)in the hippocampal region.RT-qPCR was used to measure the expression of the BDNF mRNA.Western blot was utilized to determine the expressions of proteins such as proBDNF,mature BDNF(mBDNF),cAMP response element binding protein(CREB),phospho-CREB(p-CREB),tyrosine kinase receptor B(TrkB),p75 neurotrophin Receptor(p75NTR),furin,proprotein convertase subtilisin/kexin type 1(PCSK1),and matrix metalloproteinase-9(MMP9).Results:Chronic copper exposure led to depression-like behaviors in mice,in-creased neuronal apoptosis in the hippocampal region,enhanced proBDNF expression and reduced mBDNF expression(P＜0.05),decreased the expression of the downstream receptor protein TrkB and increased the expression of p75NTR(P＜0.05),and decreased the level of CREB and p-CREB(P＜0.05).Meanwhile,the expressions of intracellular proteases furin and PCSK1 in the hippocampal region of mice with depression-like behaviors decreased(P＜0.05),while the expression of extracellular protease MMP9 increased(P＜0.05).EGb was capable of alleviating depression-like behaviors and neuronal apoptosis in mice and partially reversing the abnormal expressions of BDNF,proBDNF,TrkB,p75NTR,CREB,p-CREB,furin,and PCSK1 proteins caused by copper exposure.Conclusion:Chronic copper exposure can lead to depression-like behaviors and apoptosis in mice.EGb can reverse these manifestations and corre-late with the balance of proBDNF/BDNF in the hippocampal region,which may offer novel insights for the treatment of depression.

Objective:To analyze the disease burden of Parkinson's disease (PD) in China from 1990 to 2021 and predict the disease burden of PD from 2022 to 2030.Methods:Based on the data of PD incidence in China from the Global Burden of Disease Study 2021 (GBD 2021), changes in PD disease burden from 1990 to 2021 were analyzed. Age-period-cohort model was used to analyze the independent influences of age, period and cohort in PD incidence (according to age group of 5 years, patients were divided into 15 groups: group of 20-24 years, group of 25-29 years..., and group of 90-94 years; according to a 5-year period, patients were divided into 6 groups: group of 1992-1996, group of 1997-2001..., and group of 2017-2021; because of birth cohort=period-age, patients were divided into 20 birth cohorts: birth cohort of 1897-1906, birth cohort of 1902-1911..., and birth cohort of 1992-2001). Nordpred model was used to predict the disease burden of PD from 2022 to 2030.Results:(1) From 1990 to 2021, number of PD patients, and PD incidence and standardized incidence in China showed upward trends. The standardized incidence increased by 89.68% for the total population, 89.71% for males, and 77.64% for females. (2) PD incidence was low in young subjects and increased obviously in subjects aged 60 years. PD incidence in subjects aged 20-24 years or 90-94 years was 0.07/100 000 and 643.31/100 000, respectively. Compared with female subjects, male subjects aged 60-94 years had higher PD incidence. (3) The onset relative risk increased from 0.71 (95% CI: 0.69-0.73) in group of 1992-1996 to 1.17 (95% CI: 1.16-1.19) in group of 2017-2021 in the total population, increased from 0.68 (95% CI: 0.66-0.70) to 1.18 (95% CI: 1.16-1.21) in males, and increased from 0.75 (95% CI: 0.73-0.77) to 1.14 (95% CI: 1.12-1.16) in females. (4) Onset relative risk was 0.40 (95% CI: 0.33-0.48) in the earliest birth cohort (1897-1906), which increased to 1.81 (95% CI: 0.95-3.43) in the latest birth cohort (1992-2001). (5) Number of PD patients in males, females and total population in China would increase to 455 010, 301 173 and 756 183, respectively, and the standardized incidence would increase to 56.45/100 000, 32.28/100 000 and 43.40/100 000, respectively, till 2030. Conclusion:PD disease burden in China from 1990 to 2021 is severe, particularly among males and the elderly; the disease burden is projected to continue rising up till 2030.

Objective:To analyze the disease burden of Parkinson's disease (PD) in China from 1990 to 2021 and predict the disease burden of PD from 2022 to 2030.Methods:Based on the data of PD incidence in China from the Global Burden of Disease Study 2021 (GBD 2021), changes in PD disease burden from 1990 to 2021 were analyzed. Age-period-cohort model was used to analyze the independent influences of age, period and cohort in PD incidence (according to age group of 5 years, patients were divided into 15 groups: group of 20-24 years, group of 25-29 years..., and group of 90-94 years; according to a 5-year period, patients were divided into 6 groups: group of 1992-1996, group of 1997-2001..., and group of 2017-2021; because of birth cohort=period-age, patients were divided into 20 birth cohorts: birth cohort of 1897-1906, birth cohort of 1902-1911..., and birth cohort of 1992-2001). Nordpred model was used to predict the disease burden of PD from 2022 to 2030.Results:(1) From 1990 to 2021, number of PD patients, and PD incidence and standardized incidence in China showed upward trends. The standardized incidence increased by 89.68% for the total population, 89.71% for males, and 77.64% for females. (2) PD incidence was low in young subjects and increased obviously in subjects aged 60 years. PD incidence in subjects aged 20-24 years or 90-94 years was 0.07/100 000 and 643.31/100 000, respectively. Compared with female subjects, male subjects aged 60-94 years had higher PD incidence. (3) The onset relative risk increased from 0.71 (95% CI: 0.69-0.73) in group of 1992-1996 to 1.17 (95% CI: 1.16-1.19) in group of 2017-2021 in the total population, increased from 0.68 (95% CI: 0.66-0.70) to 1.18 (95% CI: 1.16-1.21) in males, and increased from 0.75 (95% CI: 0.73-0.77) to 1.14 (95% CI: 1.12-1.16) in females. (4) Onset relative risk was 0.40 (95% CI: 0.33-0.48) in the earliest birth cohort (1897-1906), which increased to 1.81 (95% CI: 0.95-3.43) in the latest birth cohort (1992-2001). (5) Number of PD patients in males, females and total population in China would increase to 455 010, 301 173 and 756 183, respectively, and the standardized incidence would increase to 56.45/100 000, 32.28/100 000 and 43.40/100 000, respectively, till 2030. Conclusion:PD disease burden in China from 1990 to 2021 is severe, particularly among males and the elderly; the disease burden is projected to continue rising up till 2030.

Objective     To investigate the safety of thoracic surgery for high-altitude patients in local medical center. Methods    We retrospectively collected 258 high-altitude patients who received thoracic surgery in West China Hospital, Sichuan University (plain medical center, 54 patients) and People's Hospital of Ganzi Tibetan Autonomous Prefecture (high-altitude medical center, 204 patients) from January 2013 to July 2019. There were 175 males and 83 females with an average age of 43.0±16.8 years. Perioperative indicators, postoperative complications and related risk factors of patients were analyzed. Results    The rate of minimally invasive surgery in the high-altitude medical center was statistically lower than that in the plain medical center (11.8% vs. 55.6%, P<0.001). The surgical proportions of tuberculous empyema (41.2% vs. 1.9%, P<0.001) and pulmonary hydatid (15.2% vs. 0.0%, P=0.002) in the high-altitude medical center were statistically higher than those in the plain medical center. There was no statistical difference in perioperative mortality (0.5% vs. 1.9%, P=0.379) or complication rate within 30 days after operation (7.4% vs. 11.1%, P=0.402) between the high-altitude center and the plain medical center. Univariate and multivariate analyses showed that body mass index≥ 25 kg/m2 (OR=8.647, P<0.001) and esophageal rupture/perforation were independent risk factors for the occurrence of postoperative complications (OR=15.720, P<0.001). Conclusion    Thoracic surgery in the high-altitude medical center is safe and feasible.

Objective:To study the learning curve in laparoscopic left lateral hepatic sectionectomy.Methods:The clinical data of 62 consecutive patients who underwent left lateral hepatic sectionectomy by a single operator from February 2015 to May 2022 in General Hospital of Northern Theater Command were retrospectively analyzed. There were 22 males and 40 females, with mean ±s.d. of (50.7±11.7) years. The learning curve was depicted and evaluated by using the cumulative summation test. The general information, operation and postoperative indicators of the growth level group and the master level group were compared.Results:The average operation time of the 62 consecutive subjects was (172.9±70.1) minutes. Intraoperative blood loss was 100 (50, 200) ml. Two patients were converted to open hepatectomy. Clavien-Dindo grade I postoperative complications occurred in 20 patients (32.3%), with grade Ⅱ in 1 patient (1.6%) and grade Ⅲb in another patient (1.6%). The learning curve reached its highest point on the 20th patient by using the cumulative summation test. The study subjects were then assigned into the growth level group (patient 1-20) and the master level group (patient 21-62). The master level group had a significantly wider spread of patient age [(52.9±11.0) years vs (46.1±11.9) years], decreased operation time [(146.8±55.6) min vs (227.9±66.7) min], shortened drainage tube removal time [4(3, 5) d vs 6(4, 7) d] and decreased postoperative hospital stay [5(5, 7) d vs 6.5(4, 9) d] (all P<0.05) when compared with the growth level group. Conclusion:Left lateral hepatic sectionectomy was safe and feasible, and a single operator went through a learning curve of 20 patients before he/she could master the operation more proficiently.

Objective:To study the features of adenomyomatous hyperplasia (AH) of the Vaterian system (common bile duct and ampulla of Vater) to help in the diagnosis and management of this disease.Methods:A retrospective analysis on the data of 17 patients who had a postoperative pathological diagnosis of AH of the Vaterian system treated from January 2005 to December 2021 at the First Medical Center of the PLA General Hospital was carried out with 12 males and 5 females, aged (58.4±11.3) years. The clinical presentations, treatment and postoperative pathology of these patients were analyzed. Patients with dysplasia of the tubular mucosal epithelium in the non-cancerous area around the AH under microscopy were included in the AH with dysplasia group ( n=8), and those without dysplasia were included in the control group ( n=9). The clinical characteristics of the two groups were compared. Results:The main clinical symptoms were abdominal pain in 8 patients, jaundice in 7 patients and fever in 2 patients. Preoperative imaging showed 10 cases of occupying lesions and 6 cases of abnormally dilated intrahepatic and extrahepatic bile ducts without obvious lesions or stones or biliary tract injury stenosis. Sixteen patients underwent radical pancreaticoduodenectomy, and 1 patient underwent extrahepatic biliary resection combined with choledochojejunostomy for bile duct obstruction due to biliary stones, 3 patients had combined malignant tumors, 1 patient had a carcinoma of AH origin at the ampulla of Vater, and the other 2 patients had neoplastic lesions in the mucosal epithelium adjacent to the AH (cholangiocarcinoma and ampullary carcinoma, respectively). There were no significant differences in age, gender, bile duct stones, cholangitis, combined carcinoma and liver function indexes between the two groups of patients with AH of the Vaterian system (all P>0.05). Conclusion:Adenomyomatous hyperplasia of the Vaterian system was difficult to distinguish preoperatively from malignant tumors basing on its clinical presentations or imaging findings. Such patients are recommended to be treated surgically.

Objective:To investigate the susceptibility and incidence of seasickness in navy pilots who had been deployed on ships and its influence on their onboard life and flight operation capability，so as to provide reference for ensuring the flight safety of navy pilots.Methods:A total of 41 navy pilots were surveyed by a questionnaire on body mass index（BMI），results of fitness test，smoking history，seasickness sensitivity of parents，personal seasickness susceptibility index，symptoms and severity of seasickness，and how and to what extent the seasickness had affected their living and training.Results:（1）During the navigations，the incidence of seasickness was 61.90%-71.79%，and 71.43%-87.18% of the pilots felt it had affected their life and flight operation capability. The severity of seasickness was significantly correlated with the severity of its influence on flight operation capability（ P<0.01）；（2）Seasickness affected not only pilots’ onboard life，such as appetite，fitness，attention，sleep，and onboard activity（20.00%-86.67%），but also their flight operation capability（14.71%-26.67%）；（3）The incidence of seasickness was significantly correlated with personal seasickness susceptibility index（ P<0.05），but it had no correlation with BMI，fitness，smoking history，or seasickness sensitivity of parents（ P>0.05）. Conclusion:There is close correlation between pilots’ seasickness severity and their flight operation capability. Therefore，pilots should be screened and trained before undertaking onboard missions.

Objective:To investigate the susceptibility and incidence of seasickness in navy pilots who had been deployed on ships and its influence on their onboard life and flight operation capability，so as to provide reference for ensuring the flight safety of navy pilots.Methods:A total of 41 navy pilots were surveyed by a questionnaire on body mass index（BMI），results of fitness test，smoking history，seasickness sensitivity of parents，personal seasickness susceptibility index，symptoms and severity of seasickness，and how and to what extent the seasickness had affected their living and training.Results:（1）During the navigations，the incidence of seasickness was 61.90%-71.79%，and 71.43%-87.18% of the pilots felt it had affected their life and flight operation capability. The severity of seasickness was significantly correlated with the severity of its influence on flight operation capability（ P<0.01）；（2）Seasickness affected not only pilots’ onboard life，such as appetite，fitness，attention，sleep，and onboard activity（20.00%-86.67%），but also their flight operation capability（14.71%-26.67%）；（3）The incidence of seasickness was significantly correlated with personal seasickness susceptibility index（ P<0.05），but it had no correlation with BMI，fitness，smoking history，or seasickness sensitivity of parents（ P>0.05）. Conclusion:There is close correlation between pilots’ seasickness severity and their flight operation capability. Therefore，pilots should be screened and trained before undertaking onboard missions.

OBJECTIVE：To develop a metho d for determining the plasma concentration of sulfasalazine （SSZ）metabolite sulfapyridine（SP）in rats ，and to investigate the effects of esomeprazole （ESOM）on the pharmacokinetic behavior of SSZ in rats. METHODS：Male SD rats were randomly divided into SSZ group and SSZ+ESOM group ，with 6 rats in each group. SSZ+ESOM group were given Esomeprazole enteric-coated tablets [ 90 mg/（kg·d）] intragastrically for 14 days. On the 15th day ，the rats in 2 groups were given Sulfasalazine enteric coated tablets （90 mg/kg）intragastrically，and blood sample was collected from the inner canthus at 0.5，1，1.5，2，3，4，6，8，10，12，24，36，48，72 h after administration. After protein precipitation with methanol ， using diazepam as internal standard ，Agilent XDR-C 18 column was adopted with methanol- 0.1％ formic acid solution （gradient elution）as mobile phase. The concentration of SSZ metabolite SP in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by using DAS 3.0.1 software and compared between 2 groups. RESULTS ：The linear range of SP were 2-1 000 ng/mL. The methodology met the requirements of Chinese Pharmacopeia . There was no statistical significance in pharmacokinetic parameters of SP between 2 groups，such as AUC 0－t，tmax，t1/2z，cmax，MRT0－t（P＞0.05）. CONCLUSIONS ：The established method is simple ，rapid and sensitive ；it can be used for the concentration determination of SSZ metabolite SP in plasma. ESOM has no significant effect on the pharmacokinetic behavior of SSZ in rats.