Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Objective:To analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective: To observe the efficacy of unblocking and regulating the Belt Vessel acupuncture method for patients with abdominal obesity in Germany and its influence on the body fat parameters and glycolipids metabolism. Methods: A total of 82 cases of abdominal obesity in Germany were selected. There were two dropout cases in the treatment process. All of the patients received acupuncture at Daimai (GB26), Daheng (SP15), Tianshu (ST25), Zhongwan (CV12), Shuidao (ST28), Waiguan (TE5), and Zulinqi (GB41). The patients received acupuncture therapy once every 2-3 d, 3 times a week. The treatment duration lasted 4 weeks. Before and after treatment, the body mass (BM), waist circumference (WC), abdominal circumference (AC), hip circumference (HC), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (GLU) were measured respectively, and the body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body fat rate (BFR) were calculated. Results: After treatment, the total effective rate was 72.5％; the levels of BM, WC, AC, HC, BMI, WHR, WHtR, BFR, TC, LDL-C, and GLU declined significantly compared with those before treatment (P<0.01), while the TG and HDL-C slightly declined, but the differences were statistically insignificant (P>0.05). Conclusion: The unblocking and regulating the Belt Vessel acupuncture method can significantly reduce body fat parameters such as BM, AC, and BFR, and correct the disorders of glucose and lipid metabolism in patients with abdominal obesity in Germany.

Objective:To investigate the influence and mechanism of stromal interaction molecule 1 (STIM1) in microglia/macrophages M1 activation after cerebral ischemia-reperfusion injury.Methods:(1) Animal experiment: 20 male C57BL/6J mice were randomly divided into sham-operated (Sham) group, middle cerebral artery occlusion and reperfusion (MCAO/R) group, MCAO/R+si-Ctrl group, and MCAO/R+si-STIM1 group ( n=5); MCAO/R models were established in mice of the latter 3 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the MCAO/R+si-Ctrl group and MCAO/R+si-STIM1 group. The transfection efficiency of STIM1 and the expression of microglia/macrophages M1 activation marker cluster of differentiation 86 (CD86) in each group were observed. (2) Cell experiment: primary microglia were divided into Ctrl group, oxygen-glucose deprivation/re-oxygenation (OGD/R) group, OGD/R+si-Ctrl group, OGD/R+si-STIM1 group, OGD/R+solvent group, and OGD/R+4-phenylbutyric acid (4-PBA) group; OGD/R models were established in the later 5 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the OGD/R+si-Ctrl group and OGD/R+si-STIM1 group; cells in the OGD/R+4-PBA group were pre-treated with 1 mmol/L 4-PBA for 1 h at 24 h before OGD/R modelling to inhibit endoplasmic reticulum stress (ERS), and cells in the OGD/R+solvent group were pre-treated with 0.5% dimethyl sulfoxide (DMSO) for 1 h at the same time. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), ELISA, Western blotting and other methods were used to detect the levels of CD86, tumour necrosis factor-α ( TNF-α) mRNA, interleukin (IL)-1β, and ERS-related proteins (transcription factor C/EBP homologous protein [CHOP], activated transcription factor 4 [ATF4]) in these cells. Results:(1) Animal experiment: the STIM1 expression in MCAO/R+si-STIM1 group was significantly lower than that in Sham group, MACO/R group and MCAO/R+si-Ctrl group ( P<0.05); as compared with that in the MACO/R group and MCAO/R+si-Ctrl group, the number of microglia/macrophages co-expressing CD86 and Iba-1 around the ischemic foci of mice in the MCAO/R+si-STIM1 group was significantly decreased ( P<0.05). (2) Cell experiment: as compared with those in the OGD/R group and OGD/R+si-Ctrl group, the expression levels of STIM1, CD86, and TNF-α mRNA, and supernatant IL-1β content in the OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+si-CTRL group, the ATF4 and CHOP expression levels in OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+solvent group, the CD86 level, TNF-α mRNA expression level and IL-1β content in the OGD/R+4-PBA group were significantly decreased ( P<0.05). Conclusion:STIM1 affects microglia/macrophages M1 activation after ischemia-reperfusion injury by regulating ERS level.

Objective:To investigate the manifestations of liver injury in hospitalized patients with coronavirus disease 2019 (COVID-19), to investigate the prognosis indicators of the disease, and to provide the reference for clinical diagnosis and treatment.Methods:From January 10 to February 14, 2020, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, the data of 333 hospitalized patients with COVID-19 were collected. The changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil) and albumin of the first liver function test after admission and the reexaminations of liver function test during hospitalization period in patients with liver injury were retrospectively analyzed. Student t test and Chi-square test were used for statistical analysis. Results:Liver injury occurred in 39.6% (132/333) of COVID-19 patients. There was no statistically significant difference in the rate of liver injury between patients in intensive care unit (ICU) and in general ward (45.6%, 26/57 vs. 38.4%, 106/276; χ2=1.026, P>0.05). 67.4% (89/132) of COVID-19 patients with liver injury presented with increased ALT or AST level on admission. During hospitalization, the level of ALT was higher than that of the first examination after admission ((60.28±50.44) U/L vs. (42.25±32.21) U/L), and the difference was statistically significant ( t=-3.230, P<0.05). The levels of ALT and AST of 71.2% (94/132) patients were both <80 U/L, which indicated that most of the patients showed mild liver injury. The patients with elevated level of TBil, DBil and IBil accounted for 3.9% (13/333), 5.4% (18/333) and 2.4% (8/333) of the COVID-19 patients, respectively. The albumin level of COVID-19 patients with liver injury during hospitalization was lower than that of the first examination after admission ((31.8±5.1) g/L vs. (33.7±5.4) g/L), and the difference was statistically significant ( t=2.712, P<0.05). The albumin levels at first examination on admission and reexamination during hospitalization of patients in ICU were both significantly lower than those of patients in general ward ((29.3±3.7) g/L vs. (34.8±5.1) g/L and (27.6±2.8) g/L vs. (32.9±5.1) g/L), and the differences were statistically significant ( t=4.928 and 4.783, both P<0.05). Conclusions:The incidence of liver injury in COVID-19 patients is high. A slight increase in aminotransferase levels is particularly common. Bilirubin abnormality is relatively rare and mild. The level of albumin may be one of the indicators for the severity and prognosis of COVID-19.

Objective To teach neurosurgical residents of standardized training by using teaching method with multi-modality visualization and to explore its application effects.Methods Total 122 students were randomly divided into two groups:multi-modality visualization teaching group (n=61) and traditional teaching group (n=61).The evaluation of teaching effect was conducted by questionnaire of students and the analysis of test scores after the course.Comparison between the two groups was made by using independent sample t test.Results Questionnaire showed that the satisfaction of teaching mode (88.5％),learning efficiency (93.4％),and training results (90.1％) with multi-modality visualization teaching group were statistically higher than traditional group (P＜0.05).Test score showed that results of theory test (88.5 ± 5.1),on-spot examination (91.6 ± 5.5),and overall score (89.3 ± 5.2) were also statistically higher in multi-modality visualization teaching group than that of control group (P＜0.05).There was no significant difference in clinical skills assessment between two groups.Conclusions Teaching with multi-modality visualization can significantly improve the efficiency of neurosurgical clinical teaching and promote the training effect of students,which provides a new strategy of neurosurgical clinical teaching.

OBJECTIVE： To analyze the difference of volatile oil components from the leaves of Clausena lansium and Clausena excavata. METHODS： The volatile oil was extracted from the leaves of C. lansium and C. excavata by steam distillation. GC-MS method was adopted to analyze volatile oil to obtain TIC. After mass spectra scanning of the chromatographic peaks in the TIC diagram by HPMSD chemical workstation， chemical components of volatile oil in 2 kinds of samples were identified by retrieving and comparing mass spectrum database NIST Version 1.7. The peak area normalization method was used to calculate the relative mass fraction of each component. RESULTS： A total of 43 and 31 kinds of components were identified in volatile oil from the leaves of C. lansium and C. excavata； total relative mass fractions were 97.59％ and 98.57％. Relative mass fractions of 19 and 18 components in volatile oil from the leaves of C. lansium and C. excavata were more than 1％， mainly being sesquiterpenoids. Relative mass fractions of 7 and 5 components in volatile oil from the leaves of C. lansium and C. excavata were more than 5％； the volatile components in volatile oil from the leaves of C. lansium were mainly （-）-spatol （12.35％） and （E）-5-{（1R，3R，6S）-2，3-dimethyltricyclic [2.2.1.02，6] heptane-3-yl}-2-methyl pentane-2-enol （14.70％）； those from the leaves of C. excavata were mainly （E）-sesquihydrated betuline （24.94％） and 1-（1， 5-dimethy-4-hexenyl）-4-methyl-benzene （16.15％）. A total of 4 components were found in volatile oil from the leaves of C. lansium and C. excavata， mainly being α-humulene， （E）-5-{（1R，3R，6S）-2，3-dimethyltricyclic [2.2.1.02，6] heptane-3-yl}-2-methylpentaeryl-2-enol， caryophyllene oxide and （-）-spatol； the content differences of them were not significant. CONCLUSIONS： The components of volatile oils from the leaves of C. lansium and C. excavata are basically similar However， the composition and comtent of specific components are quiet different and can not substituted for each other.

OBJECTIVE： To isolate and identify the coumarins from the seeds of Clausena lansium， and to study their inhibitory activity of α-glucosidase and nematicidal activity against Panagrellus redivivus. METHODS： Column chromatography， reversed phase silica gel column chromatography and HPLC method were used to separate and purify the coumarins from the seeds of C. lansium. The structures of compounds were identified according to physicochemical properties， 1H-NMR and 13C-NMR spectral data. Using acarbose and avermectin as positive control， PNPG and Berman funnel methods were used to investigate the α-glucosidase inhibitory activity and nematicidal activity against P. redivivus， respectively. RESULTS： Seven coumarins compounds were isolated from the seeds of C. lansium， and were identified as 7-hydroxy-1-benzopiran-2-one （Ⅰ）， Wampetin （Ⅱ）， Lansiumarin-C （Ⅲ）， Claucoumarin A （Ⅳ）， Clausenalansimin A （Ⅴ）， （E，E）-8-（7-hydroxy-3，7-dimethylocta-2，5-dienyloxy） psoralen （Ⅵ）， Dihydroindicolactone （Ⅶ）. Under 0.25 mg/mL， the α-glucosidase inhibitory rates of compounds Ⅰ， Ⅲ， Ⅴ were （32.4±1.9）％，（37.1±6.0）％， （39.5±1.1）％， respectively. Under 2.5 mg/mL， corrected mortality of compounds Ⅰ， Ⅳwere 50.5％ and 47.9％. CONCLUSIONS： Compounds Ⅰ， Ⅲ， Ⅴ show α-glucosidase inhibitory activity， and compounds Ⅰ，Ⅳ display nematicidal activity against P. redivivus.  α-Glucosidase inhibitory activity of compounds Ⅲ， Ⅴ， and nematicidal activity of compound Ⅳ are found for the first time.

Objective:To study the astragalus polysaccharides ( APS) effect on immune induced by influenza A virus HA2 eu-karyotic expression vector.Methods: The HA2 encoded by the DNA vaccine vector was efficiently expressed in CHO cells, as determined by reverse transcription polymerase chain reaction ( RT-PCR) and fluorescence analysis.60 rats were divided into six groups randomly,which were immunized with normal saline,pEGFP-N1,pHA2/EGFP+different dose of APS by intramuscular injection.The control sera were collected before injection.After injected the 36th day, sera were collected to analyzing IFN-γ, IL-4 and IgG level.Results:IFN-γ,IL-4 and IgG level of pHA2/EGFP+mAPS group was different from that of pEGFP-N1 group or pHA2/EGFP+lAPS group( P<0.05 ).Conclusion: Middle dose of APS could increase immune induced by influenza A virus HA2 eukaryotic expression vector.