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 relationships of pre-radiotherapy body weight,gender,age,EBVDNA,hemoglobin,plasma albumin,and induction chemotherapy regimen with the changes of target area and lymph node volume in adaptive radiotherapy,so as to provide a reference for the timing and population selection of adaptive radiotherapy.Methods A retrospective analysis was conducted on 34 patients who received the first course of radiotherapy at Sun Yat-sen University Cancer Center from January 2022 to November 2022.All patients underwent CT scans again after 20 sessions of radiotherapy for developing the secondary radiotherapy plans.The body weight,gender,age,tumor stage,hemoglobin,plasma albumin,induction chemotherapy regimen,and EBVDNA were collected.Results The tumor volume reduction in the primary focus was more evident in patients with pre-treatment plasma albumin≥40 g/L than in those with pre-treatment plasma albumin<40 g/L(t=3.971,P=0.001),and in patients with pretreatment EBVDNA≤4000 copies/mL than in those with pretreatment EBVDNA>4000 copies/mL(t=4.080,P=0.001).Pearson analysis showed that GTVnx volume difference was positively correlated with pre-radiotherapy GTVnx volume(r=0.444,P=0.009),right parotid gland volume difference(r=0.737,P<0.001),left parotid gland volume difference(r=0.435,P=0.010),and hemoglobin(r=0.722,P<0.001).Conclusion The reduction in tumor volume during radiotherapy is more pronounced in nasopharyngeal cancer patients with normal plasma albumin level and those with pretreatment EBVDNA≤4000 copies/mL.The pre-radiotherapy treatment volume of primary focus,parotid gland volume change before and after radiotherapy,and pre-radiotherapy EBVDNA,hemoglobin and plasma albumin levels can be used to predict the degree of tumor volume shrinkage during radiotherapy,providing a reference for the selection of the timing of adaptive radiotherapy for nasopharyngeal carcinoma.

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 analyze the situation of AIDS knowledge and discrimination among freshmen in Chengdu city, and to explore possible effects of AIDS knowledge on discrimination. Methods: A cluster random sampling was employed to investigate 1 053 college students from 11 universities in Chengdu about their HIV/AIDS knowledge and discrimination. The scores of AIDS knowledge and discrimination of students with different characteristics were analyzed, and the influence path of AIDS knowledge on AIDS discrimination were further analyzed based on different peer relationships. Results: The total scores of AIDS knowledge was negatively correlated to AIDS discrimination( r s =-0.13, P <0.01). After adjusting for confounding factors, the total score of AIDS knowledge was associated with the total score of AIDS discrimination( β =-0.12, P <0.01). AIDS knowledge played a role in AIDS discrimination in intimate, general and unfamiliar peer relationships, with standardized path coefficients of -0.20, -0.24 and -0.18 respectively( P <0.01). Conclusion AIDS knowledge are correlated with discrimination among freshmen under different peer relationships. More anti-AIDS discrimination courses should be added to AIDS education to reduce the students’ fear and stigma of HIV/AIDS patients and related risk groups.

Objective:To find out the obstacle factors in its clinical application according to the clinical situation of the application of urinary catheter fixation device.Methods:From September 2018 to October 2018, 19 nurses working in the urology ward of Peking University First Hospital were selected for a semi-structured interview. Based on the theoretical domain framework, the interview outline was formulated and the content was analyzed, and the topic was extracted again.Results:This study identified obstacle factors related to 5 areas of the theoretical domain framework, namely "knowledge, social or professional role and identity, motivation and goals, environmental factors and social influence". The themes were extracted again, respectively: "the system level of evidence implementation (organizational factors, training, product categories) needs to be optimized, the level of willingness of users (patients) for evidence implementation needs to be improved and the sustainability of evidence application needs to be strengthened".Conclusions:The factors that affect the clinical application of urinary catheter fixation devices are multiple, and future research needs to formulate targeted intervention plans based on evidence according to obstacles identified.

OBJECTIVE： To investigate the effects of Lindera aggregate of stir-baking with vinegar-Aucklandia lappa on gastric emptying and gastrointestinal hormones in functional dyspepsia liver depression and qi stagnation （FDLDQS） model rats. METHODS： Totally 60 SD rats were randomly divided into blank group （n＝10） and modeling group （n＝50）； FDLDQS model was induced by chronic stress restraint or food deprivation or excessive fatigue in modeling group. After modeling， model rats were randomly divided into model group （normal saline）， L. aggregate of stir-baking with vinegar group （1.62 g/kg， calculated by crude drug）， A. lappa group （1.62 g/kg， calculated by crude drug）， L. aggregate of stir-baking with vinegar-A. lappa group （1 ∶ 1， m/m，1.62 g/kg， calculated by crude drug） and mosapride group （positive control， 1.35 mg/kg）， with 10 rats in each group. Administration groups were given relevant medicine intragastrically once a day； blank group and model group were given constant volume of normal saline intragastrically， for consecutive 14 d. 2 h after last medication， gastric emptying rate and small intestinal propulsion rate of rats in each group were measured by phenol red content method. After HE staining， the morphological changes of antrum tissue were observed under microscope. The contents of motilin （MTL）， gastrin （GAS） and cholecystokinin （CCK） in serum were determined by ELISA method. RESULTS： Compared with blank group， gastric emptying rate and small intestinal propulsion rate of rats were decreased significantly in model group （P＜0.01）； the serum contents of MTL and GAS were decreased significantly （P＜0.01）， while the content of CCK was increased significantly （P＜0.01）. No organic damage was found in all model groups. Compared with model group， L. aggregate stir-baking with vinegar group and A. lappa group， gastric emptying rate and small intestinal propulsion rate of rats were increased significantly in L. aggregate of stir-baking with vinegar-A. lappa group and mosapride group （P＜0.05 or P＜0.01）； serum contents of MTL and GAS were increased significantly （P＜0.01）， while the content of CCK was decreased significantly （P＜0.01）. CONCLUSIONS： L. aggregate of stir-baking with vinegar-A. lappa can accelerate gastric emptying and small intestinal propulsion rate of FDLDQS rats， increase serum contents of MTL and GAS but decrease the content of CCK； its effects are better than that of them alone.

Objective To retrieve and analyze the guidelines on diabetic foot offloading, and summarize the evidence of high quality guidelines, so as to provide reference for standardizing the offloading treatment of diabetic foot in China. MethodsThe clinical practice guidelines of diabetic foot in the major guideline networks, databases and professional association websites were retrieved by computer. Three researches evaluated the quality of the guidelines, and two researches extracted evidence from documents that met the quality criteria. ResultsA total of 7 guidelines were included, and 5 aspects, 30 recommendations were extracted, including comprehensive treatment, the principle of offloading, offloading of the plantar ulcer, offloading of the non-plantar ulcer, and the gap between the evidence and practice. ConclusionsThis study summarize the best evidence of the diabetic foot offloading therapy, and provides a reference for medical institution to develop appropriate procedures and standardize the practice of diabetic foot offloading therapy. Most of the interventions recommended in the guidelines come from relatively developed countries, but their application may be limited in less developed countries or regions. Therefore, it is urgent to explore offloading methods which have positive offloading effect as well as conform to our national conditions, and apply them to clinical practice gradually in order to improve the therapeutic effect of diabetic foot and improve prognosis.

Objective To explore the barriers in the clinical use of evidence-based urethral catheter cleaning. MethodsThe interview outline was developed based on the Theoretical Domains Framework (TDF) from September to October 2018. Totally 19 nurses working in the Department of Urinary Surgery at Peking University First Hospital was selected for semi-structural interview by convenient sampling, and content analysis was conducted based on the results. ResultsA total of 4 barriers related to 4 domains under the TDF were found in this study, namely, social / professional roles and identities, confidence in results, environmental factors and resources, and social impact. The subjects were extracted on this basis, which were lack of knowledge conversion process and norms in the department, poor self-management ability in the patients, and insufficient catheter cleaning resources. ConclusionsThe clinical use of evidence-based urethral catheter cleaning is affected by multiple factors, including systems, patients and resource availability. Departments need to explore and develop the norms for knowledge transformation, improve the self-management ability of postoperative patients, provide sufficient resources for catheter cleaning, and promote the clinical use of evidence-based urethral catheter cleaning.

Objective: To study the intracellular location and characteristic of SFTSV NP protein in different phases using mini singlet oxygen generator (miniSOG) labeling technique. Methods: MiniSOG is a recently-invented genetically-encoded tag for EM. MiniSOG-fused SFTSV NP (NPSOG) gene was cloned by PCR, and inserted into pcDNA3.0 plasmid to form pTPL-NPSOG, which was used to transfect 293 cells. The transfected cells of different phases were fixed in 2.5% glutaraldehyde in situ, stained with DAB through the photooxidation activity of miniSOG, and used to prepare ultrathin sections. Intracellular location and characteristic of SFTSV NP protein in different phases were studied by observing the sections under transmission electron microscope. Results: After transfecting the plasmid with NPSOG to 293 cells, NP protein was expressed in cytoplasm and peri nucleus, and gradually aggregated, which connected with endoplasmic reticulum and Golgi apparatus to form larger volume and irregular inclusion bodies in cytoplasm. No obvious subcellular structure changes were found. Conclusions The SFTSV nucleoprotein can be expressed separately to form inclusion bodies without the assistance of other viral proteins. The formation of inclusion bodies requires the directional movement and aggregation of a certain number of NP proteins, which may involve the interaction of NP protein and host organelles during this period.