Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ² test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.
Adolescent ; China/epidemiology* ; Electronic Nicotine Delivery Systems ; Humans ; Prevalence ; Students ; Tobacco ; Tobacco Smoke Pollution

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.
Ataxia/genetics* ; Child ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Retrospective Studies ; Spasms, Infantile/genetics*

Objective:To study the protective effect of different doses of single-flavored Coptis， Magnoliae Officinalis Cortex， and their compatibility on ulcerative colitis （UC） model rats and the colonic B lymphoblastoma-2 associated X protein （Bax） and cysteine-containing aspartame-3（Caspase-3） protein， inflammatory cytokines， and other expressions. Method:The 120 healthy adult SD rats were randomly divided into blank group， model group， sulfasalazine group， Coptidis Rhizoma 2.00， 1.00， 0.50 g·kg^-1 group， Magnoliae Officinalis Cortex 2.00， 1.00， 0.50 g·kg^-1 group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00， 2.00， 1.00 g·kg^-1 group， 12 groups with 10 rats in each group. The UC model was prepared by 2，4， 6-trinitrobenzene sulfonic acid/ethanol （TNBS/ethanol）. After 24 h of modeling， the rats were gavaged at 10 mL·kg^-1 for one time/d. After modeling， the mental state， activity state， hair luster， stool characteristics， and blood in the stool of each group were observed. After continuous administration for 6 days， colon tissues and spleen were taken after the last administration for 24 h. The ratio of colonic weight to length and spleen index was calculated. The degree of colonic injury was evaluated according to the colonic mucosal injury index （CMDI） score criteria. the histopathological observation was performed using hematoxylin-eosin staining （HE）. The expression levels of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and myeloperoxidase （MPO） in the serum of Coptidis Rhizoma 2.00 g·kg^-1 group， Magnoliae Officinalis Cortex 2.00 g·kg^-1 group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg^-1 were detected by enzyme-linked immunosorbent assay（ELISA） in blank group and model group. Western blot was used to detect the expression of Bax and Caspase-3 proteins in the colon of rats. Result:Compared with blank group， rats in model group were sluggish and less active. The colon weight-length ratio， spleen index， CMDI， and colon tissue pathological damage increased significantly， and the expression of serum TNF-α， IL-6， and MPO increased significantly. Serum IL-10 expression levels were extremely significantly reduced （P<0.01）. Compared with model group， the sulfasalazine group， the Coptidis Rhizoma 2.00， 1.00 g·kg^-1 group， the Magnoliae Officinalis Cortex 2.00 g·kg^-1 group， and the three-dose groups of Coptidis Rhizoma combine with Magnoliae Officinalis Cortex， their colon weight-length ratio and CMDI were significantly reduced （P<0.05，P<0.01）. The colon weight length ratio and CMDI index of the Coptidis Rhizoma 0.50 g·kg^-1 group， Magnoliae Officinalis Cortex 0.50 and 1.00 g·kg^-1 group were not significantly different from the model group but compared with Coptidis Rhizoma and Magnolia 0.50 g·kg^-1 group， the ratio of colon weight to length in the group of Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 1.00 g·kg^-1 group was significantly reduced （P<0.01）. Compared with model group， the spleen index of the sulfasalazine group， the Coptidis Rhizoma 2.00 g·kg^-1， and the Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg^-1 group were significantly lower （P<0.05）， compared with model group， the sulfasalazine group， Coptidis Rhizoma 2.00， 1.00 g·kg^-1 and Magnoliae Officinalis Cortex 2.00 g·kg^-1， thre dose groups of Coptidis Rhizoma combine with Magnoliae Officinalis Cortex can significantly improve the depth and scope of histopathological damage and tissue necrosis. Compared with the model group， the preferred Coptidis Rhizoma 2.00 g·kg^-1 group， Magnoliae Officinalis Cortex 2.00 g·kg^-1group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg^-1 group serum TNF-α， IL-6， MPO expression levels are extremely significantly reduced， the level of IL-10 increased significantly （P<0.01）．Compared with blank group， the expression of 　Bax and Caspase-3 protein in the colon of model group was significantly increased （P<0.01）. Compared with model group， the expression of Bax and Caspase-3 protein in preferred Coptidis Rhizoma 2.00 g·kg^-1 group and Magnoliae Officinalis Cortex 2.00 g·kg^-1 group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg^-1 group were significantly reduced （P<0.01）． Conclusion:The compatibility of single-flavored Coptidis Rhizoma， Magnoliae Officinalis Cortex， and Coptidis Rhizoma combine with Magnoliae Officinalis Cortex may improve the pathology of UC model rats induced by TNBS/ethanol by down-regulating the expression of Bax and Caspase-3 protein， inhibiting the release of inflammatory cytokines and promoting the release of anti-inflammatory factors injury， it plays a role in protecting colonic mucosa. The compatibility effect of Coptidis Rhizoma and Magnoliae Officinalis Cortex is better than that of single medicine， and Coptidis Rhizoma has a tendency to be better than Magnoliae Officinalis Cortex.