Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.

Entorhinal Cortex/physiology* ; Hippocampus/physiology* ; Neural Pathways/physiology*

To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8，2020，the information of 151 confirmed cases in Yueqing，Zhejiang province were obtained，including patients' infection process，population mobility between Yueqing and Wuhan，etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models，integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic，the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170，the actual monitoring number of cases in Yueqing as of April 27，2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.
COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Models, Theoretical ; Pandemics ; SARS-CoV-2

Objective:To explore the association between socioeconomic status (SES) and overweight/obesity in Yi people in Sichuan province.Methods:A cross-sectional study was conducted in Liangshan Yi Autonomous Prefecture in 2015. Stratified cluster sampling method was used to enroll Yi farmers and rural-to-urban Yi migrants aged 20-80 years. SES was measured by education level, personal annual income, and compound SES index. Unconditional logistic regression models were used to determine the association between SES and overweight/obesity (BMI≥24.0 kg/m 2). Results:1 894 Yi farmers and 1 162 rural-to urban migrants were included in the analysis. After adjustment for age, smoking, drinking and physical activity, compared with illiteracy, OR for farmer males with higher education level (primary or junior school, senior high school or higher) were 1.71 (95 %CI: 1.13-2.58) and 4.15 (95 %CI: 2.10-8.22). Compared with lower income group (<5 000 CNY/y), the higher income group had increased risk ( OR=1.66, 95 %CI: 1.12-2.44). For farmer males with medium and high SES level, the risk of overweight/obesity were 1.65 (95 %CI: 1.02-2.67) and 3.26 (95 %CI: 1.97-5.42) compared with low level of SES. For farmer females, the risk increased with the higher income, with OR as 1.49 (95 %CI: 1.10-2.02). Compared with low SES level, farmer females with medium level of SES was associated with 1.47 (95 %CI: 1.11-1.95) times higher risk of overweight/obesity. In Yi migrants, the association between SES and overweight/obesity was not found. Conclusion:Socioeconomic status was positively associated with overweight/obesity only in Yi farmers.

Cerebrospinal fluid surrounds and supports the central nervous system, including the ventricles and subarachnoid spaces. Cerebrospinal fluid should be an important source of biomarkers for central nervous system diseases because it is in direct contact with the central nervous system. Many studies are reported on cerebrospinal fluid proteomics, highlighting many recent progresses. Here, we review recent advances in proteomics technology and clinical application of cerebrospinal fluid.
Biomarkers ; Cerebrospinal Fluid Proteins ; Proteome ; Proteomics

Objective Analyzed surgical outcome following Flex-3D thoracoscopy among 429 cases with lobectomy and segmentectomy in this paper to define its safety and efficacy.Methods From the completion of the Olympus Flex-3D integrated operation room in Shanghai Chest Hospital in June 2015 up to December 2016,a single surgeons team carried out 429 cases of Flex-3D anatomic video-assisted thoracic surgery.Demography,preoperative condition,perioperative period complications and pathology for these patients were analyzed and discussed.Results There was a total of 429 patients including 258 males and 171 females.The age at diagnosis was ranged 21-81 yds.Lobectomy was performed in 313 cases,segmentectomy in 116 cases.Among those with 389 primary malignant tumors,39 benign tumors and 1 MALT were anatomically resected.The mean number of lymph nodes resected was 11.10 ±4.58(1-30) and mean sampled lymph node stations 6.10 ± 1.34(1-10).1patient was converted to thoracotomy because of vessel injury.The average operation time was 98.00 ±24.61 min(range,35-274 min) and the average blood loss was(97.9 ±24.6)ml(range,50-400 ml).The postoperative hospital stay was(5.6 ± 1.3) days on average.There was no operative death,and operative complications occurred in 18 patients(4.1％).The 1-year overall survival and 1-year disease-free survival for the lung cancer group were 100％ and 99.8％,respectively.Conclusion Flex-3D video-assisted thoracic surgery is a safe and effective surgical procedure featured by its added depth perception to facilitate operation and short learning curve.

Pharmacokinetics plays a key role in rational use of medicines.Many factors can affect the drug's pharmacokinetics.Previous studies mainly focused on the impact of hypoxia on hepatic drug metabolizing enzyme,but uncommon on drug transporters.Actually,drug transporter is a key factor for activation of the drugs transport across the cell membrane into the inside of cells,such as multidrug resistance protein (MDR),breast cancer resistance protein (BCRP),multidrug resistance associated protein (MRP),organic cation transporter (OCT),organic anion-transporting polypeptide (OATP),organic anion transporter (OAT),qligopeptide transporter (PEPT),etc.They are widely present in the small intestine villus epithelial cells,renal tubular epithelial cells,hepatocytes and biliary epithelial cells.They play a very important role in drug absorption,distribution,metabolism and excretion.The changes in drug transporters under hypoxia in intestinal could affect the bioavailability of drugs;the changes in drug transporters in organs could affect drug's distribution,subsequent drug's indications and adverse reactions;the changes in drug transporters in liver and kidney could affect the metabolism and excretion rate of drugs,thereby the drug's residence time and half-life.

Objective To investigate the effects on myocardial mitochondria-related indexes in rats after rapid elevation to 3 400 m altitude and myocardial protection effects with metoprolol.Methods Male Wistar rats were randomly divided into three groups with 12 rats in each group as follows,group A(normal group,55 m above sea level),group B(hypoxia group, 3 400 m above sea level),group C(metoprolol group,3 400 m above sea level).Heart rate and blood pressure were measured during the rapid transfer from the plain(Shanghai 55 m)to plateau of 3 400 m.Then,the rats were anesthetized with chloral hydrate.The blood was collected from the abdominal aorta and blood gas indexes were measured.The heart tissue was homog-enized.The oxidativee stress related parameters,such as superoxide dismutase(SOD),malondialdehyde(MDA)and nitric ox-ide(NO)were assayed.The mitochondrial function related parameters,such as complexes-Ⅰ,Ⅱ,Ⅲ,Ⅳ,succinate dehydro-genase(SDH),malate dehydrogenase(MDH)and adenosine triphosphate(ATP)were measured.Results After the rats were exposed to high altitude,the blood oxygen tension and oxygen saturation in the metoprolol group were increased in com-parison with the hypoxia group.Compared with the normal group,the content of MDA in the hypoxia group was increased sig-nificantly,while the content of SOD and NO were decreased significantly(P<0.01),the mitochondrial complex Ⅰ,Ⅱ,Ⅲand Ⅳ were also decreased 44.49%,32.38%,34.43% and 20.16%.Compared with hypoxia group,the MDA was decreased by 13.72%,while SOD and NO were increased by 25.73% and 168.55%,the activity of mitochondrial complexes were also increased by 44.92%,33.73%,37.11% and 10.09% for metoprolol group.The respiratory chain SDH and MDH in hypoxic group were decreased by 29.51% and 42.79% and the activity of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and T-ATPase were decreased by 20.24%,27.56% and 33.32% in comparison with the normal group.After intervention with metoprolol,SDH and MDH were increased by 47.36% and 88.57% separately,the activities of Na+-K+-ATPase,Ca2+-Mg2+-ATPase and T-ATPase were also increased by 31.92%,26.95%,44.93% in comparison with hypoxia group.Those results indicated that metoprolol can increase ATPase activity.Conclusion Under the condition of acute hypoxia at 3 400 m above sea level,myocar-dial injury is related to the changes of oxidative stress and mitochondrial-related enzyme activity.Metoprolol helps to normalize the related indicators and provides the protection for myocardial injury caused by hypoxia.

Objective To investigate the anti-hypoxia effects of octacosane and the petroleum ether extract from Saus-surea Involucrate(PESI)on the water,sugar,lipid and protein metabolism of mice at simulated high altitude.Methods The healthy adult male BALB/C mice were randomly divided into normal control group,hypoxic model group,acetazolamide group, the petroleum ether of Saussurea involucrata group and octacosane group.Drugs were administered i.v 20 mins before the mice were exposed to a simulated high altitude of 6 000 m for 8 hours in an animal decompression chamber.The mice were sacrificed at the end of 8 hours.Organ water content,organ indexes and metabolism indicators of sugar,protein and lipid were deter-mined.Results The edema of heart,brain and lung was reduced notably(P<0.05,P<0.01)in the mice received PESI at 200 mg/kg and octacosane at 100 mg/kg.In the treated groups,the increase of blood sugar,muscle glycogen,TG(triglycer-ide),TC(total cholesterol)were all significantly inhibited,the decrease of liver glycogen,the protein content of heart and brain was also remarkably blocked(P<0.05,P<0.01).Conclusion PESI and octacosane effectively regulate the metabolism of hypoxic mice and reserve the body′s energy for survival by lowering the basic metabolism.

Objective To study pharmacodynamics of the effective anti-hypoxia components in the petroleum ether ex-tract of Saussurea Involucrate(PESI)and octacosane.Methods PESI and octacosane were first evaluated by normobaric hy-poxia model,acute decompression model and followed by chemical induced hypoxic models with potassium cyanide,sodium ni-trite and isoprenaline hydrochloride poisoning.Results PESI and octacosane can effectively prolong the survival time of hypo-baric hypoxic mice(P<0.01)and reduce the mortality of acute hypobaric hypoxia mice(P<0.01)in a dose-dependent man-ner.Anti-hypoxic potency of PESI and octacosane obtained by chemical induced hypoxic model indicated that they significantly increase survival time(P<0.05)of hypoxia mice than acetazolamide.Conclusion PESI and octacosane have good anti-hypoxia activity.