Hsa_circ_0013561 promotes progression of nasopharyngeal carcinoma by activating JAK2/STAT3 signaling pathway.

OBJECTIVE: Nasopharyngeal Carcinoma (NPC) is a malignancy of epithelium of epithelium of the nasopharynx, with the highest incidence of otolaryngeal malignancies. A growing number of studies confirm that Circular RNA (circRNA) plays an important role in tumor development, including Hsa_circ_0013561. This study aims to elucidate the process and mechanism of NPC regulation hsa_circ_0013561. METHODS: In this study, circRNA expression nodes and subcellular localization in NPC tissues were analyzed by fluorescence in situ hybridization. The expression of hsa_circ_0013561 in NPC cells was further clarified by RT-qPCR. At the same time, the lentivirus vector interfered by hsa_circ_0013561 was constructed and transfected. The cell proliferation was detected by CCK-8 method, EdU assay and plate cloning assay. The cell cycle and apoptosis were detected by flow cytometry, and the cell migration ability was detected by wound healing assay and Transwell assay. Western blotting examined the expression of apoptosis, Epithelial-Mesenchymal Transition (EMT)-associated proteins, and Janus Kinase/Signal Transductor and Activator of Transcription (JAK/STAT) signaling pathway-related proteins. RESULTS: The results showed that the expression of hsa_circ_0013561 in NPC samples was significantly upregulated and hsa_circ_0013561 localized in the cytoplasm. After down-regulating hsa_circ_0013561 expression, it significantly inhibited the proliferation and metastasis ability of NPC, inhibited EMT progression, and promoted apoptosis. Further studies showed that interference hsa_circ_0013561 significantly inhibited JAK2/STAT3 signaling pathway activation and induced the expression of apoptosis-related proteins. CONCLUSION: In summary, we found that hsa_circ_0013561 is a pro-tumor circRNA in NPC, which can reduce the activation of JAK2/STAT3 pathway by knocking down hsa_circ_0013561, thereby slowing down the malignant progression of NPC. OXFORD CENTRE FOR EVIDENCE-BASED MEDICINE 2011 LEVELS OF EVIDENCE: Level 4.

Hsa_circ_0013561 promotes progression of nasopharyngeal carcinoma by activating JAK2/STAT3 signaling pathway

Abstract Objective Nasopharyngeal Carcinoma (NPC) is a malignancy of epithelium of epithelium of the nasopharynx, with the highest incidence of otolaryngeal malignancies. A growing number of studies confirm that Circular RNA (circRNA) plays an important role in tumor development, including Hsa_circ_0013561. This study aims to elucidate the process and mechanism of NPC regulation hsa_circ_0013561. Methods In this study, circRNA expression nodes and subcellular localization in NPC tissues were analyzed by fluorescence in situ hybridization. The expression of hsa_circ_0013561 in NPC cells was further clarified by RT-qPCR. At the same time, the lentivirus vector interfered by hsa_circ_0013561 was constructed and transfected. The cell proliferation was detected by CCK-8 method, EdU assay and plate cloning assay. The cell cycle and apoptosis were detected by flow cytometry, and the cell migration ability was detected by wound healing assay and Transwell assay. Western blotting examined the expression of apoptosis, Epithelial-Mesenchymal Transition (EMT)-associated proteins, and Janus Kinase/Signal Transductor and Activator of Transcription (JAK/STAT) signaling pathway-related proteins. Results The results showed that the expression of hsa_circ_0013561 in NPC samples was significantly upregulated and hsa_circ_0013561 localized in the cytoplasm. After down-regulating hsa_circ_0013561 expression, it significantly inhibited the proliferation and metastasis ability of NPC, inhibited EMT progression, and promoted apoptosis. Further studies showed that interference hsa_circ_0013561 significantly inhibited JAK2/STAT3 signaling pathway activation and induced the expression of apoptosis-related proteins. Conclusion In summary, we found that hsa_circ_0013561 is a pro-tumor circRNA in NPC, which can reduce the activation of JAK2/STAT3 pathway by knocking down hsa_circ_0013561, thereby slowing down the malignant progression of NPC. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 4.

Research progress on the role of cardiac myosin binding protein-C in cardiovascular diseases / 新乡医学院学报

Cardiac myosin binding protein-C(cMyBP-C),as an important component of myocardium coarse filaments,can regulate cross-bridge circulation through phosphorylation or dephosphorylation and participates in myocardial systolic and diastolic functions.cMyBP-C plays an important role in the occurrence and development of cardiovascular diseases(CVDs)such as acute myocardial infarction,cardiomyopathy,heart failure,aortic stenosis,hypertensive myocardial hypertrophy,and myocarditis,but the specific mechanism has not been fully clarified.This article reviews the research progress on the role of cMyBP-C in CVDs,in order to provide references for the diagnosis,treatment and prognosis evaluation of CVDs.

Clinical application of metagenomic next-generation sequencing in acquired immunodeficiency syndrome patients with pulmonary infections / 中华传染病杂志

Objective:To investigate the pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients with pulmonary opportunistic infections in the local area, and to evaluate the clinical application of metagenomic next-generation sequencing (mNGS) in these patients.Methods:From January to December 2021, AIDS patients with pulmonary infections admitted to Zhongnan Hospital of Wuhan University were enrolled. Their bronchoalveolar lavage fluid (BALF) was subjected to mNGS and coventional pathogen detection.Routine pathogen detection methods included smear, culture, polymerase chain reaction (PCR), and immunochromatographic colloidal gold. Fisher′s exact probability method was used for statistical analysis.Results:A total of 69 patients were included, and all of them were tested positive for mNGS. Among them, 53 cases (76.8%) were positive for fungi and viruses, 40 cases (58.0%) were positive for bacteria (excluding Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM)), six cases were positive for MTB, 11 cases were positive for NTM, and seven cases were positive for other pathogens. Mixed infections with two or more pathogens were found in 89.9%(62/69) of the patients. Among the conventional pathogen detections of BALF, 79.7%(55/69) of the patients were positive for pathogens, including 42 cases positive for Pneumocystis jirovecii PCR, 16 cases positive for BALF culture, nine cases positive for MTB PCR, and five cases positive for Cryptococcus antigen. The total detection rate of mNGS was 100.0%(69/69), which was higher than that of the conventional pathogen detection rate of 79.7%(55/69), and the difference was statistically significant (Fisher′s exact probability method, P<0.001). The specificity of mNGS detection was 88.4%. Combining clinical and two detection methods, the top five pathogens were Pneumocystis jirovecii (62.3%(43/69)), Candida (29.0%(20/69)), MTB (20.3%(14/69)), NTM and Talaromyces marneffei (15.9%(11/69), each). Fifty-three patients (76.8%) had co-infection with virus. Conclusions:The main cause of pulmonary infection in AIDS patients in this area is mixed infection, and Pneumocystis jirovecii is the most common pathogen. mNGS could significantly improve the pathogen detection rate in AIDS patients with pulmonary infections.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Clinical characteristics and survival comparison between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with cervical cancer / 肿瘤研究与临床

Objective:To summarize the clinical features and survival differences between human immunodeficiency virus (HIV)-positive and HIV-negative cervical cancer patients, and to explore the factors influencing the prognosis.Methods:The clinical data of patients with cervical cancer diagnosed and treated in Zhongnan Hospital of Wuhan University from January 2015 to January 2022 were retrospectively analyzed. There were 46 HIV-positive cases and 587 HIV-negative cases; all 46 HIV-positive patients had squamous cell carcinoma, while 504 HIV-negative patients had squamous cell carcinoma. According to age and clinical staging, 230 HIV-negative squamous cell carcinoma patients were screened to match with 46 HIV-positive squamous cell carcinoma patients according to 1∶5. The clinical features of HIV-positive and HIV-negative patients were compared in all matched patients with pathological type of squamous cell carcinoma; the Kaplan-Meire method was used to analyze the overall survival (OS) and the comparison of OS was made by using log-rank test. Multivariate Cox proportional risk model was used to analyze the independent factors affecting the OS of patients with cervical squamous cell carcinoma.Results:The differences in the age, pathological types, clinical staging between 46 HIV-positive patients and 587 HIV-negative patients were statistically significant (all P < 0.05). There were statistically significant differences in age and clinical staging between 46 HIV-positive squamous cell carcinoma patients and 504 HIV-negative squamous cell carcinoma patients (all P < 0.05). After 1∶5 matching, there were no statistically significant differences in the age, clinical staging between 46 patients with HIV-positive squamous cell carcinoma and 230 patients with HIV-negative squamous cell carcinoma. The OS of HIV-positive patients in the entire group,pathological type of squamous cell carcinoma or after pairing was worse than that of HIV-negative patients (all P < 0.001). The median OS time of HIV-positive patients was 63 months (95% CI 61-109 months), while the median OS time of HIV-negative patients was not reached (95% CI 165-178 months, 164-178 months, 143-173 months, respectively). Multivariate Cox regression analysis showed that clinical staging Ⅲ-Ⅳ was an independent risk factor for OS in patients with cervical squamous cell carcinoma (Ⅲ-Ⅳ vs. Ⅰ-Ⅱ: HR = 1.573, 95% CI 1.032-2.397, P = 0.035); HIV infection was an independent protective factor for OS (HIV-positive vs. HIV-negative: HR = 0.087, 95% CI 0.042-0.182, P < 0.001), indicating that HIV-positive patients had an advantage in OS compared to HIV-negative patients at the same age and clinical staging. Age was not an independent influencing factor for OS ( P > 0.05). Conclusions:The onset age of HIV-positive cervical cancer tends to be younger and the clinical staging is late when patients are diagnosed. HIV-positive patients have poor prognosis.

Effects of lung protective ventilation on brain function in patients with traumatic brain injury / 中华急诊医学杂志

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) ventilation strategy guided by driving pressure on intraoperative intracranial pressure in patients with moderate traumatic brain injury (TBI).Methods:Total of 111 patients aged 18-65 years old, with BMI of 17-28 kg/m 2, ASA grade of Ⅲ-Ⅳ, and Glasgow coma score of 9-11 before operation were treated with evacuation of intracranial hematoma in emergency. The patients were randomly divided into 0 cmH 2O PEEP group (Group 0 PEEP), 5 cmH 2O PEEP group (Group 5 PEEP) and individualized PEEP ventilation group (Group P) guided by driving pressure. The volume control ventilation mode is adopted, VT is 6 mL/kg, FiO 2 is 60%, and the inspiratory expiratory ratio is 1:2. Patients in Group 0 PEEP and Group 5 PEEP were given PEEP 0 or 5 cmH 2O for ventilation after tracheal intubation until the end of the operation. Patients in Group P were given individualized PEEP titration ventilation strategy guided by driving pressure after intubation. Blood gas analysis was performed at 5 min (T1) after tracheal intubation, 60 min (T3) after operation, and 5 min (T4) after operation. PaO 2, PaCO 2, and dynamic compliance (Cdyn) were recorded. The optic nerve sheath diameter (ONSD) was measured before anesthesia induction (T0), after PEEP titration in group P (T2, 10 min after ventilation in group 0 PEEP and 5 PEEP) and at T4; Serum neuron specific enolase (NSE) concentration was measured by ELISA before and 1 day and 3 days after operation; The occurrence of nervous system complications (intracranial infection, intracranial hypertension, epilepsy, brain edema, etc.) within 30 days after operation was followed up. Results:Compared with group 0 PEEP and 5 PEEP, Cdyn and PaO 2 in group P increased at T3-4 ( P<0.05), ONSD was not significantly different among the three groups ( P>0.05), NSE in group P decreased significantly at 1 and 3 days after operation, and the incidence of neurological complications in the three groups was not significantly different at 30 days after operation ( P>0.05). Conclusions:Individualized PEEP ventilation strategy guided by driving pressure can help improve lung and brain function in TBI patients.

Analysis on the factors influencing the return of deferred apheresis platelet donors due to abnormal health examination before donation / 现代医院

Objective Analyze the characteristics of delayed apheresis platelet donors due to health consultation or ex-amination,and the influencing factors of recall in Guangzhou,and to provide evidence for recruitment strategy.Methods 5 960 delayed apheresis platelet donors from January fisrt,2022 to June 30th,2022 were collected in Guangzhou Blood Center and fol-lowed up to August31th,2023.Logistic regression analysis was used to analyze the influence of sex,age,times of blood donation and length of blood donation on recall.Results Among the 5 960 delayed platelet donors,164(2.75%)were permanently un-suitable for blood donation.The most common reason was allergy.Among the 5 796(97.25%)delayed blood donors,the most common reason was abnormal blood routine.Analysis of factors associated with delayed donor recall found that male donors were more likely than female donors[OR =1.16,95%CI(1.01,1.34)],blood donors aged 26-35[OR =1.65,95%CI(1.41,1.92)],36-45[OR=1.90,95%CI(1.55,2.31)]or 46-60[OR =2.63,95%CI(1.96,3.53)]compared with those aged 18-25,blood donors who were blocked forless than 14 days[OR =4.22,95%CI(2.73,6.52)]orfor 15-89 days[OR =5.24,95%CI(3.42,8.03)]compared with those who were blocked for more than or equal to 90 days,the recall rate of repeat donors was higher than that of first-time donors[OR=6.78,95%CI(5.62,8.19)].Conclusion In order to improve the recall rate of apheresis platelet donors,we should pay more attention to the education of young donors and first-time donors,also consider a voluntary recall by text message or phone after a donor has been prevented from donating blood.

A case of ganglioneuroma of the ureter and review of the literature.

Ganglioneuroma is a rare tumor originating from neural crest tissue of the sympathetic nervous system. We report on an approximately 55-year-old woman who was admitted to hospital with abdominal pain. Surgery revealed a tumor in her right ureter, which was pathologically confirmed as a ganglioneuroma. The patient underwent transabdominal total hysterectomy, bilateral adnexal resection, release of pelvic and intestinal adhesions, right ureteroscopy, right ureter retrograde intubation, right ureteral lesion excision, and ureteral anastomosis. A literature review indicated that most ganglioneuromas are benign tumors. Clinicians may consider total or subtotal tumor resection, depending on the tumor location and patient's condition. The patient's clinical condition may improve after surgery combined with periodic long-term follow-up.

The effects of vaccination on the disease severity and factors for viral clearance and hospitalization in Omicron-infected patients: A retrospective observational cohort study from recent regional outbreaks in China

ObjectIt remains unelucidated regarding the effects of vaccination on disease severity and factors for viral clearance and hospitalization in omicron-infected patients. MethodsThe clinical manifestations of 3,265 Omicron-infected patients (BA.2 variant; the Omicron group) were compared with those of 226 Delta-infected patients (the Delta group).A Multi-class logistic regression model was employed to analyze the impacts of vaccination doses and intervals on disease severity; a logistic regression model to evaluate the risk factors for hospitalization; R 4.1.2 data analysis to investigate the factors for time for nucleic acid negativization (NAN). ResultsCompared with the Delta group, the Omicron group reported a fast transmission, mild symptoms, and lower severity incidence, and a significant inverse correlation of vaccination dose with clinical severity (OR: 0.803, 95%CI: 0.742-0.868, p<0.001). Of the 7 or 5 categories of vaccination status, the risk of severity significantly decreased only at [≥]21 days after three doses (OR: 0.618, 95% CI: 0.475-0.803, p<0.001; OR: 0.627, 95% CI: 0.482-0.815, p<0.001, respectively). The Omicron group also reported underlying illness as an independent factor for hospitalization, sore throat as a protective factor, and much shorter time for NAN [15 (12,19) vs. 16 (12,22), p<0.05]. NAN was associated positively with age, female gender, fever, cough, and disease severity, but negatively with vaccination doses. ConclusionBooster vaccination should be advocated for COVID-19 pandemic-related control and prevention policies and adequate precautions should be taken for patients with underlying conditions.

Standardized establishment and informationized management of liver cancer biobank / 临床肝胆病杂志

Objective To establish a small liver cancer biobank with a standard operating procedure and the function of informationized management. Methods According to the inclusion and exclusion criteria, blood, tissue, and stool samples were collected from the patients with liver cancer who attended Liver Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, from August 2012 to December 2020 and signed the informed consent. In-and-out-of-storage management was performed based on the standard procedure for whole blood, serum, frozen tissue, paraffin-embedded tissue, and stool samples, and related clinical and follow-up data were collected. The frozen samples of liver cancer tissue and adjacent tissue in different years were randomly selected, and the concentration and completeness of total RNA were examined to ensure the quality of frozen samples stored in the biobank. Results The samples were collected from 4190 liver cancer patients who underwent surgery within a period of 101 natural months, and there were 41718 frozen tissue samples, 18950 paraffin-embedded tissue samples, 24389 whole blood samples, 20060 serum samples, and 5392 stool samples. The liver cancer patients had an age range of 13-88 years, and male patients accounted for 85.1%. The patients with hepatitis B accounted for 83.3%, and those with liver cirrhosis accounted for 73.5%. A standard operating procedure and an electronic data capture system were developed according to the collection, processing, storage, application, and informationized management of samples. Among the 18 frozen tissue samples randomly selected from the biobank, 16 samples had high RNA quality, which could meet the requirements of subsequent experiments. Conclusion A standardized and informationized biobank has been established for liver cancer, which provides high-quality samples for the basic research on liver cancer and helps to explore the research value of samples.

Feasibility of programmed death-1 monoclonal antibody treatment for patients with acquired immunodeficiency syndrome complicated with malignant tumor / 中华传染病杂志

Objective:To investigate the feasibility, efficacy and adverse reactions of programmed death-1(PD-1) inhibitors in patients with acquired immunodeficiency syndrome (AIDS) complicated with malignant tumor.Methods:From September 2020 to August 2021, patients with AIDS complicated with malignant tumor in Zhongnan Hospital of Wuhan University were enrolled. Data including basic information, laboratory test results, CD4 + T cell count, human immunodeficiency virus (HIV) viral load were collected. Patients were continuously administered intravenously PD-1 monoclonal antibody until disease progression or intolerant toxicity reaction occurred. Adverse reactions during treatment were recorded.And treatment outcomes were assessed once every 12 weeks after treatment. HIV viral load was measured after treatment once a week for four consecutive times, then once four weeks for two consecutive times, and then once every 12 weeks. Results:Ten patients were included in the study, including seven males and three females, three cases of Hodgkin′s lymphoma, two cases of cervical cancer and hepatocellular carcinoma respectively, one case of non-Hodgkin′s lymphoma, non-small cell lung cancer and anal cancer respectively. There were four patients with CD4 + T cell count of 100 to 200 cells/μL and two patients with CD4 + T cell count lower than 100 cells/μL. All patients had completed at least three cycles of treatment with PD-1 monoclonal antibody, HIV viral load remained lower than 20 copies /mL. Three cases achieved complete response and three cases achieved partial response. Adverse reactions were cutaneous capillary endothelial proliferation (CCEP) (seven cases), major bleeding (three cases), and hearing impairment (one case). Conclusions:PD-1 inhibitor has no adverse effect on the continuous suppression of HIV viral load and has an effect on tumor control, so it is a viable choice in AIDS patients complicated with tumor. However, due to its considerable adverse reactions, multidisciplinary cooperation is needed to reduce the risk of complications and deal with serious complications.

Safety and efficacy of high-flow nasal oxygen for pre-oxygenation before anesthesia induction: a meta-analysis / 中华麻醉学杂志

Objective:To systematically review and evaluate the safety and efficacy of high-flow nasal oxygen (HFNO) for pre-oxygenation before anesthesia induction.Methods:Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database and China Biomedical Literature Database were searched from inception to March 2022.All randomized controlled trials comparing HFNO and facemask ventilation for pre-oxygenation before anesthesia induction were collected.Two researchers independently assessed the quality of trials and extracted data.The primary outcome was the safe apnea time, the secondary outcomes were the lowest SpO 2 during intubation, oxygenation-related complications, patient comfort, PaO 2 and PaCO 2 before and after pre-oxygenation and after intubation.Meta-analysis was performed using RevMan 5.4 software. Results:Seventeen randomized controlled trials involving 843 patients were included in this meta-analysis.The results of meta-analysis showed that the safe apnea time was significantly longer ( MD=67.61, 95% CI 5.94-129.28, P=0.03), the lowest SpO 2 was higher during tracheal intubation ( MD=3.27, 95% CI 2.25-4.29, P<0.01), and PaO 2 was higher after pre-oxygenation ( MD=54.39, 95% CI 9.32-99.46, P=0.02) in the patients using HFNO than those using facemask ventilation.There were no statistically significant differences in the other outcomes ( P>0.05). Conclusions:HFNO for pre-oxygenation before anesthesia induction can significantly prolong the safe apnea time, increase the lowest SpO 2 during tracheal intubation, and improve the levels of PaO 2 after pre-oxygenation, and HFNO does not affect the patient′s comfort or increase the development of preoxygenation-related complications when compared with facemask ventilation.

A need of COVID19 vaccination for children aged <12 years: Comparative evidence from the clinical characteristics in patients during a recent Delta surge (B.1.617.2)

ObjectiveTo evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics in unvaccinated children aged < 12 y with vaccinated patients aged [≥] 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. MethodsA total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Realtime PCR positive and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged [≥] 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; the effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. ResultsThe Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged [≥] 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84(1.32,2.71)x10^9/L vs. 1.31(0.94,1.85)x10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28(3.31,8.13) vs. 9.10(4.37,15.14); p< 0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13(0.00,0.09) vs. 0.12(0.03,0.41), p<0.05; 0.02(0.00,0.14) vs. 1.94(0.54,6.40), p <0.05; 5.46(2.41,9.26) vs. 73.63 (54.63,86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). ConclusionChildren aged < 12y may be critical hidden spreaders, which indicates an urgent need of vaccination for this particular population.

CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease is autocrine TNF-α/TNFRI-dependent

Lymphopenia is common in severe COVID-19 disease, yet the mechanisms are poorly understood. In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared to recovered, mild disease (p<0.0001). In severe disease, immunodominant CD4+ T cell responses to Spike-1(S1) produced increased in vitro TNF-, but impaired proliferation and increased susceptibility to activation-induced cell death (AICD). CD4+TNF-+ T cell responses inversely correlated with absolute CD4+ counts from severe COVID-19 patients (n=76; R=-0.744, P<0.0001). TNF- blockade including infliximab or anti-TNFRI antibodies strikingly rescued S1-specific CD4+ proliferation and abrogated S1-AICD in severe COVID-19 patients (P<0.001). Single-cell RNAseq demonstrated downregulation of Type-1 cytokines and NF{kappa}B signaling in S1-stimulated CD4+ cells with infliximab treatment. Lung CD4+ T cells in severe COVID-19 were reduced and produced higher TNF- versus PBMC. Together, our findings show COVID-19-associated CD4+ lymphopenia and dysfunction is autocrine TNF-/TNFRI-dependent and therapies targeting TNF- may be beneficial in severe COVID-19. One Sentence SummaryAutocrine TNF-/TNFRI regulates CD4+ T cell lymphopenia and dysfunction in severe COVID-19 disease.

Effects of different fractions of inspired O 2 during general anesthesia induction on perioperative pulmonary function in patients undergoing gynecological laparoscopic surgery / 中华麻醉学杂志

Objective:To compare the effects of different fractions of inspired O 2 (FiO 2) during general anesthesia induction on perioperative pulmonary function in patients undergoing gynecological laparoscopic surgery. Methods:A total of 100 patients, aged 30-64 yr, with body mass index<30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective total laparoscopic hysterectomy, were divided into 4 groups ( n=25 each) using a random number table method: group A, group B, group C and group D. In A, B, C and D groups, FiO 2 was 40%, 60%, 80% and 100%, respectively.Immediately after the establishment of electrocardiogram monitoring after entering the operation room (T 0), immediately after tracheal intubation (T 1), immediately after creation of pneumoperitoneum (T 2), at 30 min of pneumoperitoneum (T 3), immediately before tracheal intubation (T 4) and at 15 min after tracheal intubation (T 5), ventral (ROIⅠ), middle ventral (ROIⅡ), middle dorsal (ROIⅢ) and dorsal (ROI Ⅳ) lung ventilation were recorded using electrical impedance tomography.The impedance ratio (IR) was calculated and the safety time without ventilation was recorded.Blood samples were collected from the radial artery at T 0-2 and T 5 for blood gas analysis, arterial oxygen partial pressure (PaO 2) and arterial carbon dioxide partial pressure (PaCO 2) were recorded, and oxygenation index (OI) was calculated.The occurrence of pulmonary complications within 3 days after operation was recorded. Results:Compared with group D, the ventilation in ROIⅠ and ROIⅡwas significantly increased, the ventilation in ROIⅢ and ROIⅣ was decreased, and IR was increased at T 1 and T 2 in A, B and C groups, PaO 2 and OI were decreased at T 1, and the safety time without ventilation was prolonged in A and B groups, and PaO 2 was decreased, OI was increased at T 1 ( P<0.05), and no significant was change in the safety time without ventilation in group C ( P>0.05). There was no significant difference in the incidence of pneumoperitoneum among the 4 groups ( P>0.05). Conclusion:During general anesthesia induction, 80% FiO 2 has the least effect on lung function in the patients undergoing gynecological laparoscopic surgery.

Application of bilingual mixed grouping in ward round teaching for overseas students in cardiology department / 中华医学教育探索杂志

Due to the problems of language barriers and cultural differences existing in the current clinical practice teaching activities of overseas students, this study proposes to divide the oversea students and Chinese students into bilingual mixed groups in the ward rounds teaching. Through the selection of typical cases and the application of flipped classroom, the Chinese and English versions of learning materials related to disease are provided to the interns for learning in advance, and the oversea students and Chinese students are requested to complete the history and auxiliary examination data collection in Chinese and English in cooperation, and then the teacher leads the group to carry out ward rounds teaching, including bedside English history report, physical examination, case analysis, discussion and summary, so as to improve the participation enthusiasm of overseas students and also improve the teaching effects.

Development of a novel high throughput brain-on-chip with 3D structure and its application in evaluation of pesticide-induced-neurotoxicity / 生物工程学报

We designed and fabricated a novel high throughput brain-on-chip with three dimensional structure with the aim to simulate the in vivo three-dimensional growth environment for brain tissues. The chip consists of a porous filter and 3D brain cell particles, and is loaded into a conventional 96-well plate for use. The filter and the particle molds were fabricated by using computer modeling, 3D printing of positive mold and agarose-PDMS double reversal mold. The 3D cell particles were made by pouring and solidifying a suspension of mouse embryonic brain cells with sodium alginate into a cell particle mold, and then cutting the resulting hydrogel into pieces. The loaded brain-on-chip was used to determine the neurotoxicity of pesticides. The cell particles were exposed to 0, 10, 30, 50, 100 and 200 µmol/L of chlorpyrifos or imidacloprid, separated conveniently from the medium by removing the porous filter after cultivation. Subsequently, cell proliferation, acetylcholinesterase activity and lactate dehydrogenase release were determined for toxicity evaluation. The embryonic brain cells were able to grow and proliferate normally in the hydrogel particles loaded into the filter in a 96-well plate. Pesticide neurotoxicity test showed that both chlorpyrifos and imidacloprid presented dose-dependent inhibition on cell growth and proliferation. Moreover, the pesticides showed inhibition on acetylcholinesterase activity and increase release of lactate dehydrogenase. However, the effect of imidacloprid was significantly weaker than that of chlorpyrifos. In conclusion, a novel brain-on-chip was developed in this study, which can be used to efficiently assess the drug neurotoxicity, pharmacodynamics, and disease mechanism by combining with a microtiterplate reader.

Application of robotic surgical system in hepatic surgery / 中华消化外科杂志

The robotic surgical system can provide a stable, clear and magnified three-dimensional view, filter the surgeon's hand tremor, and hold robotic arms with multiple degrees of freedom to ensure flexible and stable operations, which overcomes the shortcomings of traditional laparoscopy. Although the robotic surgical system has been widely used in surgical fields such as urology, obstetrics and gynecology, its role in hepatic surgery has not been fully recognized. In this article, based on the relevant literatures and their own experience, the authors briefly discuss the indications of the application of robotic surgical system in liver surgery, safety and efficacy of robotic liver resection, learning curve of robotic hepatectomy, difficult robotic hepatectomy, the cost of robotic liver resection and other issues.

Clinical Characteristics Hospitalized Patients with SARS-Cov-2 and HBV Co-infection

Background & AimsThe coronavirus disease 2019 (COIVD-19) caused by SARS-CoV-2 has been characterized as a pandemic, which causes a serious public health challenge in the world. A very large group of patients infected by HBV has been reported worldwide, especially in China. In order to answer whether specific treatment strategy on the patients coinfected with HBV and SARS-CoV-2, it requires profound understanding of the clinical characteristics on those patients. However, the impacts of SARS-CoV-2 infection on HBV patients remain largely unknown. Approach & ResultsIn this retrospective investigation, we included 123 COVID-19 patients admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from January 5 to March 7, 2020. All enrolled patients are the laboratory confirmed COVID-19 pneumonia cases according to the criteria reported previously. A total of 123 patients were analyzed for their Clinical records, laboratory results including the diagnosis of HBV infection and liver function. Among 123 confirmed COVID-19 patients, the mean age was 51 years old and 59.3% were females (73/123). Fifteen were previously HBV infected patients, 66.7% of them were males (10/15), patients with HBV infection appeared to have a higher incidence of liver cirrhosis and an increased level of total bilirubin. Seven (46.7%) patients with HBV infection were defined as severe cases, while the severity rate was 24.1% for the patients without HBV infection (26/108). The mortality of patients with HBV infection was 13.3% (2/15) compared to 2.8% (3/108) for the patients without HBV infection. ConclusionsSARS-CoV-2 infection may cause Live function damage in COVID-19 cases and the patients with HBV infection are likely to have more severe disease outcome.