Toxin-antitoxin system (TA) is a genetic element widely found in chromosomes and plasmids of bacteria, archaea and prophages. TA usually consists a toxin that inhibits the growth of bacteria and an antitoxin that neutralizes its toxicity. Since the discovery of the first CcdB / CcdA TA in the 1980s, TA has been proved to exist in almost all sequenced microorganisms and plays an important role in maintaining plasmid stability, anti-phage and promoting biofilm formation. At present, TA is divided into type I-VIII, among which type IITA is the most widely studied. HipBA is a type II TA. The toxin HipA in Escherichia coli HipBA is a serine / threonine kinase, which inhibits protein translation by phosphorylating bacterial Glutamyl tRNA synthetase (GltX), and its toxicity can be specifically neutralized by HipB. Recently, it has been found that Escherichia coli HipA homologous proteins exist widely in microorganisms, and they form a potential novel TA with genes of the same promoter, in which HipBST has been confirmed by experiments. The toxin HipT and the antitoxin HipS in this TA are similar to the C-terminal and N-terminal of E. coli HipA respectively, and the neutralization mechanism and the substrate of the toxin are different from that of E. coli toxin HipA. This study summarizes the recent discovery of special TA, especially the neutralization mechanism of HipBST which widely exists in prokaryotes.

Bunyavirus is widely distributed, highly contagious, and has a high fatality rate. It is a negative- strand RNA virus that has a major impact on public health around the world. The development of vaccines and the search for drugs are the key to prevent bunyavirus infection. The nucleoprotein (NP) of viruses is necessary for the synthesis of viral RNA, which combines with viral RNA to form the nucleocapsid, participates in viral assembly and RNA transcription, and plays an important role in viral proliferation. In addition, NP also has B cell and T cell epitopes, which can induce cellular and humoral immunity, so NP is an ideal target for vaccine design and drug development. Given its abundance and specificity, NP is also commonly used in the detection of viral diseases. More and more bunyavirus NP structures and structures of NP-RNA complexes have been resolved. Researchers have discovered two important antiviral targets through these structures, the terminal arm and the RNA binding cleft. This paper reviews the function and three-dimensional structure of the bunyavirus NP and the research progress of NP as an antiviral target, in order to provide a theoretical basis for the prevention and treatment of the bunyavirus disease.

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ² test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.
Blood Loss, Surgical ; Carcinoma, Hepatocellular/surgery* ; Female ; Hemorrhage ; Hepatectomy/methods* ; Humans ; Hypertension, Portal/surgery* ; Liver Failure ; Liver Neoplasms/surgery* ; Male ; Retrospective Studies ; Treatment Outcome

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Proteasome regulatory particles(RPs) play a vital role in many essential signaling pathways for the regulation of protein degradation and maintenance of cell homeostasis. The mechanism of eukaryotic proteasomes in cancer treatment and drug development has attracted widespread attention. Currently, three proteasome inhibitors are already in use in clinical treatments. There is continuous in-depth research on proteasome structures as well as functions using crystallography and cryo-electron microscopy. Recently, the atomic structure of three types of RPs has been resolved. Type 1 is conservative RP 19S (PA700). Type 2 is the 11S RP PA28 (PA28α, PA28β, PA28γ) and PA26. Type 3 is a conservative Blm10/PA200 proteasome RP. The Type 1 proteasome RP carries out protein degradation activity in an ATP-dependent manner, types 2 and 3 function in an ATP-independent manner. By studying the structure and function of three different types of proteasome RPs, the mechanism of proteasome activity was clarified and the development of inhibitors based on the structure was promoted. Based on the structural biology research of proteasome RPs, this article systematically summarizes the structural biological characteristics of the three types of proteins and the research progress of their mechanisms of regulation of different cellular processes. This will increase our knowledge about proteasome research developments and will provide important reference information for drug design in cancer treatment.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

Objective To analyze and summarize the imaging features of hepatic epithelioid hemangioendothelioma (EHE).Methods The retrospective and descriptive study was conducted.The clinicopathological data of 9 patients with EHE who were admitted to the Cancer Hospital of Chinese Academy of Medical Sciences between June 2012 and June 2016 were collected.Patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations.Number,size,location,shape,density or signal and enhancement method of lesions,with or without lesions fusion and relationship between lesions and vessels were analyzed by 2 imaging doctors.Lesions in left lobe of liver,right lobe of liver and caudate lobe of liver were respectively counted.Real number was a standard as less than 5 lesions and more than or equal to 5 lesions was represented as ≥ 5.Observation indicators:(1) overall imaging features of EHE;(2) MRI findings of EHE;(3) CT findings of EHE;(4) treatment and pathological features of EHE and results of follow-up.Patients received the corresponding treatment after imaging examinations.Follow-up using outpatient imaging examinations was performed to detect tumor recurrence and stable condition of patients up to December 2016.Results (1) Overall imaging features of EHE:of 9 patients with EHE,6 received plain and enhanced scans of MRI,3 received plain and enhanced scans of CT (1 combined with MRI),1 received enhanced scan of CT.Lesions in right lobe of liver were more than that in left lobe of liver,and there were fewest lesions in caudate lobe of liver.Lesions were round or similar-round shape,with a maximum diameter of 2.5-6.1 cm and an average diameter of 3.6 cm.Four patients had total 2-5 lesions and less than 5 lesions in each lobe of liver,without lesions fusion,including 1 with halo sign and capsule retraction sign and 1 with halo sign.Of other 5 patients,2 had more than or equal to 5 lesions in each lobe of liver and 3 had more than or equal to 5 lesions in 2 lobes of liver;4 had halo sign,lollipop sign,capsule retraction sign and a tendency of lesions fusion,1 had halo sign and capsule retraction sign.The halo sign,lollipop sign,capsule retraction sign and a tendency of lesions fusion were 7/9,4/9,6/9 and 4/9 in 9 patients,respectively.(2) MRI findings of EHE:6 patients received plain and enhanced scans of MRI.① Four patients had clearhalo sign on T2 weighted imaging (T2WI),in portal vein phase and hepatobiliary phase.Three patients had slightly central hyperintensity and thick ring of slightly peripheral hyperintensity on T2WI.There were slightly central hyperintensity and thin ring of slightly peripheral hypointensity in 1 patient,and the halo sign was seen by enhanced scan.There were central hyperintensity and peripheral hypointensity in 2 patients,and the halo signs were clearly seen in hepatobiliary phase.Some patients were combined with multiple manifestations.② There were no obvious halo sign on T2WI,annular enhancement in arterial phase by enhanced scan,no obvious halo sign in portal vein phase and hepatobiliary phase in 2 patients.There were hypointensity on T1WI and isointensity-hyperintensity on DWI in 6 patients.(3) CT findings of EHE:plain scan of CT in 4 patients showed slightly hypodense shadow,without calcification.Enhanced scan of CT in 3 patients showed that obvious halo-like enhancement was seen in portal vein phase and halo rings were less obvious than that by MRI examination.(4) Treatment and pathological features of EHE and results of follow-up:of 9 patients with EHE,4 underwent surgical resection based on lesions ≤5 and surgical specimens were detected by pathological examination,5 underwent interventional treatment and pathologic examination with biopsy.Gross specimen examination showed that lesions were solid and stiff,with greyish white section plane and infiltrative margin.Tumor cells consisted of epithelioid cells under the microscopy,without atypia and with rare mitotic figures,and vacuoles were seen in cytoplasm.Immunohistochemistry showed CD31 and CD34 were positive.Nine patients were followed up for 6-54 months.During the follow-up,4 patients with surgery had no recurrence and 5 patients with interventional therapy remained stable condition.Conclusions Imaging manifestations of hepatic EHE are the more typical when lesions of EHE became more.Hepatic EHE has a tendency of lesion fusion,halo sign,capsule retraction sign and lollipop sign.Imaging manifestations on T2WI with fat suppression,in portal vein phase and hepatobiliary phase are helpful to improve the diagnosis of hepatic EHE.

Background:For Chinese patients with hepatocellular carcinoma (HCC),surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor,and yet the prognosis after surgery is diverse.We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation.Methods:A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital.Age,hepatitis B surface antigen,hepatitis B e antigen,partial thromboplastin time,total bilirubin,alkaline phosphatase,γ-glutamyltransferase,α-fetoprotein,tumor size,cirrhosis,vascular invasion,differentiation,encapsulation,and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion.The Harrell's concordance index (C-index) was used to measure model performance.Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient.Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012,808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010,and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts.Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.Results:Shanghai Score showed good calibration and discrimination in postsurgical HCC patients.The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients),and in the three independent validation cohorts,the CIs for OS ranged 0.70-0.72 and that for RFS ranged 0.63-0.68.Furthermore,Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α).The identified subset of patients at low risk could be ideal candidates for curative surgery,and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery.Finally,a web server with individualized outcome prediction and treatment recommendation was constructed.Conclusions:Based on the largest cohort up to date,we established Shanghai Score-an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery.The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.

OBJECTIVETo investigate the capability of semi-quantitative and quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the response to concurrent chemoradiotherapy( CCRT) in patients with non-small cell lung cancer (NSCLC).

METHODSA total of 24 patients with stage III or IIIB NSCLC, who underwent 3.0T DCE-MRI before CCRT, were enrolled in this study. Semi-quantitative and quantitative parameters were calculated by Funtool and Omnikinetics software. The relationship between these obtained parameters and tumor response was evaluated by Spearmen' s correlation analysis. The patients were classified into two groups according to the tumor regression rate after treatment, as response group (group A) and non-response group ( group B). Mann-Whitney U test was used to compare the parameters of responders and non-responders. The value of the parameters on predicting response was calculated by receiver operating characteristic curve (ROC).

RESULTSThe tumor regression rate after treatment was negatively correlated with time to peak (TTP) and the extravascular-extracellular volume fraction (Ve), and was positively correlated with signal enhancement ratio (SERmax) and volume transfer constant (Ktrans) (P < 0.05 for all). Statistical significant differences were found between group A and group B both in semi-quantitative and quantitative parameters (P < 0.05). Group A had a lower TTP value [(34.66 ± 16.37) s vs. (44.09 ± 17.41) s] and Ve value [(0.19 ± 0.03) vs. (0.25 ± 0.05)] than group B, whereas group A had a higher SERmax [(166.50 ± 44.95)% vs. (113.57 ± 46.62)%] and Ktrans [(0.41 ± 0.17) min(-1) vs. (0.28 ± 0.12) min(-1)] than group B (P < 0.05 for all). The ROC analysis indicated that when setting the threshold of Ve on ≤ 0.21 for predicting response, the specificity, sensitivity and accuracy were 85.7%, 80.0% and 83.3%, respectively, with an area under curve of 0.875 (P < 0.001).

CONCLUSIONSBoth the semi-quantitative and quantitative DCE-MRI parameters are helpful for predicting the response after CCRT of NSCLC. Quantitative parameters seem to be more meaningful than semi-quantitative parameters.

Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Chemoradiotherapy ; methods ; Contrast Media ; Humans ; Lung Neoplasms ; pathology ; therapy ; Magnetic Resonance Imaging ; methods ; ROC Curve ; Remission Induction ; Sensitivity and Specificity ; Time Factors