Research advances in transcatheter arterial chemoembolization combined with targeted agents or anti-PD-1/PD-L1 monoclonal antibody in treatment of patients with unresectable hepatocellular carcinoma / 临床肝胆病杂志

Transcatheter arterial chemoembolization (TACE) is recommended by domestic and international guidelines for the treatment of patients with unresectable hepatocellular carcinoma (uHCC), and it is one of the most common treatment methods for patients with uHCC. The chemotherapy drugs commonly used in TACE for HCC include epirubicin, cisplatin, and fluorouracil, while it is still unclear which chemotherapy drug has a better clinical effect. This article summarizes the studies of different TACE regimens using different chemotherapy drugs in the treatment of patients with uHCC in the recent five years. TACE combined with sorafenib can significantly improve the survival of patients with advanced HCC and has been recommended for the treatment of such patients by Chinese Society of Clinical Oncology guidelines, and the efficacy of TACE combined with other tyrosine kinase inhibitors (TKI) has become a research hotspot. Studies have shown that compared with TACE combined with sorafenib in the treatment of patients with advanced HCC, TACE combined with lenvatinib can achieve a significantly longer progression-free survival time and a tendency of increase in median overall survival time. However, due to the variation of target receptors or downstream signals, resistance to molecular-targeted agents is still a challenging problem. TKI combined with immune checkpoint inhibitors may be a promising strategy for the treatment of patients with uHCC. Some studies suggest that triple therapy using TACE combined with TKIs and anti-PD-1/PD-L1 monoclonal antibody has better efficacy in improving the survival of patients with uHCC. This article reviews the studies of the efficacy and safety of TACE combined with targeted agents and TACE combined with anti-PD-1/PD-L1 monoclonal antibody in the treatment of patients with uHCC in the recent five years.

Development of acute－on－chronic liver failure in progressive chronic liver diseases： Risk prediction and stratified management / 临床肝胆病杂志

Patients with advanced chronic liver disease （ACLD） are hospitalized due to hepatitis， acute decompensation or liver failure and its complications， and they often require stratified management due to different severities. The patients with acute－on－chronic liver failure （ACLF） have the highest short－term mortality rate among ACLD patients and should be treated in tertiary hospitals. Although non－ACLF patients tend to have a relatively low mortality rate， they still have the risk of progression to ACLF， and there is a significant increase in mortality rate after progression to ACLF， which requires stratified management. The patients with extremely low progression rates often have favorable clinical outcomes and can be administrated in primary hospitals， while the high－risk population should be closely monitored and timely transferred in case of disease progression. However， currently there is still a lack of accurate predictive models for evaluating the risk of progression to ACLF， and further studies are needed to find new biomarkers or algorithms.

Noninvasive screening and management of cirrhotic portal hypertension / 临床肝胆病杂志

Portal hypertension-related complications are the major cause of death in patients with advanced chronic liver disease (ACLD). Hepatic venous pressure gradient is the golden standard for assessing portal hypertension, and upper gastrointestinal endoscopy is an important method for screening and assessing esophageal and gastric varices and its severity; both methods are invasive and inappropriate for portal hypertension screening and monitoring. Noninvasive approaches, such as transient elastography, acoustic radiation force impulse, and shear wave elastography, have been used for the evaluation of portal hypertension in ACLD patients, especially the screening, stratified diagnosis, and monitoring of clinically significant portal hypertension.

Advances and challenges in cirrhotic portal hypertension: A new start from the Baveno Ⅶ consensus / 临床肝胆病杂志

The new consensus on portal hypertension issued by Baveno Cooperative Group, i.e., the Baveno Ⅶ consensus, summarizes the diagnostic criteria for portal hypertension, noninvasive screening and diagnosis, primary prevention including etiological treatment and non-etiological treatment, secondary prevention including endoscopy and vascular intervention for diagnosis and treatment, new concepts associated with decompensated liver cirrhosis, and major advances and research agenda for the research directions including liver vascular diseases. Baveno Ⅶ consensus has an important reference value for clinical practice and research in the related fields of portal hypertension in China. As a part of the special issue, this article briefly describes the advances and challenges in portal hypertension in China from the perspective of clinical practice.

A novel cell tool for α2δ-1-NMDAR target-based analgesic drug discovery / 生物工程学报

The α2δ-1 protein coded by Cacna2d1 is dramatically up-regulated in dorsal root ganglion (DRG) neurons and spinal dorsal horn following sensory nerve injury in various animal models of neuropathic pain. Cacna2d1 overexpression potentiates presynaptic and postsynaptic NMDAR activity of spinal dorsal horn neurons to cause pain hypersensitivity. The α2δ-1-NMDAR interaction promotes surface trafficking and synaptic targeting of NMDARs in neuropathic pain caused by chemotherapeutic agents and peripheral nerve injury, as well as in other pathological conditions such as in the paraventricular nucleus (PVN) with neurogenic hypertension and in the brain with ischemic stroke. The lentiviral transfection method was used to construct a human embryonic kidney HEK293T cell line that could stably express α2δ-1-NMDAR complex. A stably transfected cell line was observed by florescence microscope, and identified by RT-qPCR and Western blotting. The results showed that the HEK293T cell line was successfully transfected and the genes could be stably expressed. Subsequently, the transfected cell line was successfully developed into a target drug screening system using patch clamp techniques. It provides a promising cell model for further research on the interaction mechanism of α2δ-1-NMDAR complex and drug screening for chronic pain and related diseases with low side effects.

Changes in hemostasis and clinical significance of coagulation function test in patients with liver cirrhosis / 临床肝胆病杂志

The liver plays an important role in procoagulant and anticoagulant mechanisms in human body. There are complex changes in hemostasis in patients with liver cirrhosis, with the presence of interaction between the portal venous system and the peripheral system and differences in etiology, and such patients have a dual trend of hemorrhage and thrombosis. At present, there are certain limitations in coagulation function tests commonly used in clinical practice. The primary etiology and results of various coagulation tests should be considered before initiation of anticoagulant therapy for patients with liver cirrhosis, so as to make the best clinical decisions for patients.

Diagnosis and treatment of abdominal infection in patients with liver cirrhosis: Advances and challenges / 临床肝胆病杂志

Infection is the most common complication in patients with end-stage liver disease, among which abdominal infection is the most common type. There is a low positive rate of ascitic fluid culture, and abdominal infection is mainly diagnosed based on multinucleated cell count in ascites and is mainly treated by empirical antimicrobial therapy. The diagnostic criteria for abdominal infection have limited guiding significance in clinical practice, and currently there are still no new diagnostic markers that can be used in clinical practice. For the pathogenic diagnosis of abdominal infection, metagenomic next-generation sequencing is a new technique for rapid identification of pathogens of abdominal infection or overlap infection in liver cirrhosis. In terms of treatment, Chinese guidelines on the management of ascites in cirrhosis emphasize antimicrobial therapy and give no explicit recommendation for the dose of human serum albumin infusion. There are still great challenges in the diagnosis and treatment of abdominal infection in cirrhotic patients, and more studies are needed in the future to answer relevant questions and better guide clinical practice, including the optimization of the diagnosis, prevention, and treatment of abdominal infection.

Application of metagenomic next-generation sequencing in sepsis in liver cirrhosis / 临床肝胆病杂志

Due to persistent systemic inflammation and immunosuppressive conditions, patients with liver cirrhosis are susceptible to bacterial infection, which may progress to sepsis without proper control. Early effective antibiotic therapy is the key to improving the prognosis of patients with sepsis. This article briefly describes the pathophysiological mechanism of sepsis in patients with liver cirrhosis and the current status of the diagnosis and treatment of sepsis, and it is pointed out that metagenomic next-generation sequencing can be used to guide effective antibacterial treatment of sepsis.

Effect of artificial liver support therapy on the short-term prognosis of patients with liver failure in the plateau stage: A stratified analysis based on Model for End-Stage Liver Disease score / 临床肝胆病杂志

ObjectiveTo investigate the effect of artificial liver support therapy on the short-term (28- and 90-day) mortality rate of patients with liver failure in the plateau stage through a stratified analysis based on Model for End-Stage Liver Disease (MELD) score. MethodsA retrospective analysis was performed for 187 patients with liver failure who were admitted to Nanfang Hospital, Southern Medical University, from January 2015 to April 2019, with 73 patients in the artificial liver group and 114 in the non-artificial liver group. The stratified analysis based on MELD score in the plateau stage was performed to investigate the differences in 28- and 90-day mortality rates, hospital costs and length of hospital stay of surviving patients, and incidence rate of adverse reactions of artificial liver support therapy between the two groups. The t-test was used for comparison of continuous data between the two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between the two groups. ResultsCompared with the non-artificial liver group, the artificial liver group had a significant reduction in the 28-day mortality rate of the patients with an MELD score of 30-39 (5.9% vs 39.6%, P＜0.001) or those with an MELD score of 40 (25.0% vs 72.7%, P＜0.05). Compared with the non-artificial liver group, the artificial liver group had a significant reduction in the 90-day mortality rate of the patients with an MELD score of 30-39 (23.5% vs 623%, P＜0.001). Artificial liver support therapy did not significantly shorten the mean hospital stay of the surviving patients (P＞0.05) and had no significant influence on the total hospital costs of the surviving patients within 90 days (P＞0.05). The incidence rate of adverse reactions related to artificial liver support therapy was 29.1%, but the symptoms were mild and were relieved after symptomatic treatment. ConclusionPatients with an MELD score of ＜30 in the plateau stage tend to have low 28- and 90-day mortality rates, and artificial liver support therapy can be reasonably selected according to the patient’s economic conditions and willingness. Artificial liver support therapy is recommended for patients with an MELD score of 30-39 in the plateau stage if there is no obvious contraindication. For patients with an MELD score of 40 in the plateau stage, artificial liver support therapy is recommended within 28 days if there is no obvious contraindication, and liver transplantation is recommended as soon as possible. Artificial liver support therapy has no significant influence on the total hospital costs and mean hospital stay of the surviving patients within 90 days and does not increase the economic burden of patients.

Culture-Positive Spontaneous Ascitic Infection in Patients with Acute Decompensated Cirrhosis: Multidrug-Resistant Pathogens and Antibiotic Strategies

Recombinant expression and purification of spider toxin, JZTX-51 and JZTX-26, from Chilobrachys jingzhao / 生物工程学报

To establish a simple, quick and effective method to get a large amount of spider toxin JZTX-26 (35 aa) and JZTX-51 (27 aa) with 3 disulfide bonds each, the mature peptides coding gene fragments were constructed and fused with maltose-binding protein (MBP) tag in an Escherichia coli expression vector pMAL-p2x. The recombinant constructs pMAL-jz26 and pMAL-jz51 were transformed and cultured in E. coli TB1 and BL21 (DE3). After being induced by isopropyl-β-d-thiogalactoside (IPTG), the periplasmic proteins were purified by amylose affinity chromatography and analyzed by SDS-PAGE. The fusion proteins were digested with factor X, and purified by Sizes-Exclusion chromatography and Reversed Phase HPLC. Molecular weights of the purified peptides were obtained by using a MALDI-TOF-TOF mass spectrometer, which were consistent with the theoretical molecular weights. Five milligram of target protein could be purified from 1 L of culture medium. The results indicate that the peptides with three disulfide bonds can be expressed by using the prokaryotic expression system with MBP tag. Our findings suggest the possibility of genetic engineering to obtain large amount of spider peptide toxins.

Mechanical Shimming Method and Implementation for Permanent Magnet of MRI System / 中国医疗器械杂志

A mechanical shimming method and device for permanent magnet of MRI system has been developed to meet its stringent homogeneity requirement without time-consuming passive shimming on site, installation and adjustment efficiency has been increased.

Clinical characteristics of patients with acute-on-chronic liver failure and splenomegaly / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the clinical characteristics and short-term survival of patients with splenomegaly and acute-on-chronic liver failure related to chronic HBV infection.</p><p><b>METHODS</b>Electronic medical records of patients with acute-on-chronic liver failure were collected to analyze the clinical parameters and 4-week survival of patients with or without splenomegaly.</p><p><b>RESULTS</b>Of the 149 patients enrolled, the overall 28-day mortality rate was 48.3%, which was lower in patients with enlarged spleen than those without (34.2% vs 54.1%, P=0.034). Compared with patients without splenomegaly, patients with splenomegaly had lower platelet counts (P=0.001), lower ALT levels (P=0.005) and lower PT-INR (P=0.010). Although the occurrence of hepatic encephalopathy was comparable between patients with or without splenomegaly, severe conditions were more frequent in those without splenomegaly. Hepatic encephalopathy grades, serum creatinine levels, neutrophil percentages over 70%, PT-INR and splenomegaly were independent factors associated with the 28-day survival, and this novel model was superior to model of end-stage of liver disease in predicting the 4-week survival (P=0.017).</p><p><b>CONCLUSION</b>Patients with splenomegaly that evolves into acute-on-chronic liver failure have unique clinical characteristics and further clinical observations are warranted.</p>

Analysis on clinical diagnosis and treatment in 73 cases of children urethral injury / 重庆医学

Objective To summarize the diagnosis and treatment of urethral injury in children ,and to discuss the effective treat-ment method .Methods The retrospective analysis was performed on the data of 73 cases of children urethral injury in this hospital during recent 10 years .Results 66 cases were male ,7 cases were female ,aged 1-15 years old(average 7 years old) .In the male ca-ses ,there were 8 cases of anterior urethral injury ,10 cases of bulbous urethral injury ,44 cases of posterior urethral injuries and 4 cases of bladder neck injury ;in the female cases ,there were 6 cases of urethral injury and 1 case of bladder neck injury .The once cure rate of urethral realignment was 78 .6% ,which of stageⅠ urethral anastomosis was 80% and which of stage Ⅱurethral repair was 69 .6% .Conclusion Different operation modes have their advantages and disadvantages .The corresponding treatment scheme should be formulated according to the comprehensive assessment of the patient′s general condition and damage types .

Liver separation procedures in two conjoined twins / 中华普通外科杂志

Objective To sum up experience and lessons learnt from liver separation in two thoracoventropagus twins. Method By preoperative imaging it was verified that the two twins of thoracoventropagus named as AB and CD respectively having independent portal hepatic system and the digestive tract.Intraoperatively a separation line was delineated between the porta hepatis,the second porta hepatis.Liver parenchyma of the AB conjoined twin was separated under local blood control with both sides of the seperation line.Intraoperative bleeding was about 10ml,liver rough surface was suctured together,after ligation or suturing of blood vessels and bile ducts.The livers of CD conjoined twin were separated with blocking the first hepatic hilum firstly,and partial hepatic vascular exclusion secondly by part of the liver pressed with finger.There was intraoperative bleeding of about 200 ml. Results The two cases of conjoined twins were separated successfully,and there was no bile leakage,liver failure and infection.A and B are alive and well.D died of lung infection 78 days later.C died of lung and cavitas thoracis infection 9 months later. Conclusion Liver separation is feasible in a thoracoventropagus with independent porta hepatis system.Partial blocking of hepatic vasculature occlusion,in stead of portal triad clamping is preferred.During the separation of hepatic parenchyma finger press for the control of local hepatic blood flow is not always reliable.

The Value of Plasma Brain Natriuretic Peptide in Differentiating Acute Dyspnea from Aged Patients with Heart Failure / 医学研究杂志

Objective To investigate the value of brain natriuretic peptide (BNP) in differentiating acute dyspnea from aged pa-tients with heart failure. Methods The concentration of plasma BNP was measured with immunofluorescence assay in 145 aged patients with dyspnea who admitted to hospital by emergency or were out - patients. Results The BNP level in patients with dyspnea caused by heart failure was significantly higher than that of lung disease patients. BNP for the diagnosis of left heart failure had a very strong predic-tive value, while the early diagnosis of pulmonary heart disease and right heart failure has yet to be explored. BNP values > 100ng / L for differentiating of heart failure was the following: the sensitivity of diagnosis was 94.1%, accuracy 93. I%, specificity 79.5%, positive predictive value was 91.3%, and negative predictive value was 85.4%. Conclusion BNP assay was a convenient, rapid and sensitive method for differentiating diagnosis in aged patients with heart failure, especially with left heart failure. It can be used as an important dif-ferential method in elderly patients with acute dyspnea.

Artificial vessel construction in nude mice by subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells / 中国组织工程研究

BACKGROUND: A lot of researches have proved that polyglicolide acid (PGA), as a stent material, has been successfully used to construct engineered tissues, such as cartilage, bone and tendons, in nude mice or even big mammal. Whether the incubation of vascular endothelial cells and smooth muscle cells in the polyglicolide acid may subcutaneously construct vessel-like structure in nude mice needs a further study.OBJECTIVE: To verify the feasibility of forming vessel-like structure in the nude mice by subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells derived from newborn umbilical vein.DESIGN: Contrast study.SETTING: Tissue Engineering Key Laboratory, Medical College, Shanghai Jiao Tong University.MATERIALS: This study was performed at Tissue Engineering Key Laboratory, Medical College, Shanghai Jiao Tong University from January to June 2002. Belly band was derived from newborn babies in our department of obstetrics & gynecology. The parturien provided the informed consent, and this study was approved by the local research ethics committee. Twenty-six nude mice (3-4 weeks old, clean grade, irrespective of gender) were selected in this study. The animal experiment received confirmed consent from the local ethic committee. Polyglicolide acid was provided by Albany International Research Co.METHODS: Vascular endothelial cells and smooth muscle cells derived from newborn umbilical vein were incubated on a piece of polyglicolide acid to produce cell-material compound. In addition, the compound covered around the silicone tube to form a tube-like structural substance. Subsequently, the tube-like structural substance was subcutaneously implanted in 20 nude mice, which were regarded as an experimental group. And then, polyglicolide acid alone was subcutaneously transplanted in the rest 6 nude mice, which was regarded as a control group.MAIN OUTCOME MEASURES: Gross observations of cell-material compound by 2 and 6 weeks after transplantation;HE staining and immunohistochemical staining.detection; expression of factor Ⅷ and α-smooth muscle actin.RESULTS: Twenty-six nude mice were included in the final analysis. ① Gross observation: At 2 weeks after implantation,both the experimental and control groups formed tubular structures, however, at 6 weeks after implantation, the tubular structure still remained in experimental group but not in the controls. ② Histological observation and immunohistochemical detection: The histological examination of the engineered vessel showed that at 2 weeks, the vessels in both group contained mainly undegraded PGA fibers, while at 6 weeks, the PGA fibers were almost completely degraded in both groups and in the control group only fibrous-like tissue formed. Contrastly, in experimental group a typical vascular structure formed, Masson's trichrome stain, which stains collagen green, smooth muscle fibers red and cells purple, showed significant amounts of stainable collagen and smooth muscle fibers in the wall of the engineered vessel, furthermore,immunohistochemistry examination revealed that there were an endothelial cell layer formed in the inner surface of the engineered vessel which was confirmed by positive staining of yon Willebrand factor, meanwhile, the smooth muscle cells in the wall of the engineered vessel were confirmed by the positive staining of smooth muscle α-actin.CONCLUSION: The subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells may form vessels, which are similar to normal vascular histological structure.

Identification of two newly discovered subgenotypes of hepatitis B virus genotype C / 中华传染病杂志

Objective To analyze the genotypic characteristics of hepatitis B virus (HBV)C/D recombinant of two types of newly discovered HBV genotypea found in Western China.Methods The whole genomes of 17 HBV strains isolated from Western China were amplified by polymerase chain reaction (PCR). Bioinformatic softwares were used for the analysis of full genome structure,genetic distances and recombination points.Results The heterogenicity of the HBV C/D recombinant was more than 8% compared with genotype A,B,D,E or F,but 3.8% 0A-8.O% compared with genotype C Based on phylogenetie analysis, a11 C/D recombinant strains clustered within genotype C.but were rouped into two other clusters within the genotype C independently from C1-C5 subgenotypes,which were two kinds of new HBV/C genotypea.Condusion The HBV C/D recombinant could he considered as tWO kinds of new subgenotypea of HBV genotype C which are different from subgenotype C1-C5 based on the genetic distances analysis.

Study on the risk of infection with SARS-coronavirus in health care workers in the designated hospital exclusively for SARS / 解放军医学杂志

Objective To investigate the risk rate of infection with SARS coronavirus in health care workers in an designated hospital, and to assess the effectiveness of the isolation system in prevention of nosocomial transmission of SARS. Methods Questionnaire was submitted to all health care workers related with SARS patients, and ELISA assay was performed to detect IgG antibody against SARS coronavirus for all of them. Results 450 health care workers were submitted the same questionnaire, 445 questionnaires were returned, and 441 blood samples were collected. It was confirmed that all health care workers involved had complied with the isolation guidelines as formulated by the authority of the hospital. Two hundred and sixty persons out of 441 were classified into the group who had close contact with SARS patients and/or SARS materials. Among these 260 workers, IgG antibody against SARS Coronavirus was detected in 5 of them, who had either worked in the SARS ward, CCU (where 3 SARS probable cases had stayed for a short term), paediatric ward, center for sample transference, or laundry. Therefore, there was no statistically significant difference in the risk rate between the group of workers who had close contact with SARS patients and/or SARS materials and the group without contact. Conclusion The current isolation system against SARS was effective, though might not perfect.

Clinical presentation and pathologic feature of 524 patients with IgA nephropathy / 中华肾脏病杂志

Objective To analyse the incidence, clinical features, histopathology and clinicopathological correlation in different age group of 524 cases with IgA nephropathy(IgAN) retrospectively. Methods 524 cases of IgA nephropathy were divided into three groups according to their age, and the clinical and renal pathological features were analyzed. Results In children group(≤15 years), the incidence of recurrent gross hematuria was 47. 2% and renal impairment 4. 6%. Malignant hypertension as first presentation associated with serious renal impairment occured in 3. 8% patients of youth and adult group (16 - 49 years). Higher incidence of nephrotic syndrome and acute renal failure was found in elder group (50 - 69 years). Conclusions The incidence Of IgAN in children and elder population is increased, especially in the children. They need a further follow-up. For elder patients considered as IgAN, a renal biopsy seems to be necessary. While youths and adults still account for the most part of IgAN patients.