1.Advances in targeted therapy for gastric cancer based on tumor driver genes
Shiying WU ; Pinglong XU ; Fei ZHANG
Journal of Zhejiang University. Medical sciences 2024;53(1):73-83
As the understanding of the pathogenic mechanisms of gastric cancer deepens and the identification of gastric cancer driver genes advances,drugs targeting gastric cancer driver genes have been applied in clinical practice.Among them,trastuzumab,as the first targeted drug for gastric cancer,effectively inhibits the proliferation and metastasis of tumor cells by targeting overexpressed human epidermal growth factor receptor 2(HER2).Trastuzumab has become the standard treatment for HER2-positive gastric cancer patients.Ramucirumab,on the other hand,inhibits tumor angiogenesis by targeting vascular endothelial growth factor receptor 2(VEGFR2)and has been used as second-line therapy for advanced gastric cancer patients.In addition,bemarituzumab targets overexpressed fibroblast growth factor receptor 2(FGFR2),while zolbetuximab targets overexpressed claudin 18.2(CLDN18.2),significantly extending progression-free survival and overall survival in patients with gastric cancer in clinical trials.This article reviews the roles of tumor driver genes in the progression of gastric cancer,and the treatment strategies for gastric cancer primarily based on targeting HER2,VEGF,FGFR2,CLDN18.2 and MET.This provides a reference for clinical application of targeted therapy for gastric cancer.
2.Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023).
Yuanyuan MI ; Zheyi CAI ; Jing LIU ; Fei TIAN ; Liping YANG ; Lei BAO ; Shanbing HOU ; Su GU ; Li LI ; Xueli ZHOU ; Yun XU ; Shumei ZHANG ; Xiaoxia FU ; Xiaodi LI ; Chuansheng LI ; Liang SUN ; Xiaohong ZHANG ; Hong QI ; Shiying YUAN ; Liqun ZHU ; Haiyan HUANG ; You SHANG
Chinese Critical Care Medicine 2023;35(4):337-351
The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
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3.Establishment and validation of a nomogram model for predicting malignant cerebral edema in elderly patients with acute large hemispheric infarction of the anterior cerebral artery
Yumei WANG ; Geman XU ; Xiaoming MA ; Wei XIE ; Liping CAO ; Mengmeng WANG ; Shiying SHENG ; Meng LIU
Chinese Journal of Geriatrics 2023;42(11):1273-1279
Objective:To construct and validate a predictive model for the occurrence of malignant cerebral edema(MCE)in the elderly with acute large hemispheric infarction(LHI)of the anterior cerebral artery.Methods:Clinical, laboratory and imaging data of 301 elderly patients with acute LHI of the anterior cerebral artery admitted to the Department of Neurology of the Third Affiliated Hospital of Soochow University between January 2018 and April 2023 were retrospectively analyzed.Patients were divided into a modeling group(211 cases)and a validation group(90 cases)by the simple random sampling method with a ratio of 7∶3.According to the occurrence of MCE, univariate and multivariate Logistic regression analyses were performed with data from the modeling group to screen for independent predictors of the development of MCE.Nomograms were created and internally validated using R software.Additionally, external validation was performed with data from the validation group, and the performance of the model was assessed by receiver operating characteristic(ROC)curves, calibration plots, and clinical decision curve analysis(DCA), respectively.Results:The MCE incidence and baseline data between the modeling and validation groups were not statistically significantly different and were actually comparable.Multivariate Logistic analysis in the modeling group showed that a history of atrial fibrillation( OR=3.459, 95% CI: 1.202-9.955, P=0.021), Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score( OR=1.202, 95% CI: 1.052-1.373, P=0.007), National Institutes of Health Stroke Scale(NIHSS)score( OR=1.163, 95% CI: 1.039-1.3013, P=0.008), Alberta Stroke Program Early CT Score(ASPECTS)( OR=0.782, 95% CI: 0.639-0.958, P=0.018), and collateral score(CS)( OR=0.414, 95% CI: 0.221-0.777, P=0.006)were independent predictors of the occurrence of MCE in the elderly patients with LHI.Based on the nomogram model constructed using the independent predictors, the ROC value for the risk of developing MCE was 0.912(95% CI: 0.867-0.957)in the modeling group and 0.957(95% CI: 0.902-0.997)in the validation group.The predicted probabilities from the nomograms in the modeling and validation groups were close to the actual probabilities, indicating good calibration.The DCA curves in the validation group showed that the predictive model had good clinical utility. Conclusions:The nomogram model established in this study exhibits good discrimination and calibration for the prediction of MCE, and has some predictive value.
5.Ubiquitin-specific peptidase 22 (USP22) regulates the level and function of hepatitis B virus X protein
Shiying ZHOU ; Qiong WU ; Yi ZHANG ; Lu ZHANG ; Xu LIN ; Wannan CHEN
Chinese Journal of Microbiology and Immunology 2022;42(6):434-442
Objective:To investigate the effects of the interaction between ubiquitin-specific peptidase 22 (USP22) and hepatitis B virus X protein (HBx) on the protein level and the biological function of HBx.Methods:The interactions between HBx and USP22 were analyzed by GST pull-down, co-immunoprecipitation assay and confocal laser scanning assay. USP22 recombinant plasmids or specific siRNA were transiently co-transfected with HBx plasmids. Western blot were used to detect the protein level of HBx. The half-life and degradation pathway of HBx in the transfected cells treated with cycloheximide (CHX) or proteasome inhibitor MG132 were detected. In vivo ubiquitination assay was used to detect the ubiquitination of HBx with USP22 overexpression. Moreover, dual-luciferase reporter assay and colony formation assay were used to analyze the effects of USP22 on the biological function of HBx. Results:USP22 could interact with HBx in vivo and in vitro. USP22 significantly increased the stability of HBx and inhibited the proteasome-mediated degradation of HBx protein by reducing the ubiquitination of HBx, thereby enhancing the biological function of HBx. Conclusions:USP22 inhibited HBx protein degradation through ubiquitin-dependent proteasome pathway, thus enhancing the stability and biological function of HBx.
6.Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition)
Yuanyuan MI ; Haiyan HUANG ; You SHANG ; Xiaoping SHAO ; Peipei HUANG ; Chenglin XIANG ; Shuhua WANG ; Lei BAO ; Lanping ZHENG ; Su GU ; Yun XU ; Chuansheng LI ; Shiying YUAN
Chinese Critical Care Medicine 2021;33(8):903-918
Enteral nutrition plays an irreplaceable role in the nutritional treatment of critically ill patients. In order to help clinical medical staff to manage the common complications during the implementations of enteral nutrition for critically ill patients, the consensus writing team carried out literature retrieval, literature quality evaluation, evidence synthesis. Several topics such as diarrhea, aspiration, high gastric residual volume, abdominal distension, etc. were assessed by evidence-based methodology and Delphi method. After two rounds of expert investigations, Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition) developed, and provided guidance for clinical medical staff.
7. Correlation analysis between Dx-pH monitoring and proton pump inhibitor test in the diagnosis of laryngopharyngeal reflux disease
Zhiling CHEN ; Huawei WU ; Xianwei MEI ; Wenhua YIN ; Shiying XU ; Suqin LIU ; Yanchun CHEN ; Gan WANG ; Chenjia ZHANG ; Xiaolong DING ; Jiani WU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2020;55(1):34-39
Objective:
The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated.
Methods:
Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check.
Results:
(1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (
8.Distributions and drug resistance to bacterial pathogens in children with community acquired pneumonia in Shanghai
Juan XU ; Yong YIN ; Lixia ZHAO ; Fengjuan JI ; Yajuan ZHOU ; Lei ZHU ; Shiying LIU
Chinese Journal of Applied Clinical Pediatrics 2018;33(16):1246-1250
Objective To investigate the distribution and drug resistance to pathogenic bacterial pathogen in children with community acquired pneumonia (CAP),so as to provide recommendations for clinical rational use of anti-biotics. Methods A retrospective analysis was made on the distribution and drug resistance to bacteria in CAP chil-dren admitted to Department of Respiration,Shanghai Children′s Medical Center from January 2014 to December 2015. Results There were 463 patients with positive sputum culture,and a total of 496 strains of pathogens were found. There were 273 Galanz negative bacteria,195 Galanz positive bacteria and 28 other rare bacteria,accounted for 55. 04%,39. 31% and 5. 65% of the total bacteria,respectively. The main pathogens were Streptococcus pneumoniae, Staphylococcus aureus,Haemophilus influenzae,Klebsiella pneumoniae and Escherichia coli. The highest detection rate of bacteria in 1-12 months children with CAP was Staphylococcus aureus,Klebsiella pneumoniae and Escherichia coli;in > 12 months children with CAP,the highest detection rate of bacteria was Streptococcus pneumoniae,Haemophilus influenzae and Staphylococcus aureus. Both of Streptococcus pneumoniae and Staphylococcus aureus had a high resis-tance to Erythromycin,Clindamycin and Oxacillin. There were 11. 00% Streptococcus pneumoniae and 94. 74% taphy-lococcus aureus resistant to Penicillin,while they were not resistant to Vancomycin. Escherichia coli and Klebsiella pneumoniae both showed a high resistance to ampicillin,the second and third generation cephalosporins. Haemophilus influenzae were highly resistant to Compound sulfamethoxazole and Ampicillin. Galanz negative bacteria had the lowest resistance to Piperacillin/ Tazobactam and Amikacin. Conclusions The main pathogens of CAP in children were G -bacteria. There were some differences among the isolates at different ages of CAP. Their resistance to very common anti-biotics was very high in children.
9.Investigation on the Use of Oral High-risk Tablets in Hospitalized Patients in a Children's Hospital in Shanghai
Shiying HUANG ; Fanghong SHI ; Hao LI ; Shunguo ZHANG ; Wei ZHAO ; Xuexian WANG ; Anle SHEN ; Bulong XU ; Minling CHEN
China Pharmacist 2018;21(2):257-260
Objective:To analyze the dosage distribution and the frequency of each dosage of high-risk tablets in the hospitalized patients in a children's hospital,and study whether the existing specifications of high-risk tablets meet the pediatrics clinical needs. Methods:All the prescriptions including high risk tablets were analyzed from 2014 to 2016 in Shanghai children's medical center. The frequency of every dosage of every drug was analyzed,and the current specifications were judged according to the frequency. New specifications were proposed when the existing specifications did not match the clinical needs. The new frequency of the proposed speci-fications was re-accounted for all the three-year prescriptions in order to evaluate whether the proposed new specifications met the clini-cal needs. Results:Among the five kinds of high-risk oral tablets,methotrexate tablets and vitamin A acid tablets were in accordance with the actual clinical requirements. Mercaptopurine tablets should add two specifications including 12.5 mg and 17 mg,and warfarin sodium tablets should add one specification(1.25 mg). Hydroxyurea tablets(250 mg) and warfarin sodium tablets(1 mg) were rec-ommended used in the children's hospital. Conclusion:The existing specifications of high-risk oral tablets can't fully meet the clini-cal needs,therefore,specifications still needs to be adjusted.
10.Clinical features of cholestatic liver disease of 107 cases
Xin XU ; Yichen DAI ; Shiying XUAN
Journal of Clinical Hepatology 2018;34(11):2364-2367
ObjectiveTo investigate the clinical features of cholestatic liver disease (CLD), and to provide a reference for strengthening the diagnosis and treatment of this disease. MethodsA retrospective analysis was performed for the clinical data of 107 patients who were admitted to Chenggong Hospital Affiliated to Xiamen University from January 2015 to December 2017 and were diagnosed with CLD. The t-test was used for comparison of continuous data between groups. ResultsMost patients had the clinical symptoms of weakness, loss of appetite, nausea, abdominal distension, pruritus, and jaundice. According to the site of cholestasis, there were 64 patients (59.8%) with intrahepatic cholestasis and 43 (40.2%) with extrahepatic cholestasis. The cause of the disease was common bile duct stones in 21 patients (19.6%), bile duct parasites in 1 patient (0.9%), primary sclerosing cholangitis in 2 patients (1.9%), primary biliary cirrhosis in 3 patients (2.8%), liver cancer in 8 patients (7.5%), bile duct carcinoma in 5 patients (4.7%), pancreatic cancer in 4 patients (3.7%), pancreatitis in 12 patients (11.2%), viral hepatitis in 28 patients (26.2%), drug-induced liver injury in 11 patients (10.3%), alcoholic hepatitis in 6 patients (5.6%), nonalcoholic fatty liver disease in 4 patients (3.7%), and autoimmune hepatitis in 2 patients (19%). The CLD patients with underlying diseases had a significantly poorer liver function (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, bile acid, and total bilirubin) than those with CLD alone (t=-3.44, -2.99, -2.42, -4.39, -3.34, and -2.49, all P<0.05). Most of the patients achieved good recovery after liver-protecting, transaminase-lowering, and jaundice clearance treatment. The patients with tumors had poor prognosis. ConclusionCLD has various causes, and its clinical features lack specificity. Clinicians should pay enough attention to this disease.

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