Objective:To establish a method for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood by ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) .Methods:In October 2022, 200 μl of blood samples were taken and 800 μl of acetonitrile was added. The samples were centrifuged at 3500 r/min (with a centrifugation radius of 6.6 cm) for 15 minutes. The supernatant was detected in the positive ion target tandem mass spectrometry (Target MS 2) mode and quantified by the external standard method. Methodological validation was also carried out for the established method. Results:The working curve of 2-amino-5-chloro-N, 3-dimethylbenzamide showed good linearity in the concentration range of 2.07-165.44 μg/L, with a correlation coefficient ( r) of 0.9994. The intra-day and inter-day relative standard deviations ( RSD) for the detection of 2-amino-5-chloro-N, 3-dimethylbenzamide were 2.6%-3.0% and 3.1%-3.5%, respectively. Analytical accuracy of 2-amino-5-chloro-N, 3-dimethylbenzamide quantification ranged from 101.0 % to 108.4 %, and the limit of detection and limit of quantification were 0.11 μg/L and 0.36 μg/L, respectively. The blood samples were able to be stored at -20 ℃ for at least 7 days. Conclusion:The UPLC-Q-Orbitrap HRMS determination method is sensitive, efficient and accurate, and can be used for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood.

Objective:To establish a method for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood by ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) .Methods:In October 2022, 200 μl of blood samples were taken and 800 μl of acetonitrile was added. The samples were centrifuged at 3500 r/min (with a centrifugation radius of 6.6 cm) for 15 minutes. The supernatant was detected in the positive ion target tandem mass spectrometry (Target MS 2) mode and quantified by the external standard method. Methodological validation was also carried out for the established method. Results:The working curve of 2-amino-5-chloro-N, 3-dimethylbenzamide showed good linearity in the concentration range of 2.07-165.44 μg/L, with a correlation coefficient ( r) of 0.9994. The intra-day and inter-day relative standard deviations ( RSD) for the detection of 2-amino-5-chloro-N, 3-dimethylbenzamide were 2.6%-3.0% and 3.1%-3.5%, respectively. Analytical accuracy of 2-amino-5-chloro-N, 3-dimethylbenzamide quantification ranged from 101.0 % to 108.4 %, and the limit of detection and limit of quantification were 0.11 μg/L and 0.36 μg/L, respectively. The blood samples were able to be stored at -20 ℃ for at least 7 days. Conclusion:The UPLC-Q-Orbitrap HRMS determination method is sensitive, efficient and accurate, and can be used for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood.

Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat.This raises an urgent need for the devel-opment of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14 (NSP14)carrying RNA cap guanine N7-methyltransferase and 3'-5'exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7％ of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy (AG) was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model were-37.2711 ± 3.2160,-30.1746 ± 3.1914,-23.8953 ± 4.4800,and-34.1350 ± 4.3683 kcal/mol,respectively,while the calculated binding free energies were-60.2757 ± 4.7708,-30.9955 ± 2.9975,-46.3099 ± 3.5689,and-59.8104 ± 3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Objective: To analyze the epidemiological characteristics of rotavirus in children under 5 years old in China (excluding China Hong Kong, Macau and Taiwan data, the same below) from 2005 to 2018. Method: Data on other infectious diarrhea in the country from 2005 to 2018 were downloaded from the National Notifiable Disease Report System was to build a database for report cases of rotavirus diarrhea in children under 5 years of age, and descriptive epidemiological methods were used to analyze the data. Result: In 2005-2018, a total of 820 588 cases of rotavirus infection in children under 5 years old were reported nationwide, with male 500 944 cases, and with an average annual incidence of 63.7/100 000. The reported incidence showed a fluctuating upward trend increased from 8.4/100 000 to 178.1/100 000. The number of reporting provinces increased from 17 to 30. The reported incidence showed a peak of season from November to following February. The reported cases of rotavirus diarrhea in children under 5 months of age was 13.1%(107 845 cases), and the high-incidence age ranged from 6 months to 2 years old, accounting for 70.3% (576 874 cases), with a peak of 11-13 months (163 947 cases). The top three provinces (cities) reporting the incidence rate were Zhejiang (535.2/100 000), Guangdong (334.3/100 000) and Beijing (317.3/100 000), the provinces with the low reported case rates were Shanxi (0.9/100 000), Heilongjiang (1.6/100 000) and Liaoning (2.5/100 000), but there was no case reported in Tibet; The report cases of south region (745 526 cases) were 9.9 times north region (74 935 cases).The cases of rotavirus infection and other diarrhea pathogens were detected simultaneously accounted for 1.8% (15 030 cases) and mainly were positive for rotavirus and adenovirus (90.1%, 13 544 cases). Conclusion The rate of rotavirus infection in children has increased rapidly since the age of 6 months, and 84.4% of the reported cases were infants before the age of 2 years.

Purpose: The systemic inflammation response index (SIRI) has been reported to have prognostic ability in various solid tumors but has not been studied in gallbladder cancer (GBC). We aimed to determine its prognostic value in GBC. Materials and Methods: From 2003 to 2017, patients with confirmed GBC were recruited. To determine the SIRI’s optimal cutoff value, a time-dependent receiver operating characteristic curve was applied. Univariate and multivariate Cox analyses were performed for the recognition of significant factors. Then the cohort was randomly divided into the training and the validation set. A nomogram was constructed using the SIRI and other selected indicators in the training set, and compared with the TNM staging system. C-index, calibration plots, and decision curve analysis were performed to assess the nomogram’s clinical utility. Results: One hundred twenty-four patients were included. The SIRI’s optimal cutoff value divided patients into high (≥ 0.89) and low SIRI (< 0.89) groups. Kaplan-Meier curves according to SIRI levels were significantly different (p < 0.001). The high SIRI group tended to stay longer in hospital and lost more blood during surgery. SIRI, body mass index, weight loss, carbohydrate antigen 19-9, radical surgery, and TNM stage were combined to generate a nomogram (C-index, 0.821 in the training cohort, 0.828 in the validation cohort) that was significantly superior to the TNM staging system both in the training (C-index, 0.655) and validation cohort (C-index, 0.649). Conclusion The SIRI is an independent predictor of prognosis in GBC. A nomogram based on the SIRI may help physicians to precisely stratify patients and implement individualized treatment.

Objective: To investigate the epidemiological characteristics of norovirus clustering and outbreaks in schools and kindergartens in China, so as to provide references for prevention and control of outbreaks. Methods: A descriptive epidemiological method was used to analyze outbreaks of Norovirus in schools and kindergartens in China during 2014-2018 , the indicators which was analyzed and compared including attack rate, duration of the outbreak, reporting interval. Results: A total of 832 Norovirus outbreaks were reported by schools and kindergartens in China from 2014 to 2018. The total number of outbreaks showed an upward trend with an average annual growth rate of 58%. The number of reported cases was 40 445 but there was no death. Norovirus outbreaks mainly occurred in primary schools (42%), followed by kindergartens and middle schools (both 24%), university (6%) and 77 outbreaks (4%) were reported in universities and other schools. The peak seasons were March to May, November and December each year. Jiangsu Province and Guangdong Province (both 22%) reported the largest number of outbreaks. The main transmission of norovirus outbreaks was through direct person contact (72%), foodborne (4%) and waterborne (3%) caused fewer outbreaks than direct person contact. The duration of the epidemic was positively correlated with the reporting interval (r=0.63, P<0.05) and the number of cases per outbreak (r=0.51, P<0.05). Conclusion Disinfection treatment of vomitus should be standardized in schools and kindergartens. Timely detection, reporting, disposal of the epidemic can effectively control the spread of norovirus outbreaks.

Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

Hepatic hemangioma is a common benign tumor of liver,while hepatic hemangioma with a diameter ＞ 3 cm is rarely seen in clinical practice.A female patient with a giant hepatic hemangioma (diameter =48 cm) received tumor resection via chest and abdomen joint incision at the Peking Union Medical College Hospital on April 10,2012.The patient received exploratory laparotomy for hepatic tumor via chest and abdomen joint incision 22 years ago,while the operation was failed due to intraoperative bleeding.The success of the operation benefited from comprehensive application of computed tomography angiography reconstruction technique,three-dimensional liver reserve function assessment,intraoperative controlled low central venous pressure,total hepatic vascular exclusion and precise hepatectomy technique.

Objective To summarize the clinical diagnosis and treatment of nodular regenerative hyperplasia of the liver. Methods Retrospective analysis was made on the clinical manifestations,imagings, laboratory tests, diagnosis, treatment and prognosis of 18 consecutive cases finally established as NRH during the past 26 years. Results 15 of the 18 cases showed portal hypertension, 4 cases showed mono or multiple occupations of the liver, 8 cases suffered from concurrent autoimmune diseases, 3 cases were suspected of blood diseases. Preoperatively, 13 cases were diagnosed as cirrhosis, 2 cases were diagnosed as liver cancer or focal nodular hyperplasia ( FNH). All cases were diagnosed by operative wedging biopsy. 3 cases received splenectomy, 4 cases received disconnection /Phemister surgery, 3 cases received liver occupation/liver lobe resection, 1 case received partial small bowel resection, and 1 case received spleen artery restrictive surgery. Postoperatively, symptoms of portal hypertension relieved obviously. Follow-up study showed most of the patients were stable and prognosis of the NRH was good.Conclusions NRH may relate to the disturbance of liver blood supply, and most common clinical manifestation is portal hypertension, and can combine with immune diseases, hematopathy also can present single or multiple liver occupations. Differential diagnoses include liver cirrhosis, FNH, idiopathic portal hypertension. Diagnosis of NRH relies on liver wedging biopsy. Surgery can relive concurrent portal hypertension.