Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To explore the mechanism of anti anxiety (AD) effect of Shenqi Schisandra chinensis using network pharmacology and molecular docking technology.Methods:The main active ingredients of S-Q-W-W-Z (Shenqi Schisandra chinensis) were screened through the TCMSP database. The corresponding targets of the active ingredients were obtained through the TCMSP database and SymMap database. The drug active ingredient target relationship network was visualized using Cytoscape. Utilize TTD, OMIM, NCBI, Drugbank, and GeneCards databases to directly identify potential targets for anxiety. We constructed interaction diagrams of potential targets based on the String database, and used Cytoscape tool to obtain key target proteins. Gene ontology (GO) enrichment analysis and Tokyo Encyclopedia of Genomes (KEGG) signaling pathway analysis were used to identify key targets and signaling pathways for anti anxiety effects of Schisandra chinensis. AutodockTools software was used to perform molecular docking on key active ingredients and key target proteins, and their binding energies were calculated. The molecular docking results were visualized using PyMol software.Results:The 63 effective ingredients in Shen-Qi-Wu-Wei-Zi (Shenqi Schisandra chinensis) can act on anxiety disorder through 69 targets. Among them, quercetin, luteolin, and stigmasterol are the main active ingredients, and serine threonine protein kinase 1 (AKT1) protein and interleukin-6 (IL-6) protein are key target proteins. Molecular docking technology has verified the good binding ability between these key active ingredients and key target proteins. Shenqi Schisandra mainly exerted therapeutic effects on anxiety disorders by regulating Toll like receptor signaling pathways, tumor necrosis factor (TNF) signaling pathways, cancer pathways, and other pathways.Conclusions:The Shenqi Schisandra may exert anti anxiety effects by regulating related targets such as AKT1 and IL-6, regulating inflammatory reactions, cell apoptosis, and other processes.

Objective    To evaluate the feasibility and clinical value of robot-assisted lobectomy through anterior approach. Methods    We retrospectively analyzed the clinical data of 180 patients who underwent robot-assisted lobectomy through anterior approach in our hospital between April 2017 and February 2018. There were 97 males and 83 females, aged 59.5 (32.0-83.0) years. The clinical effects were analyzed. Results    One patient was transferred to thoracotomy due to tumor invasion of adjacent blood vessels and injury to the blood vessels, and there was no perioperative death. There were 8.5 (1.0-35.0) dissected lymph nodes for each patient. The median operation time was 120 (50-360) min, including robot Docking time 5 (1-23) min and robot operation time 65 (7-270) min. The median blood loss was 50 (5-1 500) mL, 132 (73.3%) patients had malignant tumors and median drainage time was 5 (2-30) d. The mean postoperative pain score was 3.4±0.7 points and the postoperative hospital time was 8 (2-32) d. At the median follow-up of 24 months, 11 patients developed recurrence and metastasis, and 3 died. Conclusion    Robot-assisted lobectomy through anterior approach is a safe and convenient operation method, which is worthy of clinical application.

Objective    To explore the clinical value of three-dimensional computed tomography bronchography and angiography (3D-CTBA) in robotic lung segmentectomy. Methods    A non-randomized control study was performed and continuously enrolled 122 patients who underwent robotic lung segmentectomy in our hospital from January 2019 to January 2020. 3D-CTBA was performed before operations in 53 patients [a 3D-CTBA group, including 18 males, 35 females, with a median age of 52 (26-69) years] and not performed in the other 69 patients [a traditional group, including 23 males, 46 females, with a median age of 48 (30-76) years]. The clinical data of the patients were compared between the two groups. Results    All the patients were successfully completed the surgery and recovered from hospital, with no perioperative death. The baseline characteristics of the patients were not significantly different between the two groups (P>0.05). No significant difference was found in the operative time [120 (70-185) min vs. 120 (45-225) min, P=0.801], blood loss [50 (20-300) mL vs. 30 (20-400) mL, P=0.778], complications rate (17.0% vs. 11.6%, P=0.162), postoperative hospital stay [7 (4-19) d vs. 7 (3-20) d, P=0.388] between the two groups. In the 3D-CTBA group, 5 (9.4%) patients did not find nodules after segmentectomy, and only 1 (1.9%) of them needed lobectomy, but in the traditional group, 8 (11.6%) patients did not find nodules and had to carry out lobectomy, the difference was statistically significant (P<0.05). The follow-up time was 10 (1-26) months, and during this period, there was no recurrence, metastasis or death in the two groups. Conclusion    3D-CTBA is helpful for accurate localization of nodules and reasonable surgical planning before operations, and reducing wrong resections in segmentectomy, without increasing the operation time, blood loss and complications. It is safe and effective in anatomical lung segmentectomy.

Objective: To observe whether an Xingnaojing 醒脑静 injection could improve the prognosis of patients, by increasing rifampicin penetration through the blood-brain barrier. Methods: Patients with severe tuberculous meningitis were enrolled in this study. The concentrations of Xingnaojing in cerebrospinal fluid and blood in patients treated with Xingnaojing and control were determined by high performance liquid chromatography. The changes in cerebrospinal fluid and the improvement of clinical symptoms and signs, were evaluated two weeks after admission. The long-term prognosis of the patients in the two groups were evaluated by the Glasgow Outcome Scale (GOS). Results: The concentration of rifampicin in cerebrospinal fluid was significantly higher in the Xingnaojing group (1.77±0.17 μg/mL), than in the control group (1.27±0.16 μg/mL, p<0.05). The difference in concentration of rifampicin in the blood was not significant (P>0.05). The short-term effective rate of the Xingnaojing group was 92.5% (37/40), which was significantly higher than that of the control group (80%, 32/40, p<0.05). After 6 months, 75% (30/40) of the Xingnaojing group had good prognosis according to the GOS score, whereas that of the control group was 50% (20/40) showing significantly better long-term treatment effect of the Xingnaojing group compared to the control group (P<0.05). Conclusion: Xingnaojing injection improved rifampicin penetration into the central nervous system. The increase in rifampicin concentration in cerebrospinal fluid improved outcomes in patients with severe tuberculous meningitis.

【Objective】To explore the effects of liver dysfunction in the third trimester of pregnancy on maternal outcomes and identify the factors affecting the maternal prognosis.【Methods】We collected the clinical data of 1 113 women with liver dysfunction in the third trimester of pregnancy （case group） and 1 113 normal pregnancies （control group） from the Third Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018. We compared the rates of cesarean section，premature delivery，placental abruption，postpartum hemorrhage and maternal mortality in the two groups，conducted the univariate and multivariate analysis for the case group and determined the prognostic risk factors by using Logistic regression. Receiver operating characteristic（ROC）curve analysis was applied to estimate the value of each independent risk factor for predicting liver dysfunction-related maternal mortality. 【Results】The rates of cesarean section，premature delivery，placental abruption，postpartum hemorrhage in the case group were higher than those in the control group（P < 0.05），and the odds ratios（ORs）were 3.59 ，7.81 ，10.68 and 2.93 ，respectively. The maternal mortality in the case group（1.2%）was higher than that in the control group（0.0%）（P < 0.05）. Logistic analysis revealed that high total bilirubin（TBIL），low prothrombin activity（PTA）and low fasting plasma glucose（FPG）were independent risk factors for liver dysfunction- related maternal mortality. The ROC curve analysis indicated that when TBIL was 235.4 μmol/L，the Youden′ s index in maximum was 0.331 with sensitivity of 0.818 and specificity of 0.513. When PTA was 20.5% ，the Youden′ s index in maximum was 0.366 with sensitivity of 0.821 and specificity of 0.545. When FPG was 3.11 mmol/L，the Youden′s index in maximum was 0.405 with sensitivity of 0.769 and specificity of 0.636.【Conclusion】Liver dysfunction in the third trimester of pregnancy has adverse effects on maternal outcomes. TBIL ，PTA and FPG are the factors affecting the maternal prognosis and may have certain predictive value for maternal death.

Objective:To summarize the experience of robotic and thoracoscopic segmentectomy in Daping Hospital, Army Medical University, and comparison analysis the clinical application value for early-stage lung cancer.Methods:A retrospective cohort study was conducted to continuously enroll 190 patients, 100 who received robotic(33 males and 67 females, median age of 51 years)and 90 who received VATS(34 males and 56 females, median age of 54 years), who underwent segmentectomy between June 2018 and October 2019. Perioperative outcomes(the operation time, intraoperative blood loss, postoperative thoracic drainage volume and time, pain score, complications, postoperative hospital stay and survival and mortality) were compared.Results:All the patients successfully completed the surgery and recovered from hospital, with no perioperative death.The baseline characteristics(sex, age, clinical symptoms, smoking status, underlying disease, tumor size, pathological type) and type of segmentectomy were comparable. There was significant difference in operative time[120(interquartile range, IQR 60-225)min vs. 155( IQR 75-330)min, P<0.001], blood loss[30( IQR 20-400) ml vs. 100( IQR 20-1 600) ml, P<0.001] between the robotic and VATS groups, respectively. But there was no significant difference in postoperative thoracic drainagevolume[4( IQR 1-15) days vs. 4( IQR 2-29) days, P=0.547], postoperative thoracic time[755( IQR 200-3 980)ml vs. 815( IQR 280-3 920)ml, P=0.902], pain score[2.33( IQR 0.88-4.75) points vs. 3.13( IQR 0.95-5.29)points, P=0.199], complications[7.4%(14/190) vs. 6.3%(12/190), P=0.303], postoperative hospital stay[7( IQR 3-19) days vs. 6( IQR 4-21) days, P=0.405] , number of lymph nodes[(4.83±3.18) vs.(6.15±4.1), P=0.255] between the robotic and VATS groups, respectively. The follow-up time was 6.5( IQR 1-26) months in the two groups, without recurrence, metastasis or death. Conclusion:Robotic lung segmentectomy is safe and feasible. This approach might lead to a better in operative time and blood loss. The short-term efficacy is similar with thoracoscopy, and the long-term efficacy needs further follow-up time.

Objective    To evaluate the feasibility and clinical value of robot-assisted lung segmentectomy through anterior approach. Methods    We retrospectively analyzed the clinical data of 77 patients who underwent robotic lung segmentectomy through anterior approach in our hospital between June 2018 to October 2019. There were 22 males and 55 females, aged 53 (30-71) years. Patients' symptoms, general conditions, preoperative imaging data, distribution of resected lung segments, operation time, bleeding volume, number of lymph node dissected, postoperative duration of chest tube insertion, drainage volume, postoperative hospital stay, postoperative complications, perioperative death and other indicators were analyzed. Results    All operations were successfully completed. There was no conversion to thoracotomy, serious complications or perioperative death. The postoperative pathology revealed early lung cancer in 48 patients, and benign tumors in 29 patients. The mean clinical parameters were following: the robot Docking time 1-30 (M=4) min, the operation time 30-170 (M=76) min, the blood loss 20-400 (M=30) mL, the drainage tube time 2-15 (M=4) days, the drainage fluid volume 200-3 980 (M=780) mL and the postoperative hospital time 3-19 (M=7) days. Conclusion    Robotic lung segmentectomy through anterior approach is a safe and convenient operation method for pulmonary nodules.

Objective: To propose the concept of a novel regional control and prevention (RCP) system for the outbreak of COVID-19 infectious disease, design an emergency epidemic prevention information system based on the existing network architecture and information system in the region, and a remote intelligent medical consultation and remote office platform, research and develop the technology of risk assessment and early warning for people in the region, and improve the regions’prevention and control ability facing emergency of major infectious diseases. Methods: Taking colleges, affiliated (teaching) hospitals, and cloud applications as typical RCP regional units, the existing local area network interaction methods between the cloud and universities and affiliated (teaching) hospitals are established to realize remote work in the network environment, remote medical imaging, psychological and ethical consultation and interaction; applying multi-agent propagation model based on complex network, combining Global Positioning System (GPS), Radio Frequency Identification (RFID), and electronic fence technology, to realize the risk classification and early warning of units and personnel in the area. Results: In the RCP, a system architecture combining campus network, affiliated (teaching) hospital intranet, and the Internet is used. Dynamic connection is made using distributed technology and cloud storage. The data buffer mechanism of the intermediary database in the network realized telemedicine consultation and telecommuting. Relying on the platform, multi-agent propagation model based on complex network and cellular automaton model are used to realize the score and early warning of population exposure risk in the region by using GPS, RFID and electronic fence technology. Conclusions In the epidemic phase of major infectious diseases, the construction of RCP can improve the response speed of wartime epidemic prevention, provide reasonable data-based warnings and risk ratings, and reduce the exposure risk of susceptible people. The design and development of RCP is a systematic project that needs to combine regional structural and functional characteristics, and the foundation of the early informatization work in the region and the level of the emergency development team determine the development progress, maintenance, and actual application effects. It is recommended to establish a peacetime and wartime combined RCP mode and incorporate it into the government's disease control system to improve the national and regional level of prevention and control of major infectious diseases.

Massive open online courses (MOOC) is an emerging teaching mode based on website, which has been developed rapidly in China since 2013. Contemporary medical education, assisted by MOOC, diverges greatly with various modes. In this paper, the current situation and advantages of MOOC on medical education in the information age were analyzed, and suggestions for improvement of MOOC on modern medical education were proposed in combination with foreign case study, which is conducive to the reform and innovation of medical education model.