Immunogenic Cell Death ; Prognosis ; Immunotherapy ; Neoplasms

Objective:To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.Methods:The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results:A total of 1 486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant (all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM [before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752); after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05]. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy. Conclusion:The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

Objective:To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. (the generic drug) and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co., Ltd. (the original drug) in antiplatelet therapy.Methods:The study design was a retrospective cohort study. The subjects were patients who underwent percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021. Through the hospital electronic medical record system, relevant clinical data of patients (age, gender, comorbidities, blood lipid level on admission, PCI indications, antiplatelet treatment regimen, efficacy and safety assessment endpoint events within 12 months of treatment, etc.) were collected. The patients were divided into the generic drug group and the original drug group. To exclude confounders, propensity score matching (PSM) method was used. The efficacy evaluation index was the incidence of the primary endpoint events (cardiogenic death, stroke, target revascularization, recurrent infarction) and secondary endpoint events (all-cause mortality, peripheral artery occlusion, stent thrombosis, angina attacks) within 12 months of treatment. The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results:A total of 1 486 patients were included in this study, including 734 in the generic drug group and 752 in the original drug group. The proportion of women and unstable angina, and the level of high-density lipoprotein cholesterol were higher than those in the original drug group (all P<0.05). The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group (both P<0.05). After PSM, 690 patients were enrolled in the generic drug group and 690 patients in the original drug group (all P>0.05). No differences in the comparison of clinical features between the 2 groups was significant (all P>0.05). No differences in the incidences of primary endpoints, secondary endpoints, and bleeding events between the 2 groups was significant before and after PSM [before PSM: 12.1%(89/734) vs. 10.9%(82/752), 10.8%(79/734) vs. 8.4%(63/752), 0.3%(2/734) vs. 0.5%(4/752); after PSM: 12.6%(87/690) vs. 12.3%(85/690), 11.0%(76/690) vs. 8.3%(57/690), 0.3%(2/690) vs. 0.4%(3/690); all P>0.05]. No death occurred in patients of both groups. Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae, which did not lead to interruption of antiplatelet therapy. Conclusion:The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co., Ltd. for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.

Objective:To systematically evaluate the occurrence of interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).Methods:PubMed, Embase, The Cochrane Library, CNKI, WanFang, and VIP databases were searched up to April 30, 2022. Randomized controlled trials (RCT) about NSCLC treated with EGFR-TKI (8 kinds listed in China, including gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, almonertinib, and furmonertinib) compared with chemotherapy were collected. Patients was treated with EGFR-TKI monotherapy in the trial group and chemotherapy in the control group. The outcomes included the occurrence of ILD. RevMan 5.4 software was used for meta-analysis, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Results:A total of 15 RCT were entered in the analysis, including 6 about gefitinib, 5 about erlotinib, 2 about icotinib, and 2 about afatinib, involving 2 318 patients in the trial group and 1 975 in the control group. Meta-analysis showed that the overall incidence of ILD in the trial group were higher than that in the control group [1.47% (34/2 318) vs. 0.51% (10/1 975), OR=2.44, P=0.004]; difference in incidences of ILD-related death between the 2 groups was not significant [0.35% (8/2 318) vs. 0.05% (1/1 975), OR=3.29, P=0.07]. The severity of ILD was graded in 14 RCT, and the meta-analysis showed that the incidence of more than grade 3 ILD in the trial group was higher than that in the control group [0.62%(13/2 089) vs. 0.11% (2/1 864), OR=2.60, P=0.04]. The overall incidences of ILD and the incidences of more than grade 3 ILD in the gefitinib group were higher than those in the corresponding control groups [2.31%(27/1 167) vs. 0.71% (8/1 123), OR=2.88, P=0.004; 0.86% (7/1 167) vs. 0.09% (1/1 123), OR=3.98, P=0.03]. There was no significant difference in ILD occurrence between the trial group and the control group for afatinib and erlotinib (all P>0.05). No ILD occurred in the trail group or in the control group in RCT about icotinib. Conclusions:Compared with chemotherapy, NSCLC patients receiving EGFR-TKI, especially gefitinib, have higher risks of ILD and serious ILD. Therefore, clinical vigilance and monitoring should be strengthened.

Objective:To systematically evaluate the occurrence of interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).Methods:PubMed, Embase, The Cochrane Library, CNKI, WanFang, and VIP databases were searched up to April 30, 2022. Randomized controlled trials (RCT) about NSCLC treated with EGFR-TKI (8 kinds listed in China, including gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, almonertinib, and furmonertinib) compared with chemotherapy were collected. Patients was treated with EGFR-TKI monotherapy in the trial group and chemotherapy in the control group. The outcomes included the occurrence of ILD. RevMan 5.4 software was used for meta-analysis, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Results:A total of 15 RCT were entered in the analysis, including 6 about gefitinib, 5 about erlotinib, 2 about icotinib, and 2 about afatinib, involving 2 318 patients in the trial group and 1 975 in the control group. Meta-analysis showed that the overall incidence of ILD in the trial group were higher than that in the control group [1.47% (34/2 318) vs. 0.51% (10/1 975), OR=2.44, P=0.004]; difference in incidences of ILD-related death between the 2 groups was not significant [0.35% (8/2 318) vs. 0.05% (1/1 975), OR=3.29, P=0.07]. The severity of ILD was graded in 14 RCT, and the meta-analysis showed that the incidence of more than grade 3 ILD in the trial group was higher than that in the control group [0.62%(13/2 089) vs. 0.11% (2/1 864), OR=2.60, P=0.04]. The overall incidences of ILD and the incidences of more than grade 3 ILD in the gefitinib group were higher than those in the corresponding control groups [2.31%(27/1 167) vs. 0.71% (8/1 123), OR=2.88, P=0.004; 0.86% (7/1 167) vs. 0.09% (1/1 123), OR=3.98, P=0.03]. There was no significant difference in ILD occurrence between the trial group and the control group for afatinib and erlotinib (all P>0.05). No ILD occurred in the trail group or in the control group in RCT about icotinib. Conclusions:Compared with chemotherapy, NSCLC patients receiving EGFR-TKI, especially gefitinib, have higher risks of ILD and serious ILD. Therefore, clinical vigilance and monitoring should be strengthened.

OBJECTIVE：To provid e reference for pharmaceutical workers to better understand Novel Coronavirus Infection ： Expert Consensus on Guidance and Prevention Strategies for Hospital Pharmacists and the Pharmacy Workforce （hereinafter referred to as “expert consensus ”），and to apply and practice in specific work ，so as to give full play to the role of pharmacists to help fight the epidemic.METHODS ：The background of the formulation and revision of the expert consensus were introduced ，and its main contents and viewpoints were interpreted. RESULTS & CONCLUSIONS ：The text of expert consensus is divided into 8 parts，mainly including disease diagnosis and treatment [SARS-CoV- 2 infection related background ，clinical manifestations and diagnosis， treatment]，hospital pharmacy （prevention and control strategy ，work guidance ），drug and facility support management（key drug/facility/equipment support ，management and use of the drug in special circumstances ），information sources and related resources ，etc.，which comprehensively and detailedly provide information ，guidance and strategies for coronavirus SARS-CoV-2 infection prevention and control to play the role of pharmacists in hospital pharmacy well ，do well in the protection of staff in different pharmaceutical posts ，drug security work in response to epidemic situation ，and develop pharmaceutical care. So far，the understanding of SARS-CoV- 2 in the pharmaceutical industry is relatively limited. Based on the accumulated experience and progress in epidemic prevention and control ，the expert consensus will be updated and improved continuously ，so as to provide guidance and help for hospital pharmaceutical personnel.

OBJECTIVE：To provide drug ，material supp ly and emergency management reference for novel coronavirus （SARS-CoV-2）infection in pharmacy staff in hospital. METHODS ：The method of 5M1E was used to analyze the six main factors，including man ，machine，material，method，environment and measurement of drug ，material supply and emergency management. The relevant prevention and control strategies were put forward. RESULTS & CONCLUSIONS ：In the drug ，material supply and emergency management of epidemic prevention and control ，the man factors were involved ，such as mainly pharmacists from pharmacy departments of medical institutions. At the same time ，the management also involved machine factors such as drug storage，cleaning and disinfection ；material factors such as emergency drugs ，disinfection products ，in vitro diagnostic reagents ， the guarantee of medicine materials for medical team ，investigational products ；methods factors such as relevant management measures；environmental factors such as storage environment and facilities ；measurement factors such as drug use ，drug and substance reserve. In view of the above factors ，it is suggested to strengthen the professional knowledge and communication skills training of pharmacists ，and strengthen humanistic care ，so as to improve their post competency ，communication in emergency response and psychological tolerance. Equipment and materials management shall be strengthened ，and equipment maintenance and disinfection shall be done well to ensure normal use of equipment. According to the evidence-based method ，the emergency drug list should be established. According to the disinfection protection requirements ，the disinfection products should be reasonably selected and their quality and sufficient inventory should be ensured. The qualified in vitro diagnostic reagents should be purchased in time. The investigational products should be managed reasonably according to the relevant requirements of clinical trials ，to ensure the drug and material supply of medical team members. Emergency plans and standard operating procedures shall be formulated，the principle of sympathetic drug use shall be followed ，and the management of off-label drug use and early warning of drug and material shortage shall be done well. Reasonable storage space should be reserved to strengthen environmental monitoring and disinfection. We should strengthen the monitoring and reporting of daily data ，strengthen the quality monitoring ， and accept the independent audit of the third party. Above strategies are helpful to improve the ability of drug supply risk identification and response ability ，and cooperate with the medical team to timely rescue patients.

Objective To evaluate the effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Eighty NYHA class Ⅱ or Ⅲ patients of both sexes,aged 21-59,scheduled for cardiac valve replacement with CPB,were randomly divided into 4 groups ( n =20 each):normal saline control group ( group C ),ulinastatin preconditioning group ( group U1 ),ulinastatin postconditioning group (group U2 ) and ulinastatin preconditioning plus postconditioning group(group U3 ).In group U1,uinastatin 20 000U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 from after tracheal intubation until 10 min before ascending aortic cross-clamping.In group U2,ulinastatin 10 000 U/kg was perfused via aortic root at 4000-5000 U· kg-1 · min-1 at 5-7 min before aortic unclamping.In group U3,ulinastatin preconditioning and postconditioning were performed as described in groups U1 and U2.In group C same volume normal saline was infused instead of ulinastatin.Blood samples were taken from radial artery at 10 min before ascending aortic cross-clamping,40 min after ascending aortic cross-clamping,45 min after aortic unclamping and the end of operation for determination of plasma concentrations of TNF-α and soluble tumor necrosis factor receptor 1 (sTNF-R1).Myocardial tissues were obtained from right atrial appendage at 45 min after aortic unclamping for determination the expression of TNF-d,Bcl-2,Bax and caspase-3 and apoptosis.The Bcl-2/Bax ratio and apoptotic index were calculated.Results Plasma concentrations of TNF-α and sTNF-R1 and the expression of TNF-α,Bax,caspase-3 and apoptotic index were lower,the expression of Bcl-2 and Bcl-2/Bax ratio were higher in groups U1,U2 and U3 thah group C and in group U3 than groups U1,U2 ( P ＜ 0.05 ).Conclusion Ulinastatin postconditioning can inhibit myocardial apoptosis in patients undergoing cardiac valve replacement with CPB,and efficacy of combination of ulinastatin preconditioning and postconditioning is stronger than that of ulinastatin postconditioning.The mechanism is involved in balancing the expression of Bax and Bcl-2 and down-regulating the expression of TNF-α and its receptor.