OBJECTIVE To investigate the metabolic changes in MEG-01 megakaryocytes after treatment with linezolid （LZD） from metabolomic perspective and its impact on the the proliferation of cells and generation of platelet precursors. METHODS MEG-01 cells were seeded in proliferation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 100， 200， 400， 800 μg/mL LZD groups. The proliferation status of cells in each group was observed under the microscope； cell proliferation and viability were assessed. Cells were also seeded in differentiation medium and divided into blank control group （untreated）， solvent control group （4‰DMSO）， and 400 μg/mL LZD group； after 14 days of culture， platelet precursor generation was observed under the microscope； immunofluorescence staining was performed to count the proportion of cells producing pseudopodia， the relative length of pseudopodia was measured， and the expression levels of CD41 and CD42b mRNA were assessed. Cells from the solvent control group and the 400 μg/mL LZD group， cultured in differentiation medium for 14 days， were extracted and subjected to non-targeted metabolomics and targeted energy metabolomics analysis using liquid chromatography-tandem mass spectrometry. The relative content of pyruvate in cells， after being cultured for 14 days with the addition of pyruvate （10 mmol/L） or LZD （400 μg/mL）+pyruvate （10 mmol/L）， was measured and observed， as well as its effects on cell proliferation and platelet precursor generation. RESULTS 400 μg/mL LZD could significantly inhibit the proliferation of MEG-01 cells and the generation of platelet precursors （P＜0.01）. Non-targeted metabolomic analysis of MEG-01 cells after 400 μg/mL LZD treatment revealed significant changes in energy metabolism-related pathways such as mTOR signaling pathway， alanine， aspartate and glutamate metabolism， and central carbon metabolism in cancer. Targeted energy metabolomic analysis further showed that the relative contents of adenosine triphosphate， guanosine triphosphate， and pyruvate in MEG-01 cells were significantly reduced （P＜0.01）， while the relative contents of lactate were significantly increased （P＜0.01）. Compared with the LZD group， the relative content of pyruvate， cell count， the proportion of cells producing pseudopodia and the relative length of pseudopodia were significantly increased in the LZD+pyruvate group （P＜0.01）. CONCLUSIONS LZD may reduce pyruvate production by inhibiting mitochondrial energy metabolism， thereby suppressing megakaryocyte proliferation and platelet precursor production， ultimately leading to the occurrence of thrombocytopenia.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

With the advantage of high efficiency， low toxicity and targeting， liposomes have become the research hotspot of new drug preparations at home and abroad. In this paper， the research progress in recent years is reviewed from the aspects of preparation methods， classification and clinical application of liposomes. The results showed that in order to obtain more stable and controllable liposomes， scholars improved and optimized the traditional preparation methods and established novel preparation methods such as supercritical fluid methods， freeze-drying method and double-asymmetric centrifugation method. In order to enhance the efficacy and reduce toxicity， the conventional liposomes were optimized to get novel ones such as environmentally sensitive liposomes， long-circulating liposomes and multifunctional liposomes， which had greatly promoted the clinical application of liposomes. For now， liposomes have been used in many fields， such as anti-cancer agents， antimicrobial and vaccines， but most of the new liposomes are still in the early stage of development.

OBJECTIVE：To explo re the clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia before ADR. METHODS ：The medical records of 411 patients receiving voriconazole therapy ， who admitted to our hospital from January 2018 to November 2020，were retrospectively analyzed. The general information of all patients，including sex ，age，body weight ，type of infection ，underlying disease ，type of pathogenic fungal infection and administration route of voriconazole ，maintenance dose ，blood drug concentration ，were collected. The basic information of patients with neurological ADR ，including sex ，age，types of infection ，underlying disease ，drug combination ，occurrence time and clinical manifestations ，were collected . The levels of blood potassium ，blood sodium and liver function indexes （ALT，AST， γ-GT，ALP，total bilirubin ，direct bilirubin ）within 3 days before the neurological ADR were also collected. The relationship of neurological ADR with voriconazole trough concentration ，blood potassium and blood sodium levels was analyzed. RESULTS ： Among 411 patients，31（7.54％）patients suffered from neurological ADR ，which were higher in male （64.52％）than in female （35.48％），mainly in patients aged 50 and over （74.20％）. The major infection type was lung infection （96.77％）. Among 31 patients with neurological ADR ，26 patients suffered from neurological ADR after 1-7 days after voriconazole administration ， accounting for 83.87％. Thirty patients received intravenous drip ，accounting for 96.77％. The incidence of neurological ADR in patients with voriconazole trough concentration ＞5.0 μ g/mL （8.99％）was significantly higher than that in patients with trough concentration ≤5.0 μg/mL（3.42％，χ2＝4.91，P＝0.027）. The clinical manifestations of the patients were mainly 023-68766797。E-mail：cheng7zhu@163.com hallucinations（32.35％），irritability（32.35％）and poor sleep （17.65％），etc. Within 3 days before 30 patients，receiving related indexes test ，suffered from neurological ADR ，16 patients（53.33％）had hypokalemia and 12 patients（40.00％） had hyponatremia ，which w ere significantly higher than the incidence of hypokalemia （24.74％，P＝0.001）and hyponatremia （12.89％，P＜0.001）in those without neurological ADR . There were 8，10，7，13，7 and 10 patients with ALT ，AST，ALP， γ-GT，total bilirubin and direct bilirubin increased. In 31 patients with neurological ADR ，the neurological ADR were relieved or disappeared after reducing the dosage or discontinuing voriconazole. CONCLUSIONS ：The neurological ADR of voriconazole mostly occurs 1-7 days after voriconazole administration ，mainly by intravenous drip ，mostly in male and people aged 50 and over. The occurrence of neurological ADR may be related to trough concentration of voriconazole ，and most patients suffer from hypokalemia or hyponatremia before the occurrence of ADR .

OBJECTIVE：To systematically evaluate th e efficacy and safety of glucagon-like peptide 1 receptor agonists semaglutide in the treatment of type 2 diabetes mellitus （T2DM），and to provide evidence-based reference for clinical treatment of T2DM. METHODS ：Retrieved from PubMed ，Embase，the Cochrane library ，ClinicalTrials.gov，CBM，CNKI and VIP ， randomized controlled trials （RCT） about oral semaglutide 3 mg，7 mg and 14 mg （trial group ） versus placebo or other glucose-lowering drugs （control group ）in the treatment of T 2DM were selected during the inception to May 2020. After extracting data from clinical studies that met the inclusion criteria ，quality evaluation was carried out with Cochrane systematic evaluation manual 5.1.0，Meta-analysis was performed by using Rev Man 5.3 statistical software. RESULTS ：A total of 6 RCTs involving 5 334 patients were included. Results of Meta-analysis showed that compared with control group ，trial group could significantly decreased HbA 1c level { 26 weeks [MD＝－0.62，95％CI（－0.88，－0.36），P＜0.001]，52 weeks [MD＝－0.51，95％CI（－0.72， －0.29），P＜0.001]}，FPG level { 26 weeks [MD＝－0.89，95％ CI（－1.31，－0.48），P＜0.001]，52 weeks [MD＝－0.68，95％CI （－1.05，－0.31），P＜0.001]}；significantly increased the compliance rate of HbA 1c＜7％ {26 weeks [RR＝2.22，95％CI（1.68， 2.93），P＜0.001]，52 weeks [RR＝2.02，95％CI（1.51，2.70），P＜0.001]}；significantly decreased the self-measured plasma glucose ， body weight and diastolic blood pressure （DBP）after 26 and 52 weeks of treatment，self-measured postprandial glucose cstc2015zdcy-ztzx120005） after 26 weeks of treatment and systolic blood pressure （SBP） E-mail： after 52 weeks of treatment（P＜0.05）. Subgroup analysis of different doses showed that compared with control group ，3 mg subgroup could significantly decreased the body weight after 26 and 52 weeks of treatment and DBP a fter 52 weeks of treatment ；7 mg subgroup could significantly decreased the HbA 1c levels and body weight after 26 and 52 weeks of treatment ，the FPG levels and the self-measured plasma glucose after 26 weeks of treatment and the SBP after 52 weeks of treatment ，increased the compliance rate of HbA 1c＜7％ after 26 weeks of treatment. The 14 mg subgroup could significantly decreased the HbA 1c levels ，the FPG levels ，the self-measured plasma glucose levels ，the body weight and the SBP after 26 and 52 weeks of treatment ，and self-measured postprandial glucose after 26 weeks of treatment ，while increased the complication rate of HbA 1c＜7％ after 26 and 52 weeks of treatment （P＜0.05）. The incidence of hypoglycemia events in trial group [RR ＝0.84，95％CI（0.72，0.97），P＝0.02] was significantly lower than control group ，but the incidence of adverse events [RR ＝1.23，95％CI（1.09，1.40），P＝0.001] and gastrointestinal reaction [RR ＝1.99，95％CI（1.55，2.57），P＜0.001] were significantly higher than control group. There was no significant difference in the incidence of serious adverse events or infection between 2 groups（P＞0.05）. CONCLUSIONS ：Oral semaglutide can effectively decrease blood glucose level ，increase the compliance rate of HbA 1c＜7.0％，reduce the body weight and blood pressure level of T 2DM patients ，and the 14 mg subgroup has the best effect. When using somaluptide ， we should pay attention to the occurrence of adverse events ， especially gastrointestinal adverse events.

Objective: To investigate the application effect of metoprolol in the treatment of atrial fibrillation complicated with chronic heart failure(CHF). Methods: From February 2015 to February 2019, 398 elderly patients with atrial fibrillation and CHF in Wangjiangshan Branch of the People's Hospital of Zhejiang Province were selected in the study.The patients were divided into two groups according to the digital table, with 199 case in each group.The control group was treated with rest, digitalis inhalation, diuretics, angiotensin converting enzyme inhibitors, nitrate and enteric-coated aspirin.The observation group was treated with metoprolol on this basis.The effective rate of treatment, heart rate changes before and after treatment, left ventricular ejection fraction and 6-minute walking distance in the two groups were observed and analyzed. Results: The effective rate of the observation group was 88.94%(177/199), which was significantly higher than 71.86%(143/199) in the control group, the difference was statistically significant (χ²=18.433, P=0.000). The highest heart rate, the lowest heart rate and the resting heart rate in the observation group after treatment were significantly better than those in the control group[(115.12±0.35)times/min vs.(122.12±16.22)times/min, (90.21±18.12)times/min vs.(94.12±11.11)times/min, (97.00±9.64)times/min vs.(102.03±11.20)times/min], the differences were statistically significant(t=4.246, 4.783, 4.662, all P<0.05). The LVEF and 6-minute walking distance of the observation group after treatment were significantly better than those of the control group[(45.0±2.0)% vs.(41.0±3.0)%, (340.09±31.45)m vs.(302.43±29.45)m], the differences were statistically significant(t=4.246, 7.662, all P<0.05). Conclusion Digitalis combined with metoprolol can effectively control the heart rate of atrial fibrillation combined with CHF, improve ventricular function and increase cardiac endurance.The combined therapy is worthy of promoting in this disease.

OBJECTIVE： To systematically evaluate effectiveness of prophylactic application of carbapenems for severe acute pancreatitis （SAP）， and to provide evidence-based reference in clinic. METHODS： Retrieved from PubMed， Embase， Medline， Cochrane Library， CNKI and VIP database，randomized controlled trials （RCTs） about effectiveness of prophylactic application of carbapenems （trial group） versus placebo or non-prophylactic use of antibiotics （control group） for SAP were included， and the retrieval time was from establishment to Dec. 2018. After extracting data from clinical studies that met the inclusion criteria， methodological quality of included studies were evaluated by using Cochrane bias risk assessment tool 5.1.0 and modified Jadad scoring scale， and Meta-analysis was performed for pancreatic infection rate， extrapancreatic infection rate， surgical intervention rate and mortality rate by using Rev Man 5.3 statistical software. RESULTS： A total of 8 RCTs were included， involving 544 patients. Meta-analysis showed that there was no statistical significance in the pancreatic infection rate [RR＝0.84， 95％CI （0.58， 1.22）， P＝0.36]， extra-pancreatic infection rate [RR＝0.76， 95％CI （0.43， 1.35）， P＝0.35] and surgical intervention rate [RR＝0.93， 95％CI （0.65， 1.32）， P＝0.68] or mortality rate [RR＝0.99， 95％CI（0.59，1.65）， P＝0.97] between 2 groups. CONCLUSIONS： The prophylactic use of carbapenems can not reduce pancreatic or extra-pancreatic infection rate， surgical intervention rate and mortality rate.

Patients with liver disease are at an increased risk of both embolism and bleeding. The optimal anticoagulation strategy remains unclear when associated with venous thromboembolic disease. Moreover, currently approved oral anticoagulant drugs undergo metabolism and elimination in the liver with varying degrees of hepatic dysfunction. Thus, impaired liver function may lead to increased risk of bleeding, making anticoagulant therapy more intricate. This article summarizes the risk of bleeding and thrombosis in patients with liver disease, and the clinical research progress of oral anticoagulants in patients with liver disease to facilitate evidence for choosing oral anticoagulants therapy when required.

By referring to the management model of chief residents, the system of chief resident pharmacists is established to promote the training of clinical pharmacists and the construction of clinical pharmacy disciplines. Professional clinical pharmacists are elected to be the chief resident pharmacists, who are designated based on qualification for application, appointment procedures, scope of responsibilities and job description. The establishment and implementation of the chief resident pharmacist system plays a positive role on the team building of high-quality clinical pharmacists, accelerating the development of clinical pharmacy disciplines. It can serve as an important measure to further strengthening the construction of clinical pharmacists system.

Medication safety is a top concern for medical institutions. Outpatient prescription standard is designed to standardize prescription, dispensing, and supervision for outpatient and emergency prescriptions at medical institutions. The standard covered prescription authorization management, prescription issuance, prescription dispensing, prescription saving and supervision. These four parts focus on risk exposure of patients′medication safety, and aim at safeguarding patient medication safety, which were formulated according to China′s laws and regulations, domestic and international industrial standards and technical specifications, as well as prescription conditions at medical institutions and experts opinions. The standard covers technical requirements and guidance, management measures and system development, serving as an important basis to guide medical institutions on standardize management of outpatient prescription and emergency prescription.