Due to their potential application as novel antibiotics, antimicrobial peptides are attracting much attention. Large quantities of highly purified peptides are crucial to basic and clinical studies. Natural resources of antimicrobial peptides are limited and hard to purify, chemical synthesis is of high-cost and unstable, so recombinant expression of antimicrobial peptides is a cost-effective way. Escherichia coli has been the most widely used as host to express antimicrobial peptides with fusion protein, which can not only avoid the lethal effect towards the host, but also protect the peptide from degradation by proteases. Combined with our research, the present article reviews the progress of fusion vector, cleavage methods and optimization options for antimicrobial peptides production with fusion protein in Escherichia coli.
Antimicrobial Cationic Peptides ; biosynthesis ; Escherichia coli ; metabolism ; Genetic Vectors ; Recombinant Fusion Proteins ; biosynthesis

Objective To establish a citrate pharmacokinetics model which is applied to evaluate the risk of citrate accumulation in patients with liver dysfunction in the continuous renal replacement treatment (CRRT) with regional citrate anticoagulation (RCA). Methods The source of citrate for extracorporeal anticoagulation, the body clearance and filter elimination of citrate, which were the three major citrate fluxes of systemic citrate level, were combined into a single-pool, first order kinetic equation. The data from a published clinical study of systemic citrate kinetics in the intensive care unit patients with or without liver cirrhosis were adapted and the citrate kinetic equation was applied to predict the risk of systemic citrate accumulation in patients with normal, impaired and absent liver clearance while different RCA-CRRT protocols were carried out. Results The single pool, first order citrate kinetic modeling equation was as follows:Csys=C(0)·e-[(clb+clf)·t/V]+G/CLb+CLf×(1-e-[(clb+clf)·t/V])There was excellent agreement between published citrate measurements and our predictions. Kinetic modeling showed that the plasma citrate concentration of patients with normal citrate body clearance was no more than 1 mmol/L during common RCA-CRRT. The model predicted that when the single pass fractional extraction of citrate on the artificial kidney was above 66％, systemic steady citrate concentration would be among the safe range even in patients of impaired body metabolism of citrate.Conclusions The citrate kinetic model of RCA-CRRT can predict the risk of systemic citrate accumulation and provide the basis for designing the safe RCA-protocols for the patients with impaired body clearance of citrate.

Objective To study the protective effects ofcatalpol on cardiomyocytes in type 2 diabetic rats.Methods Based on the method of random number table,8-wee k-old SD rats were randomly divided into normal group (10 rats) and experimental group (90 rats).The rats in the experimental group that were fed with high-fat and high-sugar diet for 8 weeks were injected intraperitoneally with STZ (15 mg/kg),with fasting blood glucose≥16.7mmol/L as a model for type 2 diabetes.Then based on fasting blood glucose and body weight,the rats meeting the criteria of type 2 diabete mellitus were randomy divided into five group,namely,the model group,the control group,the low or medium and high doses of the catalpol group,and there were 12 rats in each group.The normal group and the model group were filled with distilled water (5 ml/kg·d,the control group were treated with metformin (90 mg/kg·d),and Low,medium and high dose group were intragastric administration of Catalpol(2.5,5,10 mg/kg·d).Then,the level of glucose,myocardial oxidative stress related protein,cardiac strcture and function change were measured after 12 weeks of intervention in rats.Results Compared with the model group,the level of fasting blood glucose in catalpol low,medium and high dose groups was significantly lower (P＜0.05).The levels of SOD (197.43 ± 8.85 U/ml,186.54 ± 5.89 U/ml,175.62 ± 7.67 U/ml vs.157.75 ±11.29 U/ml) in myocardial tissue of those groups significantly increased (P＜0.05),the levels of MDA (7.26 ±0.72 nmol/mg,8.58 ± 0.93 nmol/mg,10.62 ± 0.59 nmol/mg vs.14.80 ± 0.71 nmol/mg) in myocardial tissue of those groups significantly decreased (P＜0.05),the E/A value (1.25 ± 0.18,1.09 ± 0.14,0.97 ± 0.11 vs.0.51 ±0.11) in those groups significantly increased (P＜0.05),the E/E'values (12.33 ± 0.73,13.26 ± 1.07,14.73 ± 1.23 vs.20.54 ± 1.64) and the IVRT (21.90 ± 2.60 ms,22.05 ± 2.84 ms,24.42 ± 2.22 ms vs.27.40 ± 2.81 ms) in those groups significantly decreased (P＜0.05).Conclusions The catalpol can reduce oxidative stress,improve cardiac function and protect cardiomyocytes.

OBJECTIVE To provide reference for safe drug use in patients with anaplastic lymphoma kinase （ALK）-positive non-small cell lung cancer （NSCLC）. METHODS Clinical pharmacists participated in the diagnosis and treatment of a patient with ALK-positive NSCLC who developed bilateral pleural effusion and hemolytic anemia after taking alectinib； regarding symptoms such as pleural effusion and hemolytic anemia in the patient， clinical pharmacists investigated the patient’s history of medication and disease， as well as potential drug interaction； to consider the correlation between the patient’s use of alectinib and the duration of pleural effusion and hemolytic anemia， clinical pharmacists suggested that clinical doctors discontinued alectinib and used reduced dose treatment after the pleural effusion improved， but the patient suffered from bilateral pleural effusion and hemolytic anemia again； after evaluating the correlation between alectinib and bilateral pleural effusion and hemolytic anemia using the Naranjo’s assessment scale， clinical pharmacists recommend permanent discontinuation of alectinib and jointly recommend replacement with ensartinib with clinical physicians. RESULTS Physicians adopted the suggestions of clinical pharmacists. The pleural effusion subsequently regressed and hemolytic anemia improved after replacing the drug. The correlation between alectinib and bilateral pleural effusion and hemolytic anemia was confirmed. CONCLUSIONS Clinical pharmacists participate in pharmaceutical monitoring of ALK-positive NSCLC patients， assist clinical doctors in developing personalized medication recommendations， and ensure the safety of patient medication.

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir-ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.
Humans ; Ritonavir/therapeutic use* ; COVID-19 ; Antiviral Agents/therapeutic use* ; China ; Nitriles ; Lactams ; Proline ; Adenosine/analogs & derivatives* ; Leucine

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*