Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

Evaluation of the efficacy of endoscopic posterior nasal neurectomy with pharyngeal neurectomy of allergic rhinitis combined with chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the effect of posterior nasal neurectomy（PNN） with pharyngeal neurectomy （PN） on chronic sinusitis with nasal polyps （CRSwNP）complicated with perennial allergic rhinitis （PAR）. Methods:83 patients with perennial allergic rhinitis combined with chronic group-wide sinusitis with nasal polyps who attended our hospital from July 2020 to July 2021 were selected. All patients underwent conventional functional endoscopic sinusitis surgery（FESS）+ nasal polypectomy. Patients were divided according to whether they underwent PNN+PN. 38 cases in the experimental group underwent FESS combined with PNN+PN; 44 cases in the control group underwent conventional FESS alone. All patients underwent the VAS, RQLQ, and MLK before treatment, and at 6 months and 1 year after surgery. Meanwhile, other relevant data were collected and the preoperative and postoperative follow-up data were collected and analyzed to assess the differences between the two groups. Results:The total postoperative follow-up period was 1 year. The recurrence rate of nasal polyps at 1 year postoperatively and the nasal congestion VAS score at 6 months postoperatively were not statistically significant in the two groups（P>0.05）. However, the patients in the experimental group had statistically significantly lower effusion and sneezing VAS scores, MLK endoscopy scores and RQLQ scores at 6 months and 1 year postoperatively, and nasal congestion VAS scores at 1 year postoperatively compared to the control group（P<0.05）. Conclusion:For patients with perennial AR complicated with CRSwNP, the combination of the PNN+PN in FESS can significantly improve the short-term curative effect, and PNN+PN is a safe and effective surgical treatment.

Mediation of serum albumin in the association of serum potassium with mortality in Chinese dialysis patients: a prospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration.@*METHODS@#This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities.@*RESULTS@#A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ± 14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation.@*CONCLUSIONS@#Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

The mechanisms of Glycyrrhizae Radix et Rhizoma and its honey-processed products on improving cisplatin-induced acute kidney injury in rats based on metabolomics / 药学学报

This study used metabolomics to explore the improvement effect of raw and honey-processed Glycyrrhizae Radix et Rhizoma on acute kidney injury (AKI) in rats. All animal experiments were approved by the Animal Ethics Committee of Shandong Academy of Chinese Medicine (approval No.: SDZYY20200101001). SD rats were randomly divided into normal group, model group, raw Glycyrrhizae Radix et Rhizoma group (0.9 g·kg-1) and honey-processed Glycyrrhizae Radix et Rhizoma group (0.9 g·kg-1), 6 rats in each group. The rats model of acute kidney injury was established by single intraperitoneal injection of cisplatin (CP) and treated with raw and honey-processed Glycyrrhizae Radix et Rhizoma. The pathological changes of renal tissue were evaluated by hematoxylin and eosin (HE) and PAS staining, the contents creatinine (Cr), blood urea nitrogen (BUN) and superoxide dismutase (SOD) in serum were detected. UPLC-Q-TOF/MS was used to study tissue metabolomics to screen the biomarkers affected by raw and honey-processed Glycyrrhizae Radix et Rhizoma and analyz the metabolic pathways. The results showed that compared with the model group, raw and honey-processed Glycyrrhizae Radix et Rhizoma can significantly improve the pathological changes of renal tissue and decrease the content of Cr, BUN and increase the activity of SOD. In addition, honey-processed Glycyrrhizae Radix et Rhizoma can also significantly reduce the kidney index. In tissue samples, 45 biomarkers were measured in AKI rats. Raw Glycyrrhizae Radix et Rhizoma and honey-processed Glycyrrhizae Radix et Rhizoma could simultaneously call back 11 differential metabolites, which were involved in the regulation of glycerophospholipid metabolism, tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glutathione metabolism. In addition, raw Glycyrrhizae Radix et Rhizoma is also involved in the regulation of glycine, serine and threonine metabolism and pyrimidine metabolism. In summary, raw and honey-processed Glycyrrhizae Radix et Rhizoma can participate in the regulation of different metabolic pathways, and play an improvement role in AKI rats by regulating amino acid, lipid metabolism, energy metabolism and oxidative stress.

Ethical Dilemma of "Virus Sovereignty" / 中国医学伦理学

The concept of "virus sovereignty" proposed by Indonesia in 2007 challenges the international tradition of virus sharing. In the context of the global outbreak of coronavirus disease 2019, the issue of virus sharing has become an important topic in the reform of the global health governance mechanisms. Virus sharing is an important guarantee of dealing with major global infectious diseases. However, the emergence of the concept of "virus sovereignty" shows that there are defects in the operation of virus sharing mechanism in the international community. The "virus sovereignty" problem is an ethical issue essentially, involving asymmetric interests hindering unity and cooperation, intellectual property rights expansion challenging the principle of solidarity, and excessive self-defense amplifying utility risks. "Community of common health for mankind" provides a constructive and feasible option to solve the dilemma of "virus sovereignty".

Application and effect of partnership plan competition in the recruitment of apheresis platelet donation / 中国输血杂志

【Objective】 To analyze the demographic characteristics of apheresis platelet donors who participated in the Partnership Plan Competition(PPC) of Beijing Red Cross Blood Center, and to analyze the effect of publicity and recruitment of apheresis platelet donors, so as to provide reference for formulating recruitment strategy of apheresis platelet donation. 【Methods】 Apheresis blood donors who participated in PPC from March 18, 2021 to May 18, 2021 were selected as research subjects, and their demographic data in terms of gender, age, occupation and education, and relevant blood donation data within 12 months such as the number of blood donations, whether they were regular blood donors were collected. The demographic characteristics of PPC donors and promising groups were analyzed. 【Results】 There were 58 recruiters participating in the PPC, and a total of 170 people were recruited; 53.53%(91/170) successfully participated in the donation of apheresis platelets, and 35.16%(32/91) became regular blood donors. Those 18-30 years old college male students were promising group in the PPC, and were more willing to participate in the recruitment and donation of apheresis platelets. 【Conclusion】 The PPC has significant effect on the promotion and recruitment of apheresis platelets donation. Measures such as setting the types of souvenirs according to the preferences of promising groups, strengthening publicity of PPC, encouraging non-blood donors to participate and expanding targeted recruitment can be taken in the future to increase the success rate of blood donation of the recruitment.

Study on the correlation between positive psychological capital and communication ability of phlebotomist in Beijing / 中国输血杂志

【Objective】 To analyze the relevant factors affecting the positive psychological capital and communication ability of phlebotomist in blood stations based on the theory of positive psychology and communication behavior, so as to provide reference for the development of professional nursing work in blood stations. 【Methods】 According to the Extensive Positive Psychological Capital Questionnaire and Zeng Kai′s Blood Donor Nurses Communication Ability Evaluation Scale, an online survey was conducted by WJX (a platform providing functions equivalent to Amazon Mechanical Turk) and statistical analysis was performed using SPSS25.0. 【Results】 The average score of positive psychological capital among phlebotomists was 4.78±0.75, with four dimensions (from high to low) as optimism 5.23±1.09, hope 4.9±0.92, self-efficacy 4.57±0.88 and resilience 4.52±0.69 (P0.05). There was a positive correlation between positive psychological capital and communication ability of phlebotomists(P<0.01). The academic qualifications, professional titles, training frequency and knowledge of self-perception are the factors affecting the positive psychological capital and communication ability of phlebotomists.. 【Conclusion】 Managers in blood collection and supply institutions should encourge phlebotomists to study, think and practice initiatively, and conduct education and training on psychological and professional quality of phlebotomists continuously.

Effects of Dayuanyin decoction on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome / 中国药房

OBJECTIVE To study the effects of Dayuanyin decoction （DYY） on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome. METHODS Thirty-six BALB/c mice were divided into the normal group （NC group）， model group （MC group）， positive control group （LBM group， 57.59 mg/kg ribavirin）， DYY low-dose， medium-dose and high-dose groups （LDYY，MDYY，HDYY groups，1.67，3.34，6.68 g/kg，calculated by crude drug）， with 6 mice in each group. Except for NC group， RSV-Hanshi yufei syndrome model was induced by “Hanshi modeling+RSV infection”； after the second cold and wet stimulation， RSV solution was dripped into the nasal cavity at 50% tissue culture infectious dose， once a day， for 3 consecutive days； each administration group was given corresponding solution intragastrically 4 hours after each nasal drip， once a day， for 5 consecutive days. The levels of motilin （MTL） and gastrin （GAS） in serum， the levels of IL-6 and IL-1β in supernatant of lung tissue， and the percentage of peripheral blood lymphocytes were all determined. The pathological changes of lungs were observed， and the changes of gut microbiota were analyzed. RESULTS Compared with MC group， the levels of MTL in serum （except for HDYY group）， and the levels of IL-6 and IL-1β in supernatant of lung tissue were all decreased significantly in DYY groups， while the level of GAS （except for HDYY group） in serum was increased significantly （P＜0.05 or P＜0.01）. The pathology of lung tissue was improved， the percentage of T lymphocytes in LDYY group and the percentages of T lymphocyte and B lymphocyte in MDYY group were all increased significantly （P＜0.05 or P＜0.01）. Compared with the NC group， Bacteroidetes， Actinobacteria， Bacteroides， Alistipes， Bacteroidota， Bacteroides acidfaciens and Alloprevotella were expressed in high abundance， while Firmicutes， Proteobacteria， Lachnospiraceae NK4A136 group， Kineothrix and Clostridiales unclassified were expressed in low abundance. After the intervention of medium-dose DYY， the relative abundance of each microbiota tended to be adjusted back， with different species including Lachnospiraceae_UCG-Ruminococcus， etc. CONCLUSIONS Dayuanyin decoctioncan reduce the lung injury caused by RSV， the mechanism of which may be associated with relieving inflammation， regulating gastrointestinal hormone levels， the percentage of lymphocytes and the abundance of beneficial and harmful bacteria in the intestinal tract.

Clinical characteristics and meteorological factors of patients with chronic heart failure in Qinghai plateau area / 公共卫生与预防医学

Objective To analyze the clinical characteristics and meteorological factors of patients with chronic heart failure (CHF) in Qinghai Plateau area, and to provide a theoretical basis for the diagnosis and treatment of patients with chronic heart failure. Methods A total of 356 patients with CHF admitted to our hospital in Qinghai Plateau area from 2019 to 2020 were selected, and the number of cases, age, gender, comorbidity, NYHA cardiac function classification of CHF patients in Qinghai Plateau area from 2019 to 2020 were counted. To compare NYHA cardiac function classification and underlying diseases in CHF patients at different ages and altitudes in Qinghai Plateau area. The daily average temperature (℃), daily temperature and daily range (℃), daily average wind speed (m/s), daily average air pressure (kPa) and daily average relative humidity (%) in Qinghai Plateau from 2019 to 2020 were collected. According to the general clinical data of patients, the changes of the monthly incidence of CHF patients were analyzed. Pearson correlation analysis was used to compare the correlation between the monthly incidence of CHF patients and meteorological factors, and to explore the influence of meteorological factors on the incidence of CHD in Qinghai Plateau. Results Among the 356 CHF patients, there were 181 males and 175 females, with an average age of (72.47 ±6.49) years old. The NYHA classification of cardiac function was grade II in 103 cases, grade ⅲ in 198 cases, and grade ⅳ in 55 cases. NYHA cardiac function classification increased with age, and there was significant difference in NYHA cardiac function classification among CHF patients of different ages (P<0.05). Among 356 CHF patients, 91 cases (25.56%) were complicated with hypertension, 63 cases (17.70%) were complicated with coronary heart disease, 57 cases (16.01%) were complicated with diabetes, and 40 cases (11.24%) were complicated with hypergenic heart disease. 25 cases (7.02%) were complicated with heart valve disease. Hypertension, coronary heart disease, diabetes mellitus, hypergenic heart disease and valvular heart disease increased with age, and there were statistically significant differences between CHF patients with different ages and underlying diseases (P<0.05). CHF patients in Qinghai Plateau region were mainly concentrated in January-March and October-December. Taking the number of CHD admissions as the dependent variable and each meteorological factor as the independent variable, the correlation between each factor was compared. The results showed that the number of CHF cases was positively correlated with the daily temperature range and daily mean air pressure, and negatively correlated with the average daily temperature (P<0.05). Daily temperature range (OR=2.61) and daily mean air pressure (OR=1.89) were independent risk factors for CHF in Qinghai Plateau area (P<0.05). Conclusion CHF is more prevalent in elderly people in high altitude areas in Qinghai Plateau. For months with high temperature changes, wind speed, we should pay attention to weather changes and take preventive measures in advance.

Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through A β/Kv2.1/microglial NLRP3/neuronal tau axis / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Bacterial community diversity in Dermatophagoides farinae using high-throughput sequencing / 中国血吸虫病防治杂志

Objective To investigate the bacterial community diversity in Dermatophagoides farinae. Methods Laboratory-cultured D. farinae was collected, and the composition of microbial communities was determined by sequence analyses of the V4 region in the bacterial 16S ribosomal RNA (16S rRNA) gene on an Illumina PE250 high-throughput sequencing platform. Following quality control and filtering of the raw sequence files, valid reads were obtained and subjected to operational taxonomic units (OTU) clustering and analysis of the composition of microbial communities and alpha diversity index using the Usearch software, Silva database, and Mothur software. Results A total of 187 616 valid reads were obtained, and 469 OTUs were clustered based on a sequence similarity of more than 97%. OTU annotation showed that the bacteria in D. farinae belonged to 26 phyla, 43 classes, 100 orders, 167 families and 284 genera. The bacteria in D. farinae were mainly annotated to five phyla of Proteobacteria, Firmicutes, Bacteroidota, Actinobacteriota, and Acidobacteriota, with Proteobacteria as the dominant phylum, and mainly annotated to five dominant genera of Ralstonia, norank-f-Mitochondria, Staphylococcus and Sphingomonas, with Wolbachia identified in the non-dominant genus. Conclusions A high diversity is identified in the composition of the bacterial community in D. farinae, and there are differences in bacterial community diversity and abundance among D. farinae.

Clinical study on the mediating effects of social support on the burden of primary caregivers for Parkinson's patients and their quality of life / 中华老年医学杂志

Objective:To examine the burden of caregivers for elderly Parkinson's patients(PD)and to analyze the mediating effects of social support on primary PD caregivers' burden and their quality of life.Methods:In this cross-sectional study, 281 primary caregivers for elderly Parkinson's patients who visited the Department of Neurology's outpatient clinics of Qilu Hospital of Shandong University from January to May 2021 were surveyed via a convenience sampling method, with 242 valid questionnaires(86.1%). The Chinese versions of the Caregiver Burden Questionnaire, Social Support Rating Scale and 36-Item Short Form Health Survey were used for the investigation.Pearson correlation analysis was used to establish a structural equation model for the influence of social support in the burden and quality of life of caregivers for PD patients.The mediating effects were tested using Process v2.16.3 and re-tested using AMOS.The mediating effects were validated with Bootstrap.Results:Primary caregivers' scores on burden, social support and quality of life were(26.9±23.1), (40.5±8.7)and(593.7±163.3), respectively.Caregiver burden was negatively correlated with social support(r=-0.482, P<0.01), and social support was positively correlated with quality of life(r=0.513, P<0.01). Caregiver burden was negatively correlated with quality of life( r=-0.654, P<0.01), The validated mediating effects showed caregiver burden's direct effects on quality of life(95% CI: -0.38-0.61)and mediating effects of social support(95% CI: -0.08-0.21), not including 0, indicating that the care burden of primary caregivers for elderly PD patients was not only able to predict their quality of life, but also predict their quality of life through the mediating effects of social support(direct effect: -0.50 and mediating effect: -0.14, accounting for 78.0% and 22.0%, respectively, of the total effect of -0.64). Conclusions:Care burden and social support are important factors affecting the quality of life of primary caregivers for elderly PD patients.Reducing care burden can not only directly affect the quality of life, but also indirectly affect the quality of life by increasing social support.

Application of wound dressing training based on Thorndike's learning theory in clinical nursing education / 中华医学教育探索杂志

Objective:To explore the effect of applying the wound dressing training based on Thorndike's learning theory (WCTT) in clinical nursing education.Methods:The study conducted controlled trial among nursing interns selected from Thyroid Surgery Department of West China Hospital of Sichuan University, and the nursing students were divided into the experimental group ( n=51) and the control group ( n=49). Nursing students in the experimental group were trained with WCTT, while the control group adopted the traditional teaching. Two groups were investigated by the ability of wound dressing questionnaire and were examined on the practical wound dressing operation to evaluate the teaching effect. SPSS 20.0 was used for statistical analysis. Results:Nursing students in the experimental group showed a higher self-evaluation on such aspects as understanding, interests, theoretical mastery, evaluation of wounds, practical skills, independence, fulfillment and model assessment. Meanwhile, the experimental group had a higher score of practical wound dressing operation than the control group [(93.25±2.11) points vs. (90.06±2.43) points] ( P<0.05). Conclusion:In clinical nursing teaching, WCTT could improve the wound dressing ability, independence and enthusiasm of nursing students, and this training mode had a positive effect on the clinical nursing teaching efficiency, which is worth further promotion.

Isolation, identification and electrophysiological activity of BmK M2 from Buthus martensii Karsch venom / 中国药科大学学报

@#This study aimed to isolate and identify novel toxin peptides targeting voltage-gated sodium channels (VGSGs) from the venom of the Buthus martensii Karsch (BmK) scorpion. Using G50-gel filtration, HPLC, peptide fingerprinting and amino acid sequencing, a novel sodium channel modulator, BmK M2, was identified from BMK scorpion. BmK M2 is a relatively abundant long chain polypeptide toxin in BmK scorpion venom with a molecular weight of 7 235.59, consisting of 64 amino acids and 4 pairs of disulfide bonds.Sequence alignment showed that the amino acid sequence of BmK M2 had high sequence and structural similarity to that of the discovered sodium channel toxins of BmK M1, BmK M3 and BmK M9, etc.BmK M2 is a potential new sodium channel modulator.Electrophysiological results revealed that BmK M2 can significantly enhance the activation, delay the steady-state inactivation and closed-state inactivation of Nav1.7, but has no activity on Nav1.8.BmK M2 can be used as a novel peptide probe for the study of the structure and function of Nav1.7 and the development of drugs targeting Nav1.7.

Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

Analysis of correlation between serum homocysteine level and severity of coronary heart disease / 公共卫生与预防医学

Objective To observe the correlation and clinical significance between serum homocysteine (HCY) level and the severity of coronary heart disease (CHD). Methods A total of 497 hospital-based patients with newly diagnosed coronary heart disease from June 2018 to June 2021 in our hospital were selected as the study subjects. The patients' sociodemographic information, coronary heart disease condition information and HCY level information at diagnosis were collected. The correlation between serum HCY level and the severity of coronary heart disease was analyzed from multiple perspectives. Data were collected and analyzed using SPSS 19.0 statistical software package. Results The average level of HCY in all patients was (20.23±2.18) μmol/L, among which 330 cases exceeded the standard level of HCY and 167 cases did not exceed the standard level. There were statistically significant differences in serum HCY levels among patients with different genders, different ages, different altitudes, and different types of coronary heart disease (P<0.05). The correlation coefficients between HCY level and the severity of CHD in different genders were r1=0.356, and r2 =0.198, P<0.05. The correlation coefficients between HCY level and the severity of CHD in patients of different ages were r1=0.304, r2=0.50, r3=0.217, and r4=0.185, P<0.05. The correlation coefficients between HCY level and the severity of CHD in patients living at different altitudes were r1=0.129, r2=0.369, and r3 =0.473, P<0.05. The correlation coefficients between HCY level and the severity of CHD in patients with different types of CHD was r1=0.137, r2=0.200, and r3=0.205, P<0.05. Logistic multivariate regression analysis showed that serum HCY, altitude, gender and age were independent risk factors for coronary heart disease (P<0.05). Conclusion The correlation between serum HCY level and the severity of CHD is stronger in male patients than in female patients. The correlation between HCY level and the severity of CHD was strongest in patients aged 40-50. Serum HCY level is more strongly correlated with the severity of CHD in patients with high altitude. Serum HCY test can be used to diagnose CHD and evaluate the severity of coronary artery disease.

Research progress on pesticide residues of Lonicera Japonica Flos / 中国中药杂志

Lonicera Japonica Flos is the dried bud or nascent flower of Lonicera japonica(Caprifoliaceae). The plant suffers from various diseases and pests in the growth period and thus pesticides are often used. As a result, the resultant pesticide residues in Lonicera Japonica Flos have aroused great concern. This review summarized the investigation, detection methods, content analysis, and risk assessment of pesticide residues in Lonicera Japonica Flos since 1996, and compared the maximum residue limits among different countries and regions. The results showed that the pesticide residues were detected in Lonicera Japonica Flos from different production areas, and only some exceeded the limits. The residual pesticides have changed from organochlorines to new types such as tebuconazole and nitenpyram. The detection method has upgraded from chromatography to chromatography-mass spectrometry. Most pesticide residues will not cause health risks, except carbofuran. Pesticide residues limit the development of Lonicera Japonica Flos industry in China. In practice, we should improve the drug registration of Lonicera Japonica Flos, promote ecological prevention and control technology, and formulate and promote pesticide residue limit standard of Lonicera Japonica Flos.

Research progress on pesticide residues of Panacis Quinquefolii Radix / 中国中药杂志

Panacis Quinquefolii Radix is the dry root of Panax quinquefolium, which is a perennial plant of Araliaceae. The plant has a long growth cycle and serious growth barrier problem, which leads to the use of pesticides. As a result, the pesticide residues in Panacis Quinquefolii Radix are arousing great concern. This paper reviews the research findings on the investigation, detection methods, content analysis and risk assessment of pesticide residues in Panacis Quinquefolii Radix since 1993, and compares the pesticide residue limit standards of different countries and regions. The pesticide residues in Panacis Quinquefolii Radix have been changing from organochlorines with high toxicity to triazines and triazoles with low toxicity. The pesticide residues are generally low, while the pollution of pentachloronitrobenzene and other pesticides still exist. The detection method has evolved from chromatography to chromatography-mass spectrometry. There are no reports of health risks caused by pesticide residues of Panacis Quinquefolii Radix. Pesticide residue is a major factor restricting the sound development of Panacis Quinquefolii Radix industry in China. Therefore, we suggest to improve the registration of pesticides applied to the plant, popularize mature ecological planting mode and supporting technology, and strengthen the research on the risk assessment and limit standard of pesticide residue in Panacis Quinquefolii Radix.