Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Clinical efficacy of PDCA cycle management model cycle management combined with pulsed tooth punch applied in maintenance period of patients with moderate to severe periodontitis / 吉林大学学报(医学版)

Objective:To observe the clinical efficacy of plan-do-check-Act(PDCA)cycle management model combined with pulsed tooth punch applied in maintenance period of the patients with moderate to severe periodontitis,and to provide the theoretical basis for application of the PDCA cycle management model in the periodontitis patients.Methods:A total of 50 patients with moderate to severe periodontitis were selected based on predefined inclusion,exclusion,and elimination criteria.The patients were randomly divided into experiment group(n=25)and control group(n=25).The patients in experiment group underwent maintenance care with pulsed tooth punch in combination with the BASS brushing technique,while the patients in control group maintained oral hygiene with the BASS brushing technique alone.The patients in both two groups were managed with the PDCA cycle management model.The patients were asked to return for follow-up visits at 2,4,8,and 12 weeks of self-care,and the personalized corrections and guidance were provided based on the plaque accumulation.The clinical periodontal parameters,including plaque index(PLI),probing depth(PD),and bleeding index(BI),at 4 and 12 weeks of self-care,as well as the levels of tumor necrosis factor-α(TNF-α)and interleukin-17(IL-17)in the gingival crevicular fluid of the patients in two groups were observed and recorded.Results:After 4 and 12 weeks of self-care,compared with control group,the PLI,PD,and BI of the patients in experiment group were significantly decreased(P<0.01);compared with baseline,the PLI,PD,and BI of the patients in both two groups at 4 and 12 weeks of self-care were increased(P<0.05 or P<0.01);Compared with 4 weeks of self-care,the PLI,PD,and BI of the patients at 12 weeks of self-care were increased(P<0.01).After 4 and 12 weeks of self-care,compared with control group,the levels of TNF-α and IL-17 in gingival crevicular fluid of the patients in experiment group were significantly decreased(P<0.01);compared with baseline,the levels of TNF-α and IL-17 in gingival crevicular fluid of the patients in two groups at 4 and 12 weeks of self-care were increased(P<0.01).Conclusion:The use of pulsed tooth punch under the PDCA cycle management model can significantly decrease the PLI,PD,BI,and the levels of inflammatory factors in gingival crevicular fluid of the patients with moderate to severe periodontitis,and inhibit the plaque formation and control the gingival inflammation,benefite the maintenance of efficacy of the patients with moderate to severe periodontitis.

Improved effect and mechanism of propofol on vascular hyporeactivity in septic rats / 陆军军医大学学报

Objective To observe the improved effect of propofol on vascular hyporeactivity in septic rats and its underlying mechanism.Methods A total of 96 SD rats(12 weeks old,both genders,weighing 200～220 g)were randomly divided into sham group(n=16),sepsis group(n=16,cecal ligation and puncture),propofol group(n=16),propofol+ROCK inhibitor Y-27632 group(n=16),propofol+PKCαinhibitor GO6976 group(n=16),propofol+IP3 inhibitor 2-APB group(n=8)and propofol+gap junction inhibitor metoclopramide sodium(Movens)group(n=8).In vitro vascular ring reactivity and vascular calcium sensitivity were measured to observe the improved effects of propofol on vascular hyporeactivity in septic rats and its relationships with RhoA/ROCK,PKCα,IP3 and cell gap junction.Results Determination of in vitro vascular ring and calcium sensitivity showed that the contractile reactivity to norepinephrine(NE)and to calcium sensitivity were significantly decreased in the arterial rings isolated from the septic rats compared with those from the sham group,with the dose-response curve shifting to the right,and most significant decrease by 51.42％in the superior mesenteric artery(SMA,P＜0.05).Propofol treatment significantly improved the hyporeactivity and calcium sensitivity of the vessels isolated from the septic rats,especially those of the femoral artery with a recovery rate of 89.57％(P＜0.05).In comparison with the propofol group,the dose-response curves of the propofol+Y-27632 group and the propofol+GO6976 group were shifting to right,indicating that Y-27632 and GO6976 could significantly inhibit the amelioration of propofol on calcium sensitivity of SMA in severely septic rats with an inhibitory rate of 146.95％and 88.63％(P＜0.05),respectively.Isolated vascular reactivity measurement demonstrated that Y-27632 and Movens treatment significantly antagonized the ameliorated role of propofol on hyporeactivity of blood vessels from the septic rats with an inhibitory rate of 40.79％and 169.90％(P＜0.05),separately,while no such effect was observed in the propofol+GO6976 and propofol+2-APB groups.Conclusion Propofol treatment can significantly improve vascular hyporeactivity of septic rats,which may attribute to the increase of vascular calcium sensitivity through RhoA/ROCK pathway.

Research Advance on Smartphone-based Visual Biosensor in Point-of-Care Testing / 分析化学

Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.

Clinical Efficacy of Withdrawal Therapy Based on Regulating Nutritive Qi and Defensive Qiin Treating Sedative-Hypnotic Dependent Insomnia of Disharmony Between Nutritive Qiand Defensive Qi Type / 广州中医药大学学报

Objective To observe the clinical efficacy of withdrawal therapy based on regulating nutritive qi and defensive qi(shortened to Tiaohe Yingwei method)in treating sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.Methods Ninety patients with sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type were randomly divided into the treatment group and the control group,with 45 patients in each group.The control group was given oral use of Estazolam by 25%of weekly dose-reduction,while the treatment group was treated with Chinese medicinal decoction of Tiaohe Yingwei Zhumian Prescription based on Tiaohe Yingwei method together with Estazolam.The treatment course for the two groups lasted for 4 weeks.The changes of Pittsburgh Sleep Quality Index(PSQI)scores,total TCM syndrome scores,and Drug-withdrawal Syndrome Scale(DWSS)scores in the two groups were observed before and after treatment.After treatment,the efficacy for improving sleep efficiency value(IUSEV)and clinical safety in the two groups were evaluated.Results(1)During the trial,2 cases fell off in the treatment group,and 43 cases included in the statistics;3 cases fell off in the control group,and 42 cases included in the statistics.(2)After 4 weeks of treatment,the total effective rate for improving IUSEV of the treatment group was 88.37%(38/43),and that of the control group was 61.90%(26/42).The intergroup comparison by non-parametric rank-sum test showed that the efficacy for improving IUSEV in the treatment group was significantly superior to that in the control group(P＜0.05).(3)After treatment,obvious reduction was shown in the overall PSQI scores and the scores of the items of sleep quality,time for falling asleep,sleep time,sleep efficiency,sleep disorder and daytime dysfunction in the two groups when compared with those before treatment(P＜0.05).The intergroup comparison showed that except for the items of sleep disorder and daytime dysfunction,the treatment group had stronger effect on decreasing the scores of the remaining items and the overall PSQI scores than the control group(P＜0.05).(4)After treatment,the total scores of TCM syndromes of both groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the total scores of TCM syndrome in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the total DWSS scores of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(6)During the course of treatment,no significant adverse reactions occurred in the two groups,or no abnormal changes were found in the safety indexes such as routine test of blood,urine and stool,liver and kidney function,and electrocardiogram of the patients.Conclusion Withdrawal therapy based on Tiaohe Yingwei method exerts certain effect for the treatment of sedative-hypnotic dependent insomnia of disharmony between nutritive qi and defensive qi type.The therapy is effective on improving the quality of sleep and reducing the incidence of drug-withdrawal syndrome,and has a high safety.

Comparison of Methods for Generating Thrombotic Models after the Endothelial Injury / 昆明医科大学学报

Objective Endothelial injury plays a crucial role in forming deep vein thrombosis.This study aims to compare the effectiveness of various methods for creating rabbit femoral vein thrombotic models after the endothelial injuryso as to provide a solid experimental foundation for further research on the endothelial injury and deep vein thrombosis.Methods Forty-five rabbits were randomly divided into three groups(A,B,C),with 15 cases in each group and subjected to the endothelial injury using the methods of simple clamping,combined complete ligation,and combined incomplete ligation,respectively.The intravascular ultrasonic manifestations and local endothelial pathological changes were compared at 1,3,and 7 days after modeling.Results Significant differences in vascular diameter and Young's modulus values were observed after 7 days of modeling(P<0.05).In pairwise comparisons between the groups,the Young's modulus values in group C were significantly higher than those in groups A and B after 7 days of modeling(P<0.05).Pathological examination confirmed the presence of fibr-inoid thrombus in the blood vessels of group C on the seventh day of modeling.Conclusion Combining simple clam-ping and incomplete ligation can produce a relatively stable endothelial injury and thrombus formation.This method provides a robust experimental model for further investigation into deep vein thrombosis after the endothelial injury.

A Study of Factors Influencing the Use Behaviour of Elderly Patients in Smart Medical Services Based on Decision-making Trial and Evaluation Laboratory / 中国医院管理

Objective To identify and analyze the key factors affecting the use behavior of elderly patients with smart medical services by taking the smart medical system of a top-three hospital as an example,so as to provide a basis for promoting the use of smart medical services for elderly patients and the age-appropriate transformation of smart medical services.Methods The factors influencing the use behavior of elderly patients with smart medical services were analyzed,and correlation analysis of factors influencing the use behaviour of elderly patients with smart medical services were analyzed by DEMATEL method.Results The centrality and causation of all influencing factors were calculated,and the key influencing factors affecting the use behavior of elderly patients with smart medical services were identified.Among them,the main factors of reason degree are the hospital's willingness to adapt to aging transformation,the influence of key population and relevant national policy support,and the main factor of center degree is the perceived cost of patients.Conclusion The perceived cost of elderly patients can be reduced by improving the smart medical service,enhancing the health information literacy of elderly patients and giving full play to the social support effect,so as to promote the use behavior of elderly patients'smart medical services.

Construction of domain knowledge graph of dementia care / 中华护理杂志

Objective To construct a domain knowledge graph of dementia care,so as to provide the foundation and guarantee for the next intelligent application based on the knowledge graph.Methods A top-down approach was adopted to construct a domain knowledge graph of dementia care.Firstly,the ontology concept is constructed from the top level,namely the schema layer of knowledge graph.Then,instances are filled,and knowledge extraction is carried out from the existing data sources,and the extracted entities and relationships are filled into the pattern layer ontology database to complete the data layer construction of the knowledge graph.Finally,the"entity relationship entity"triplet data was input into the Neo4j graph database for storage.Results In this study,the personalized care plan set of 1 012 dementia cases was used as the corpus to construct a domain knowledge graph of dementia care.The knowledge graph takes people with dementia as the core,and unfolds,one by one,around basic characteristics,care problems,and care plans in a standardized"entity-relationship-entity"triplet format,forming a large knowledge network,which contains a total of 1 522 specific dementia care knowledge entities and 8 kinds of inter-entity relationships.Conclusion The domain knowledge graph of dementia care constructed in this study clearly and intuitively shows the global pedigree and logical path of knowledge,which provides an efficient and intelligent basic guarantee for the browsing,retrieval and application of dementia care knowledge,so as to realize personalized and intelligent management of people with dementia,break through the bottleneck of lack of professionals,improve the health outcomes of people with dementia,promote the implementation of inclusive pension services,and promote healthy aging.

Association of gene polymorphisms in microRNA with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 To investigate the relationship of miRNA gene polymorphisms with blood pressure (BP) responses to the sodium and potassium diet intervention. 【Methods】 In 2004, we recruited 514 participants from 124 families in seven villages of Baoji, Shaanxi Province, China. All subjects were given a three-day normal diet, followed by a seven-day low-salt diet, a seven-day high-salt diet, and finally a seven-day high-salt and potassium supplementation. A total of 19 miRNA single nucleotide polymorphisms (SNPs) were selected for analysis. 【Results】 Throughout the sodium-potassium dietary intervention, the BP of the subjects fluctuated across all phases, showing a decrease during the low-salt period and an increase during the high-salt period, followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet. MiR-210-3p SNP rs12364149 was significantly associated with systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) responses to low-salt diet. MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention. In addition, miR-26b-3p SNP rs115254818 was significantly correlated with SBP, DBP and MAP responses to high-salt intervention. MiR-1307-5p SNPs rs11191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet. MiR-4638-3p SNP rs6601178, miR-210-3p SNP rs12364149, miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet. In addition, miR-26b-3p SNP rs115254818 was significantly associated with SBP, DBP and MAP responses to potassium supplementation. MiR-1307-5p SNPs rs11191676, rs2292807, and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation. 【Conclusion】 miRNA gene polymorphisms are associated with BP response to sodium and potassium, suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.

Associations of genetic variants in GLP-1R with blood pressure responses to dietary sodium and potassium interventions / 西安交通大学学报(医学版)

【Objective】 To investigate the association between genetic variations in the glucagon-like peptide-1 receptor (GLP-1R) gene and BP responses to sodium and potassium intake. 【Methods】 A total of 514 subjects from 124 families were recruited in Meixian County, Shaanxi Province, in 2004, resulting in the establishment of a "salt-sensitive hypertension study cohort" . The subjects followed a dietary regimen which involved a normal diet for 3 days, a low-salt diet for 7 days, a high-salt diet for 7 days, and a high-salt potassium-supplemented diet for 7 days. BP measurement was conducted at different intervention periods, and peripheral blood samples were collected. Additionally, eight single nucleotide polymorphisms (SNPs) of the GLP-1R gene were genotyped using the MassARRAY detection platform. 【Results】 The GLP-1R gene SNP rs9462472 exhibited a significant association with systolic BP, diastolic BP, and mean arterial pressure response to high-salt intervention. Similarly, SNP rs2268637 showed a significant association with systolic BP response to high-salt intervention. Furthermore, SNP rs2268637 was significantly associated with systolic BP and mean arterial pressure responses to high-salt plus potassium supplementation intervention. 【Conclusion】 Our findings indicate a significant association of genetic variations in the GLP-1R gene with BP responses to sodium and potassium intake. This suggests that the GLP-1R gene plays a role in the regulation of BP salt sensitivity and potassium sensitivity.

Interpretation and implementation reflection on the Measures for Scientific and Technological Ethics Review （for Trial Implementation） / 中国医学伦理学

Nowadays， both international and domestic scientific and technological innovation activities are facing different types and degrees of ethical risks， which bring many negative impacts to human society and even threaten the safety of individuals’ lives and properties. To further standardize the ethics review of science and technology， strengthen risk prevention and control， and promote responsible innovation， ten ministries and commissions jointly issued the Measures for Scientific and Technological Ethics Review （for Trial Implementation） in September 2023. The Measures for Scientific and Technological Ethics Review （for Trial Implementation） required that ethical review should be implemented for science and technology innovation activities in many fields， ethical review should be more practicable. It strengthened emergency management of major public emergencies， proposed that research institutions should establish risk assessment methods， new unorganized personnel can apply for entrusted ethical review， and an ethics committee certification system should be established. The Measures for Scientific and Technological Ethics Review （for Trial Implementation） had outstanding highlights and distinctive features， clarified the responsible parties for scientific and technological innovation activities， strengthened their responsibilities and management of ethical review， introduced a management system for the list of scientific and technological activities， and created an expert review model for addressing the challenges of greater ethical risks. The interpretation and implementation reflection on the Measures for Scientific and Technological Ethics Review （for Trial Implementation） can provide a reference for the implementation of it， with a view to promoting the ethical review of science and technology as a normative force， as well as facilitating the upward and positive development of scientific and technological innovation activities for the benefit of humanity.

Association between residual cholesterol and the risk of subclinical renal damage / 西安交通大学学报(医学版)

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

Associations of genetic polymorphisms in Corin with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Tumor cell-based glycolytic metabolism and single-cell sequencing of urinary exfoliated cells for the diagnosis and molecular profiling of urothelial carcinoma / 中华病理学杂志

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.

Clinical observation of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in patients with acute heart failure / 中华内科杂志

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.

Correlation analysis between serum FOXP1 and CDK2 levels and the occurrence of osteoporosis in perimenopausal women / 中华内分泌外科杂志

Objective:To investigate the correlation between serum forkhead box protein P1 (FOXP1) and cyclin-dependent kinase2 (CDK2) and bone mineral density in perimenopausal women with osteoporosis (OP) .Methods:A total of 80 perimenopausal women treated in our hospital from Feb. 2021 to Aug. 2022 were selected as study objects. Among them, 38 were in the OP group and 42 were in the control group. The expression levels of FOXP1 and CDK2 in serum were detected by ELISA. BMD expression levels of lumbar spine (L1-L4) and femoral neck were measured by DEXA BMD analyzer. The correlation between serum FOXP1 and CDK2 and bone mineral density in perimenopausal women with osteoporosis was analyzed by Pearson method.Results:Compared with the control group, the contents of FOXP1 and CDK2 in serum of the control group were (42.94±3.37) pg/ml and (102.46±12.247) pg/ml, respectively. Serum FOXP1 and CDK2 contents in OP group were (25.91±4.38) pg/ml and (60.59±10.777) pg/ml, respectively. Compared with the control group, serum FOXP1 and CDK2 expression levels and bone mineral density of lumbar spine (L1-L4) and femoral neck in OP group were significantly decreased. The BMD of lumbar spine (L1-L4) and femoral neck of women in the control group were 0.68±0.28 and 0.43±0.99, respectively. BMD of lumbar spine (L1-L4) and femoral neck of women in the OP group were 0.40±0.10 and 0.21±0.15, respectively. Bone mineral density decreased in the lumbar spine (L1-L4) and femoral neck in the OP group. The differences were statistically significant ( P<0.05). In addition, the correlation analysis results showed that the expression level of FOXP1 in serum was positively correlated with bone mineral density of lumbar spine (L1-L4) and femoral neck ( r=0.546, 0.245, P<0.05), and the expression level of CDK2 was positively correlated with bone mineral density of lumbar spine (L1-L4) ( r=0.600, P<0.05) . Conclusions:In perimenopausal women with osteoporosis, the expression of FOXP1 and CDK2 in serum was significantly decreased, and there was a correlation with bone mineral density. It is suggested that FOXP1 and CDK2 may be used as biological indicators and clinical predictors of osteoporosis in perimenopausal women.

Effect of ursolic acid extracted from Hippophae Rhamnoides L.on repair of sciatic nerve injury in rats / 实用医学杂志

Objective To investigate the repairing effect of ursolic acid extracted from Hippophae rhamnoi-des L.on sciatic nerve injury in rats.Methods After preparing a sciatic nerve damage model,thirty 2-month old Wistar rats were randomly divided into ursolic acid and control groups,with 15 rats in each group.Ursolic acid group was given Ursolic acid 150 mg/(kg·d)by gavage,while the control group was given the same dose of normal saline for 6 weeks.After 6 weeks,H&E staining was used to observe the pathological changes of rat sciatic nerves,and SFI and MNCV were calculated;The expression of NGF in sciatic nerve was detected by immunohistochemistry,and the expression of GAP-43 in L4-L6 spinal cord was detected by Western blotting.Results After 6 weeks,compared to the control group,the number of regenerated nerve fibers in the ursolic acid group increased,the arrangement was slightly regular,the capillary structure was abundant,and the proliferation of fibroblasts decreased;SFI and MNCV%were significantly increased(P<0.05),NGF protein positive expression was significantly increased(P<0.05),and the difference was statistically significant(P<0.05).GAP-43 protein expression in sciatic nerve tissue was significantly increased(P<0.05).Conclusions The intervention of ursolic acid extracted from Hippophae rhamnoides L.can improve the function of rats after sciatic nerve injury,promote the increase of regenerated nerve fibers and the repair of myelin sheath in rats with sciatic nerve injury,which may be related to increased NGF and GAP-43 protein expression in rats.