Tirzepatide: A new glucagon-like peptide-1 receptor/glucose-dependent insulinotropic peptide receptor dual agonist / 中国临床药理学与治疗学

Tirzepatide is the first-in-class dual agonist of glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic peptide (GIP) receptor, which plays a variety of physiological effects by imitating natural GLP-1 and GIP. In the completed large phase III series of clinical studies of SURPASS and SURMOUNT, Tirzepatide has demonstrated excellent effects in decreasing glycosylated hemoglobin, reducing weight, improving blood lipid and other metabolic indicators, and is superior to the currently approved GLP-1 receptor agonist. Gastrointestinal reaction is the most common adverse event of the drug, which is generally mild to moderate, and decreases with continuous administration. On May 13, 2022, Tirzepatide was approved for listing by FDA, the current indication is to improve glycemic control of adult patients with type 2 diabetes (T2D) as an adjunct of diet and exercise. In addition to T2D and obesity, there are also extensive and in-depth studies on other metabolic fields. This paper makes a systematic overview of this.

Advances in Study of Icarrin for Anti-aging and Anti-depression： A Review / 中国实验方剂学杂志

Population aging has become a major feature of the demographic structure of today's society， and anti-aging is currently one of the major areas and hot spots of medical research. Kidney deficiency causes aging is the basic theory of aging in TCM， and kidney tonics have a long history of improving physiological functions and significantly alleviating aging-related diseases. However， the formulation of kidney tonics is complicated and the mechanism of action is still unclear. It is difficult to precisely analyze the targets of disease action and metabolic pathways. The kidney tonic herb Epimedium has the effect of tonifying the kidney and augmenting yang， and is not only used to treat diseases related to kidney deficiency and aging， but also has unique advantages in the treatment of mental and emotional diseases. Modern pharmacological studies have proved that Icarrin， a monomeric component of Epimedium， can produce a wide range of biological functions on cardiovascular system， exercise system， reproductive system， and nervous system， with strong antioxidant， free radical scavenging， and repair of mitochondrial DNA damage， which can anti-aging， anti-depression， and improve immunity， etc. In this paper， we searched databases such as CNKI， Pubmed， Wanfang database， Wipu Chinese journal service platform， and web of science to review the research on Icarrin， a monomeric ingredient that has both anti-aging and anti-depression effects， in order to provide a basis for further research on anti-depression and anti-aging in Chinese medicine.

Effects of miR-141 silencing on renal tubular epithelial cell damage induced by high glucose and Sirt1/Nrf2 signaling pathway / 中华内分泌外科杂志

Objective:To investigate the effect of miR-141 down-regulation on the damage of renal tubular epithelial cell, and further to explore its mechanism.Methods:The renal tubular epithelial cell line HK-2 cells were divided into normal (5.5 mmol/L D-glucose) group, hypertonic group, high glucose (30 mmol/L D-glucose) group, negative control+high glucose group (transfected with NC inhibitor vector) and si-miR-141+high glucose group (transfected with miR-141 inhibitor vector) . Real time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-141. The production of reactive oxygen species (ROS) , cell viability and apoptosis were detected by DCFH-DA fluorescence staining, CCK-8 method and flow cytometry. The expression of Sirt1/Nrf2 signaling pathway related proteins was detected by Western blot. Luciferase reporter gene assay verified the targeting relationship between miR-141 and Sirt1 mRNA.Results:①Compared with the normal group, after transfection with si-miR-141, the relative expression of miR-141 decreased (1.00±0.03 vs 0.52±0.06) , the difference was statistically significant ( F=278.104, P<0.05) ; ② Compared with the normal group [DCFH-DA fluorescence intensity (7.18±0.59) %], the high glucose group [DCFH-DA fluorescence intensity (84.95±3.21) %] cell ROS level was significantly increased, and compared with the high glucose group [DCFH-DA fluorescence intensity (84.95±3.21) %] Compared with the si-miR-141+ high glucose group [DCFH-DA fluorescence intensity (45.10±4.29) %] cell ROS levels were significantly reduced, the difference was statistically significant (all P<0.05) ; ③compared with the normal group (5.13%±0.78) % Compared with the hypertonic group (5.96±0.81) %, the high glucose group (32.76±2.95) % cell apoptosis rate was significantly increased, while the si-miR-141+ high glucose group (17.54%± 2.79) % apoptosis rate was significantly lower in the higher glucose group and the negative control+ high glucose group (33.40%±3.14) %, the difference was statistically significant ( F=221.419, P<0.05) ; ④compared with the normal group (100±3.98) % Compared with the hypertonic group (95.68±5.14) %, the high glucose group (67.24±5.18) % HK-2 cell survival rate was significantly reduced; at the same time, compared with the high glucose group (67.24±5.18) % and Compared with the negative control+ high glucose group (65.33±3.10) %, the si-miR-141+ high glucose group (83.55±5.10) % cell survival rate increased significantly, and the difference was statistically significant ( F=93.008, P<0.05) ; ⑤ Compared with the normal group and the hypertonic group, the expression of Cleaved Caspase 3 protein in the high glucose group increased, while the expression of Sirt1, Nrf2 and HO-1 protein was down-regulated; however, compared with the high glucose group, si- In the miR-141+ high glucose group, Cleaved caspase 3 protein expression decreased, while Sirt1, Nrf2 and HO-1 protein expression increased, the difference was statistically significant (all P<0.05) . Conclusions:Down-regulation of miR-141 can ameliorate high glucose-induced renal tubular epithelial cell damage induced oxidative stress by activating Sirt1/Nrf2 signaling pathway.

Association of IFNL3/IFNL4 polymorphisms with efficacy of highly active antiretroviral therapy in patients with HIV-1 infection / 中华临床感染病杂志

Objective To investigate the associations of IFNL3/IFNL4 single-nucleotide polymorphisms(SNPs)with the efficacy of highly active antiretroviral therapy(HAART)in patients with HIV-1 infection.Methods Sixty-three adult patients with HIV-1 infection receiving HAART for at least 1 year in the First Affiliated Hospital, Zhejiang University School of Medicine were enrolled.HIV-1 RNA loads in plasma and HIV-1 DNA loads in peripheral blood mononuclear cells(PBMCs),and blood SNPs were detected by quantitative polymerase chain reaction(qPCR).Plasma inflammatory cytokines were examined by magnetic beads method,and the CD4 +T and CD8 +T lymphocyte counts in peripheral blood were measured by flow cytometry.According to response to HAART,the patients were classified as low HIV-1 RNA group(viral load <100 copies/mL)and high HIV-1 RNA group(viral load≥100 copies/mL);according to CD4+T lymphocyte counts,the patients were defined as low CD4+T cell group(<250 cells/μL), and high CD4+T cell group(≥250 cells/μL);according to HIV-1 DNA levels,the patients were divided into low(<100 copies/106cells)and high(≥100 copies/106cells)HIV-1 DNA groups.Results Three candidate SNPs rs368234815,rs8099917 and rs4803223 had significantly different distribution between low and high HIV-1 RNA groups(χ2=0.043,0.047 and 0.032,all P<0.05).The levels of interleukin(IL)-10 were declined in the low HIV-1 RNA group(U=4.00,P<0.05);the levels of IL-13 were decreased in the high HIV-1 RNA group and the high HIV-1 DNA group(U=0.00 and 2.00,both P<0.05);the levels of IL-21 were reduced in the high HIV-1 RNA group and in the low CD4 +T cell group(U=3.00 and 2.00, both P<0.05),the levels of IL-28A were decreased in the high HIV-1 RNA group,the high HIV-1 DNA group,and the low CD4 +T cell group(U=3.00, 0.50 and 3.00,P<0.05 or <0.01).In addition, rs368234815 was associated with IL-21 level(H=6.690,P<0.05),the IL-21 level in rs368234815 ΔG/ΔG [131.88(2.66,174.00)]was higher than that in TT/TT[6.79(2.81,26.48)](P<0.05);rs4803223 was correlated with IFN-γlevel(H=6.690, P<0.05),the IFN-γlevel in GG subtype[62.26(19.45, 96.49)]was higher than that in GA subtype[6.98(2.19, 99.14)](P<0.05).Conclusion The polymorphisms of IFNL3/IFNL4 rs368234815, rs8099917 and rs4803223 are associated with efficacy of HAART and immune-associated cytokines levels in patients with HIV-1 infection.

miRNA expression between deep and moderate hypothermia circulatory arrest and its impact on intestinal protection / 中华胸心血管外科杂志

Objective To evaluate the miRNA change between hypothermia circulatory arrest at different temperature and its impact on intestinal protection.Methods Sixteen piglets were randomly(n =4) divided into four groups:deep hypothermia circulatory arrest (DHCA,18℃) group,moderate hypothermia circulatory arrest(MHCA,24℃) group,cardiopulmonary bypass(CPB) group and sham operation(SO) group.They were subjected to 80 min hypothermia circulatory arrest,305 min CPB or thoracotomy,respectively.Pick-and-mix custom miRNA real-time PCR panels were utilized to detect intestinal samples.miRNA expression between DHCA and MHCA were compared directly(DHCA vs.MHCA) and indirectly(DHCA/SO vs.MHCA/SO,DHCA/CPB vs.MHCA/CPB).Results Exposure to DHCA caused less intestinal miRNA dysregulation than MHCA.Besides,seven miRNAs(miR-122,miR-145-5p,miR-421-5p,miR-99a,miR-365-5p,miR-31 and miR-192)were differentially expressed between the two hypothermia circulatory arrest groups.Conclusion Better intestinal miRNA protection was provided by DHCA than MHCA.Intestinal miRNA were differentially expressed between hypothermia circulatory arrest at different temperature.

Neuroprotection of selective antegrade cerebral perfusion on pig model exposed to deep hypothermia circulatory arrest / 实用医学杂志

Objective To explore the expression of TLR4/NF-κB pathway in cerebral injury resulting from DHCA ( deep hypothermia circulatory arrest ) as well as the effect of SACP ( selective antegrade cerebral perfusion). Methods Twelve pigs were randomly assigned to DHCA group (n = 6) or SACP group (n = 6) at 18 ℃ for 80 min. IL-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 was determined through qRT-PCR and Western blot. Results Serum IL-6 level of SACP group was significantly lower at the end of circulation arrest and experiment and apoptotic index and NF-κB protein were apparently lower in SACP group (P < 0.05). The level of TLR4 protein and mRNA from SACP group decreased significantly (P < 0.05). Conclusions TLR4/NF-κB pathway plays a critical role in pathogenesis of DHCA cerebral injury and attenuating TLR4/NF-κB cytokines probably contributes to neuroprotection of SACP. TLR4/NF-κB pathway may be a novel target for DHCA.

Rosuvastatin control CIAKI risk on diabetic patients with mild to moderate CKD and diuretics at high risk / 中国生化药物杂志

Objective To assess the application of rosuvastatin control contrast induced acute kidney injury (CIAKI) risk on diabetes mellitus (DM) patients with mild to moderate chronic kidney disease (CKD) and diuretics at high risk.Methods One hundred T2DM patients with mild to moderate CKD scheduled for coronary or peripheral vascular interventional diagnosis selected from May 2013 to June 2015 in endocrinology department of Zhejiang Huzhou Central Hospital and perioperative routine use of diuretics were randomly divided into observation group (51 cases) and control group (49 cases).The observation group received rosuvastatin at draught of night, 10mg per time and needed to take at least 2 times and then performed medical surgery, after surgery, continued to receive rosuvastatin for 3 d, and the total number of days taking rosuvastatin were not less than 5 d;control group not received any statins pre-and post-operation.Results The angiographic site, angiography showed lesions, the proportion of patients with coronary interventional therapy, iodixanol dosage during and preoperative and postoperative levels of SCr and eGFR and other project data between two groups were compared with no significant difference.The CIAKI incidence in observation group was 1.96% (1/51), which was significantly lower than that in control group of 16.33% (8/49) (P<0.05).The clinical follow-up after interventional treatment 30d results showed that secondary end points between two groups groups related to the project data surgery was not statistically significant.There were 2 cases with transaminases elevating, 1 case with rash and 1 case with gastrointestinal reactions, the adverse reactions rate was 7.84% (4/51) and 1 case with gastrointestinal reactions, 1 case with myalgia in control group, the adverse reactions rate was 4.08% (2/49), there was no significant difference between two groups.Conclusion This preliminary study demonstrates that rosuvastatin has the good efficacy on the DM patients with mild to moderate CKD received diuretics at high risk with security, which has the certain significance to control CIAKI.

Correlation between serum 25-hydroxyvitamin D level and gestational diabetes mellitus / 中华临床营养杂志

Objective To investigate the relationship between serum 25-hydroxyvitamin D level and gestational diabetes mellitus (GDM).Methods The fasting plasma glucose,fasting insulin,25-hydroxyvitamin D,and high sensitive C-reactive protein (hs-CRP) levels in the normal glucose tolerance group and gestational diabetes mellitus (GDM) group were measured.The homostasis model assessment insulin resistant (HOMA-IR) and homostasis model assessment β cell (HOMA-B) were calculated for assessing the insulin resistance and β-cell function.The relationship between 25-hydmxyvitamin D and hs-CRP,HOMA-IR,and HOMA-B were analyzed.Results The level of 25-hydroxyvitamin D in the GDM group [(2.16 ± 0.38) nmol/L] was significantly lower than that in the normal glucose tolerance group [(4.13 ±0.79) nmol/L](P =0.001).Serum 25-hydroxyvitamin D level was negatively correlated with hs-CRP (r =-0.448,P =0.002) and HOMA-IR (r =0.396,P =0.004),but was positively related with HOMA-B (r =0.495,P =0.001).Conclusions The serum 25-hydmxyvitamin D level remarkably decreases in GDM patients.Vitamin D deficiency may cause the functional damage of beta cell of islet,increase insulin resistance,and thus contribute to the development of GDM.

Spectral analysis and LDB based classification of heart sounds with mechanical prosthetic heart valves / 生物医学工程学杂志

Auscultation, the act of listening for heart sounds to aid in the diagnosis of various heart diseases, is a widely used efficient technique by cardiologists. Since the mechanical prosthetic heart valves are widely used today, it is important to develop a simple and efficient method to detect abnormal mechanical valves. The study on five different mechanical valves showed that only the case of perivalvular leakage could be detected by spectral estimation. Though it is possible to classify different mechanical valves by using time-frequency components of the signal directly, the recognition rate is merely 84%. However, with the improved local discriminant bases (LDB) algorithm to extract features from heart sounds, the recognition rate is 97.3%. Experimental results demonstrated that the improved LDB algorithm could improve classification rate and reduce computational complexity in comparison with original LDB algorithm.

Review of effect of Chaihu Shugan Powder on post-stroke depression / 国际中医中药杂志

The rate of stroke has been rising year by year and become the world's major cause of mortality and disability. The high rate of disability did not only bring economical burden to society and family, but also induce psychological damage to patients. Post-stroke depression (PSD) is a most common mental complications of stroke. In recent years, More and more attentions have been paid to PSD. This article reviewed the cause and mechanism of PSD and the treatment with Chaihu Shugan Powder on it.

On "Shu Shu" theory from NeiJing and modern mathematics method / 中华中医药杂志

In modern information age,the Chinese medicine scientific research is developing gradually to the direction of mathematization.Mathematics will become the middle axle,key and tool of chinese medicine multi-disciplinary research.To revive the classical medicine thoughts including "Do anything abiding by the theory of yin and yang and exercising shu shu/healthy techniques"(Suwen?Shanggu Tianzhen Lun).It is a urgent and forward-looking strategy to integrate the mathematics and the traditional Chinese medicine in the 21st century.

Comparison of cold blood and cold crystalloid cardioplegia on myocardial protection effects in valve replacement surgery / 中国医师杂志

Objective To compare the myocardial protection effects of cold blood cardioplegia and cold crystalloid cardioplegia in patients undergoing valve replacement surgery.Methods One hundred adult patients with cardiac function Ⅱ～Ⅲ class undergoing primary elective valve replacement surgery due to rheumatic heart disease were retrospectively analyzed.For patients with cardiac arrest,cold blood cardioplegia was applied to 50 cases(Group B),and cold crystalloid cardioplegia to the others(group C).The process of heart resuscitation,the postoperative need of dopamine,the blood pressure and heart rate,the postoperative level of serum myocardial enzyme,the intensive care unit(ICU) stay after operation were collected and statistically analyzed.All the cardioplegic solution was perfused in a similar manner and topical cooling was employed simultaneously.Results There were less cases in group B than in group C who needed isoprenaline for cardiac resuscitation after clamp removal(P0.05).Conclusion The cold blood cardioplegia and cold crystalloid cardioplegia have similar myocardial protection effects on rheumatic heart disease patients with cardiac function Ⅱ～Ⅲ class undergoing valve replacement surgery.

The effect of initial lower PO_2 controlled reperfusion on cyanotic hypoxic immature myocardial protection / 中华胸心血管外科杂志

Objective: To explore the effect of initial lower PO_2 controlled reperfusion on cyanotic hypoxic immature myocardium protective during post-ischemia reperfusion. Methods: 24 hypoxic neonatal rabbits were randomized into 3 groups (8 in each group). Group I (initial lower PO_2 controlled reperfusion), group II (normal PO_2 controlled reperfusion), group III (high PO_2 reperfusion group). Using isolate heart Langendorff ischemia-reperfusion model, the myocardial protection results were observed and the mechanism were discussed from molecular biological and ultrastructural view. Results: Compared with high PO_2 reperfusion group and normal PO_2 reperfusion group, the products of oxygen free radical were lowered at the end of reperfusion in initial lower PO_2 controlled reperfusion group. ATP content was increased, myocardial contractility was elevated, coronary sinus flow was raised, the degree of myocardium edema was reduced, and ultrastructure alteration was lessened significantly. Conclusion: Initial lower PO_2 controlled reperfusion reduces oxygen free radical injury, enhances myocardial energy metabolism, lessens myocytic structure destruction and improves postischemic function recovery of cyanotic myocardium.