OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

This article has systematically sorted out and verified the name， origin， producing area， quality evaluation， harvesting and processing of Pruni Semen by consulting ancient materia medica， medical books， prescription books and modern literature， in order to provide a basis for the development of famous classical formulas containing Pruni Semen. The results showed that Pruni Semen， as a medicinal material， has been widely used in medical literature of past dynasties since it was collected in Shennong Bencaojing， and also included under the names such as Yuhe， Yuzi and Yuli， and aliases such as Jueli， Queli and Chexiali. The primordial plants mentioned in the past dynasties involve about 12 species of Rosaceae， but with Prunus humilis， P. japonica and P. glandulosa as mainstream varieties used in the past dynasties， while the 2020 edition of Chinese Pharmacopoeia stipulates that the basal plants are P. humilis， P. japonica and P. pedunculata. Most of the ancient records for the origin of Pruni Semen are found everywhere in high mountains， valleys and hills， modern literature records that its origin varies according to its base， for example， P. humilis and P. japonica are mainly produced in Hebei， eastern Inner Mongolia， Liaoning， Shandong and other regions of China， and P. pedunculata is mainly produced in Inner Mongolia. Modern literature summarizes its quality as faint yellow， full and fulfilling， neat and not broken， and non-oiling， and the small Pruni Semen is better than the big Pruni Semen. The ancient processing methods of Pruni Semen mainly include blanching and peeling， blanching and peeling followed by frying， and blanching and peeling followed by pounding， with the common feature of blanching and peeling. The successive editions of Chinese Pharmacopoeia stipulate that it should be pounded when used. Based on the results of the herbal textual research and the writing time of Bianzhenglu， and combined with the market survey of Pruni Semen， it is suggested that P. humilis or P. japonica should be used as the origin of Pruni Semen in Sanpiantang， and it is harvested when the fruits are ripe， the kernels are collected by removing the stones， and processed by blanching， peeling and pounding consulting the decoction method in the current edition of Chinese Pharmacopoeia.

Objective    To summarize the experience of treating adult recurrent pectus excavatum without plate turnover. Methods    Twenty-seven patients with recurrent pectus excavatum treated by thoracoscopy-assisted placement without plate turnover from 2010 to 2019 in our hospital were enrolled. There were 23 males and 4 females with the age of 3-29 (12.81±7.79) years at the first operation, and 18-29 (21.74±3.56) years at this operation. Incision of 2-3 cm at bilateral axillary midline of the deepest point of pectus excavatum was made, and an auxiliary incision under xiphoid process was adopted according to the intraoperative situation. Results    All patients underwent thoracoscopy-assisted correction of pectus excavatum without bar turnover, and subxiphoid incision was performed in 11 patients. Twenty-five patients had one bar placed, and two patients required two bars. The operation time was 28-45 (33.00±6.44) min. Postoperative Haller index (2.95±0.40) was improved compared with preoperation (4.63±1.03). The postoperative hospital stay was 4-6 (4.00±0.32) day. All patients were followed up for 1-8 years. Complications included poor wound healing in 1 patient, and steel wire fracture and displacement in 1 patient. There was no plate rotation or bar displacement. Fourteen patients removed the bar 29-84 (40.36±13.93) months after the placement. Haller index was improved to 2.43-3.61 (2.86±0.35) during removal of steel plate. Untill June 2020, there was no recurrence of pectus excavatum. Conclusion    The treatment of adult recurrent pectus excavatum without plate turnover is satisfactory, and the protection of intercostal muscle and firm fixation is the key to ensure the success of operation and long-term effects.

Objective To introduce the application experience of a new steel bar used in minimally invasive surgery for pectus carinatum.Methods From January to October 2018, Cardiothoracic Surgery Department of Shanghai Xinhua Hospital performed a minimally invasive surgery for 25 cases of patients with pectus carinatum used a new type of steel bar.All 25 pa-tients were male, aged 10 -17 years, with an average age of(13.80 ±1.66)years.The application experience of the new bar in pectus carinatum minimally invasive surgery was summarized .Results All operations were successfully completed .The op-eration time was 35-100 min, averaged(73.44 ±17.49)min, postoperative hospital stay was 3 -6 days, averaged(3.68 ± 0.85)days.Postoperative complications included 5 cases of pneumothorax(the lung compression was about 2％ -10％, not necessary for surgical intervention).One case occured wound healing delay 1 month after operation, and healed after no surger-cal treatment.The other patients recovered smoothly.Conclusion The new steel bar is convenient to use, greatly reduces the difficulty of the pectus carinatum surgery procedure , also reduced surgical trauma and complications , has a good application prospect.

Objective:The significant role of long non-coding RNAs (lncRNAs) in early diagnosis and predicting prognosis has been recognized in various cancers recently.However,the prognostic value of HOXA transcript at the distal tip (HOTTIP),a vital lncRNA in tumorigenesis,remains unclear.In this study,we evaluated its prognostic value by analyzing the correlation of HOTTIP expression with overall survival (OS),lymph node metastasis (LNM) and distant metastasis (DM) in different cancer types by meta-analysis.Methods:We performed a systematic search in PUBMED,MEDLINE,Web of Science and Cochrane Library update to November of 2016.A total of 604 patients from 6 studies were included in final analysis and went through a quantitative meta-analysis by Review manager 5.3.Results:We demonstrated that high expression of HOTTIP had a significant correlation with poor OS (hazard ratio [HR] =2.37,95％ confidence interval [CI] =1.81-3.10,p＜0.001),high LNM rate (odds ratio [OR]=2.29,95％CI=1.54-3.40,p＜0.001) as well as more DM occurrence (OR=3.30,95％CI=1.78-6.12,p＜0.001).Conclusion:Our results indicated that long non-coding RNA HOTTIP may serve as a potential prognostic biomarker in cancer progression.

Objective To clarify the source of infection of a student brucellosis case in Ningde City, make clear its influencing range as well as risk factors of transmission, then take measures to effectively control the epidemic.Methods Clue sampling was carried out, then the survey site village was chosen where the student case came from.①Fundamental state survey: resident population as well as the situation of livestock were collected.②Human outbreak investigation: detailed interview was carried out on the first case.Base on the principle of informed consent, serum samples were collected from breeders and those who had once contacted with sheep in order to detect brucellosis antibodies, then investigation was conducted on farmers to collect cognitive information;case searching was conducted by reviewing outpatient and inpatient records as well as government broadcasting.③Livestock epidemic: serum samples from some of the sheep were collected by agricultural sector.Results There were 200 households with 500 inhabitants in the survey site of Ningde City, among which there were 5 sheep feeding families and totally 154 sheep on hand.Patient was male, 12 years old, student.Sick on June 2nd, 2014,confirmed on July 5th.The patient's neighbor was a sheep farmer, he had once contacted with the sheep.Totally we collected 8 serum samples from livestock personnel, positive Brucella antibody was 4, with a positive rate 50％ (4/8);collected 15 serum samples from those contacted with sheep, positive Brucella antibody was 2, with a positive rate 13％ (2/15).Meanwhile, agricultural sector collected 17 sheep serum samples from these two sheep farms, among which there were 7 serum samples showing a positive Brucella antibodies, with a positive rate 41％ (7/17).After surveyed of 8 livestock breeding personnel and 15 livestock non-breeding personnel, we found that no one was familiar with the clinical characteristics and transmission of brucellosis.Conclusions The direct source of brucellosis infection is local infected sheep, general population has been involved in this epidemic.Brucellosis surveillance should be seriously carried out on both human and animal.Furthermore, improving the awareness of brucellosis among professionals as well as general population is eagerly needed and health education must be carried out immediately.

Objective:To study clinical diagnostic value combined detecting plasma cardiac troponin T (cTnT)and N terminal pro B type natriuretic peptide (NT-proBNP)in children With heart failure (HF).Methods:A total of 73 child HF patients from our hospital Were enrolled as HF group,and another 75 healthy children from Well child clin-ic Were regarded as healthy control group.Concentrations of cTnT and NT-proBNP,and left ventricular ejection fraction (LVEF)Were measured and compared betWeen tWo groups.Receiver operator characteristic curve (ROC) Was used to analyze diagnostic sensitivity and specificity combined detecting cTnT and NT-proBNP.Results:Com-pared With healthy control group,there Were significant increase in concentrations of NT-proBNP [(2486.7±87.5)pmol/L vs.(3573.8±98.2)pmol/L]and cTnT [(0.03±0.01)ng/ml vs.(0.35±0.09)ng/ml],and significant decrease in LVEF [(70.8±5.2)% vs.(42.6±3.8)%]in HF group,P <0.05 all;multivariate Logistic regression analysis indicated that NT-proBNP Was an independent relative factor for LVEF in HF children (OR=1.006,P = 0.012);When NT-proBNP value Was 3200 pmol/L and cTnT value Was 0.08 ng/ml,their sensitivity and specificity Were 89.5% and 85.7% respectively in combined diagnozing child HF,and the area under ROCWas 0.795.Conclusion: Combined detecting cardiac troponin T and N terminal pro B type natriuretic peptide possesses high clinical diagnostic value in children With heart failure.

Beijing has been one of the epicenters attacked most severely by the SARS-CoV (severe acute respiratory syndrome-associated coronavirus) since the first patient was diagnosed in one of the city's hospitals. We now report complete genome sequences of the BJ Group, including four isolates (Isolates BJ01, BJ02, BJ03, and BJ04) of the SARS-CoV. It is remarkable that all members of the BJ Group share a common haplotype, consisting of seven loci that differentiate the group from other isolates published to date. Among 42 substitutions uniquely identified from the BJ group, 32 are non-synonymous changes at the amino acid level. Rooted phylogenetic trees, proposed on the basis of haplotypes and other sequence variations of SARS-CoV isolates from Canada, USA, Singapore, and China, gave rise to different paradigms but positioned the BJ Group, together with the newly discovered GD01 (GD-Ins29) in the same clade, followed by the H-U Group (from Hong Kong to USA) and the H-T Group (from Hong Kong to Toronto), leaving the SP Group (Singapore) more distant. This result appears to suggest a possible transmission path from Guangdong to Beijing/Hong Kong, then to other countries and regions.
Genome, Viral ; Haplotypes ; Humans ; Mutation ; Open Reading Frames ; Phylogeny ; SARS Virus ; genetics