BACKGROUND:Increased homocysteine level induces apoptosis of human umbilical vein endothelial cells,but the mechanism remains unclear. OBJECTIVE:To investigate the role of hsa-circ-0001360 in human umbilical vein endothelial cell apoptosis induced by homocysteine. METHODS:In vitro cultured human umbilical vein endothelial cells were divided into control group,homocysteine group,interference control group,interference control + homocysteine group,hsa-circ-0001360 interference group,hsa-circ-0001360 + homocysteine interference group,overexpression control group,overexpression control + homocysteine group,hsa-circ-0001360 overexpression group and hsa-circ-0001360 + homocysteine overexpression group.All groups were treated with 100 μmol/L homocysteine.After 72 hours of intervention,the expressions of apoptosis-related proteins Bax,Bcl-2,and Caspase-3 were detected by western blot assay.The apoptotic rate was detected by flow cytometry.Quantitative real-time PCR was used to detect the expression of hsa-circ-0001360. RESULTS AND CONCLUSION:(1)Compared with the control group,the expression of Caspase-3 and Bax was significantly increased(P<0.01),and the expression of Bcl-2 was significantly decreased(P<0.01),and the apoptotic rate was significantly increased(P<0.01)in the homocysteine group.(2)Compared with control group,the expression of hsa-circ-0001360 was significantly increased in the homocysteine group(P<0.01).(3)The expression of hsa-circ-0001360 was significantly higher in the cytoplasm than that in the nucleus(P<0.01).(4)Compared with the interference control C group and interference control + homocysteine group,the expressions of Caspase-3 and Bax were significantly decreased(P<0.01),while the expression of Bcl-2 was significantly increased(P<0.01);the apoptotic rate was significantly decreased(P<0.01)in sh-hsa-circ-0001360 interference group and sh-hsa-circ-0001360 + homocysteine interference group.(5)Compared with overexpression control group and overexpression control + homocysteine group,the expressions of Caspase-3 and Bax were significantly increased(P<0.01),while the expression of Bcl-2 was significantly decreased(P<0.01);the apoptotic rate was significantly increased(P<0.01)in the hsa-circ-0001360 overexpression group and the hsa-circ-0001360 + homocysteine overexpression group.(6)In conclusion,hsa-circ-0001360 can promote the apoptosis of human umbilical vein endothelial cells induced by homocysteine.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

Objective:To compare the efficacy of closed-loop target-controlled deep versus moderate neuromuscular blockade in gynecological laparoscopic surgery.Methods:This was a prospective study. Fifty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective gynecological laparoscopic surgery in the General Hospital of Tianjin Medical University from March 2020 to March 2021, were allocated into 2 groups ( n=25 each) using a random number table method: closed-loop target-controlled moderate neuromuscular blockade group (group TOF) and closed-loop target-controlled deep neuromuscular blockade group (group PTC). Rocuronium was given by closed-loop target-controlled infusion in both groups. In group TOF, the target muscle relaxation was considered as train-of-four stimulation (TOF) of 1 or 2. In group PTC, the target muscle relaxation was considered as post-titanic count of 1 or 2. The score for operator′s satisfaction with muscle relaxation, grading, satisfaction rate, mean pneumo-peritoneum pressure, consumption of rocuronium, recovery index, recovery time to a TOF ratio 0.9 and time to extubation were recorded. The postoperative visual analogue scale score for abdominal pain and use of rescue analgesics were recorded, and the occurrence of complications such as shoulder pain, arm pain, nausea, vomiting and hypoxemia was also recorded within 48 h after surgery. Results:Compared with group TOF, the score for operator′s satisfaction with muscle relaxation, grading and satisfaction rate were significantly increased, the mean pneumo-peritoneum pressure was decreased, the total and average consumption of rocuronium was increased, the recovery time of a TOF ratio 0.9 was prolonged, and the postoperative visual analogue scale score for abdominal pain and usage rate of flurbiprofenate were decreased in group PTC ( P<0.05). There were no significant differences in the recovery index, tracheal extubation time or postoperative incidence of hypoxemia, shoulder pain, arm pain and nausea and vomiting between the two groups ( P>0.05). Conclusions:Compared with the closed-loop target-controlled moderate neuromuscular blockade, the closed-loop target-controlled deep neuromuscular blockade provides more satisfactory surgical conditions for gynecological laparoscopic surgery, decreases pneumoperitoneum pressure and reduces related complications, without increasing the development of postoperative adverse reactions.

Objective:To investigate the role of survivin in the regulation of leptin expression and its sensitivity.Methods:Survivin was overexpressed in adipocytes via lentivirus, and the RNA-sequencing(RNA-seq) was used to explore the effect of survivin on the regulation of adipocyte secretory proteins. Survivin was overexpressed in the inguinal adipose tissue(iWAT) of mice by targeted injection of adeno-associated virus(AAV). The transcription levels of leptin and adiponectin were detected by realtime quantitative PCR(RT-qPCR), and the secretion levels of leptin and adiponectin in cellular supernatants and mice serum were detected by enzyme-linked immunosorbent assay(ELISA). The protein level of phosphorylated signal transducer and activator of transcription 3(STAT3) in hypothalamus was detected by Western blotting to investigate the effect of survivin on central leptin sensitivity.Results:Survivin overexpression in both 3T3-L1 and primary white adipocyte significantly down-regulated the leptin transcriptional expression without affecting the adipocyte differentiation( P<0.01). Overexpression of survivin significantly decreased leptin level without affecting the adiponectin levels in the cellular supernatant( P<0.001). Overexpression of survivin in iWAT via AAV injection, not only specifically down-regulated leptin transcriptional level in a dose dependent manner in local adipose tissue, but also led to a decrease in serum leptin level( P<0.05). In mice fed short-term high-fat diet, STAT3 phosphorylation level in hypothalamus significantly increased, suggesting improved central leptin sensitivity. Conclusion:Survivin could downregulate leptin expression and improve leptin sensitivity in high-fat diet induced obese mice.

Objective To investigate the value of serum markers in the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE). Methods A prospective analysis was performed for 81 patients who were hospitalized and treated in General Hospital of Ningxia Medical University from April 2020 to February 2022, and all these patients were diagnosed with hepatitis B cirrhosis based on clinical manifestation, laboratory examination, and radiological examination or liver biopsy. According to digital connection test A (NCT-A) and digital symbol test (DST), these patients were divided into simple cirrhosis group with 45 patients and MHE group with 36 patients. Related indices were measured, including liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBil)], albumin, blood ammonia, cholinesterase, and prothrombin time. The independent samples t -test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The logistic regression analysis and the area under the ROC curve (AUC) were used to investigate the predictive factors for MHE. Results Compared with the simple cirrhosis group, the MHE group had a significant increase in NCT-A score ( Z =-7.110, P < 0.001) and a significant reduction in DST score ( t =12.223, P < 0.001). The univariate analysis showed that there were significant changes in AST, albumin, prothrombin time, cholinesterase, and blood ammonia in the patients with MHE ( Z =-2.319, -2.643, -1.982, -6.594, and -5.331, all P < 0.05), while the multivariate analysis showed that only cholinesterase and blood ammonia were significant predictive factors (all P < 0.05) and were correlated with Child-Pugh score (all P < 0.05). Cholinesterase, blood ammonia, and their combination had an AUC of 0.925, 0.845, and 0.941, respectively, in the diagnosis of MHE, with an optimal cut-off value of 2966, 60, and 0.513, respectively. Conclusion Blood ammonia, cholinesterase, and their combined measurement have a potential clinical value in the early diagnosis of liver cirrhosis with MHE.

Diabetes mellitus(DM),as a common and frequently-occurring disease,has become a huge burden of chronic diseases worldwide,whose pathogenesis is very complex and has not yet been fully elucidated.Small intestine is one of important immune organ in body,and relationship between its innate immune function and DM has become forefront of research in medical field.In this paper,role of intestinal innate immunity in pathogenesis of DM is reviewed,including tissue barrier dysfunction of small intestine,dysfunction of intestinal innate immune cells and imbalance of proportion of intestinal innate immune molecules,in order to provide references for future research on related mechanisms.

OBJECTIVE To study the in vitro transdermal characteristics of Tibetan new drugs hereinafter referred to as Zhengrutie cataplasm, and to evaluate the safety of skin medication by using different species of animals(guinea pigs, New Zealand rabbits). METHODS The improved vertical Franz diffusion cell method was used for in vitro transdermal testand the skin of Bama miniature pig was used as the permeation barrier. The cumulative permeation amount and rate of geniposide methyl ester and 8-O-acetyl geniposide methyl ester, borneol and camphor in the receiving medium were determined by HPLC and GC, respectively, to investigate the in vitro transdermal characteristics of Zhengrutie cataplasm. Buehler test was used to study the sensitization of Zhengrutie cataplasm on guinea pig skin. Observed the skin irritation after single or multiple application of Zhengrutie cataplasm on intact and damaged skin of New Zealand rabbits. RESULTS The cumulative permeation amount of the sum of geniposide methyl ester and 8-O-acetyl geniposide methyl ester, borneol and camphor within 24 h were 14.14, 348.21, 490.97 μg·cm-2, respectively. The cumulative permeation amount were 6.2%, 10.2% and 15.3%, respectively. The average permeation amount were 0.59, 14.51 and 20.46 μg·cm-2·h-1. No allergic reaction to guinea pig skin, no irritation to intact skin of New Zealand rabbits, mild irritation to damaged skin. CONCLUSION The in vitro transdermal performance of Zhengrutie cataplasm is good. The in vitro transdermal process conforms to the zero-order kinetic equation. It has no irritation and sensitization effect on the skin of guinea pigs and New Zealand rabbits. It is safe and reliable for skin external use and has good clinical application value.

A total of 115 patients with type 2 diabetes recruited from Quanzijie Township Health Service Center were divided into integrated management group (n=54) and specialist management group (n=61). Patients in integrated management group were managed by specialists, general practitioners (GPs) and community nurses jointly; while patients in specialist management group were managed by specialists only. Subjects were followed up every 4 weeks for 24 weeks. Total 366 person/time diabetes education courses were given to subjects in integrated management group during the intervention. After intervention, the fasting glucose, 2 h postprandial glucose and glycosylated hemoglobin were decreased significantly in both groups (P<0.05), while the triglyceride level in the integrated management group was significantly lower than that in the specialist management group (P<0.05). In conclusion, patients with type 2 diabetes managed by integrated mode can achieve similar glucose control effect as specialist management mode in primary care settings and their triglyceride level can be also significantly decreased.

Objective: To explore the effect of "diabetes specialists-community general practitioners-community nurse co-management mode" and "diabetes specialist management mode" on diabetic nephropathy (DN) in primary medical institutions. Methods: Patients with type 2 diabetes admitted to Quanzijie Health Clinic of Jimusar County of Xinjiang Uygur Autonomous Region from October 2017 to March 2018 were enrolled. The Patients were divided into co-management group or specialist management group according to their administrative villages. The treatment plans of the two groups were formulated with reference to the current guidelines. The subjects of the co-management group were jointly managed by a fixed team composed of diabetes specialists from Jimusar Traditional Chinese Medicine Hospital, community general practitioners and community nurses from Quanzijie Health Clinic, and required to attend diabetes education courses every month. The diabetes specialist of Jimusar Traditional Chinese Medicine Hospital was responsible for the formulation and management of the treatment plan of the research object. Follow-up was fulfilled once every 4 weeks for 24 weeks in two groups. Before and after intervention, blood glucose, blood pressure, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) as well as the utilization rate of angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor blocker (ACEI/ARB) were collected. Results: A total of 115 patients accomplished this study with 54 patients in co-management group and 61 patients in specialist management group. After 24 weeks of intervention, fasting glucose level, postprandial glucose level 2 hours after breakfast, glycosylated hemoglobin (HbA1c), Log UACR in co-management group and specialists management group were significantly decreased compared with baseline [fasting glucose level (mmol/L): 8.06±1.92 vs. 9.16±2.83, 8.21±2.10 vs. 9.06±1.89; postprandial glucose level 2 hours after breakfast (mmol/L): 12.26±3.78 vs. 14.11±5.28, 12.47±3.63 vs. 14.00±3.88; HbA1c: 0.074±0.014 vs. 0.082±0.023, 0.076±0.014 vs. 0.081±0.016; Log UACR (mg/g): 1.63±1.56 vs. 2.25±1.44, 1.84±1.65 vs. 2.43±1.56, all P < 0.05], but there was no statistical significance between the two groups [fasting glucose level (mmol/L): -1.10±0.47 vs. -0.85±0.36, postprandial glucose level 2 hours after breakfast (mmol/L): -1.85±0.88 vs. -1.53±0.68, HbA1c: -0.008±0.004 vs. -0.006±0.003, Log UACR (mg/g): -0.61±0.29 vs. -0.59±0.29, all P < 0.05]. There were no significant changes in blood pressure, serum creatinine and eGFR in the two groups before and after intervention. There were 18 and 24 patients with hypertension in co-management group and specialist management group, respectively. The utilization rates of ACEI/ARB in both groups after intervention were significantly higher than those before intervention [88.9% (16/18) vs. 22.2% (4/18), 95.8% (23/24) vs. 29.2% (7/24), both P < 0.01]. At the end of the study, the utilization rate of ACEI/ARB was similar between the two groups [88.9% (16/18) vs. 95.8% (23/24), P > 0.05]. Conclusion Both "diabetes specialists-community general practitioners-community nurse co-management mode" and "diabetes specialist management mode" can effectively decrease glucose levels and UACR levels of patients with type 2 diabetes as well as the standard use of antihypertensive agents, which has positive effects on the prevention and treatment on DN.

OBJECTIVE: To explore the effect of "diabetes specialists-community general practitioners-community nurse co-management mode" and "diabetes specialist management mode" on diabetic nephropathy (DN) in primary medical institutions. METHODS: Patients with type 2 diabetes admitted to Quanzijie Health Clinic of Jimusar County of Xinjiang Uygur Autonomous Region from October 2017 to March 2018 were enrolled. The Patients were divided into co-management group or specialist management group according to their administrative villages. The treatment plans of the two groups were formulated with reference to the current guidelines. The subjects of the co-management group were jointly managed by a fixed team composed of diabetes specialists from Jimusar Traditional Chinese Medicine Hospital, community general practitioners and community nurses from Quanzijie Health Clinic, and required to attend diabetes education courses every month. The diabetes specialist of Jimusar Traditional Chinese Medicine Hospital was responsible for the formulation and management of the treatment plan of the research object. Follow-up was fulfilled once every 4 weeks for 24 weeks in two groups. Before and after intervention, blood glucose, blood pressure, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) as well as the utilization rate of angiotensin converting enzyme inhibitors/angiotensin II receptor blocker (ACEI/ARB) were collected. RESULTS: A total of 115 patients accomplished this study with 54 patients in co-management group and 61 patients in specialist management group. After 24 weeks of intervention, fasting glucose level, postprandial glucose level 2 hours after breakfast, glycosylated hemoglobin (HbA1c), Log UACR in co-management group and specialists management group were significantly decreased compared with baseline [fasting glucose level (mmol/L): 8.06±1.92 vs. 9.16±2.83, 8.21±2.10 vs. 9.06±1.89; postprandial glucose level 2 hours after breakfast (mmol/L): 12.26±3.78 vs. 14.11±5.28, 12.47±3.63 vs. 14.00±3.88; HbA1c: 0.074±0.014 vs. 0.082±0.023, 0.076±0.014 vs. 0.081±0.016; Log UACR (mg/g): 1.63±1.56 vs. 2.25±1.44, 1.84±1.65 vs. 2.43±1.56, all P < 0.05], but there was no statistical significance between the two groups [fasting glucose level (mmol/L): -1.10±0.47 vs. -0.85±0.36, postprandial glucose level 2 hours after breakfast (mmol/L): -1.85±0.88 vs. -1.53±0.68, HbA1c: -0.008±0.004 vs. -0.006±0.003, Log UACR (mg/g): -0.61±0.29 vs. -0.59±0.29, all P < 0.05]. There were no significant changes in blood pressure, serum creatinine and eGFR in the two groups before and after intervention. There were 18 and 24 patients with hypertension in co-management group and specialist management group, respectively. The utilization rates of ACEI/ARB in both groups after intervention were significantly higher than those before intervention [88.9% (16/18) vs. 22.2% (4/18), 95.8% (23/24) vs. 29.2% (7/24), both P < 0.01]. At the end of the study, the utilization rate of ACEI/ARB was similar between the two groups [88.9% (16/18) vs. 95.8% (23/24), P > 0.05]. CONCLUSIONS Both "diabetes specialists-community general practitioners-community nurse co-management mode" and "diabetes specialist management mode" can effectively decrease glucose levels and UACR levels of patients with type 2 diabetes as well as the standard use of antihypertensive agents, which has positive effects on the prevention and treatment on DN.
Blood Glucose ; Creatinine ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Humans ; Prospective Studies