Background Chronic intermittent hypobaric hypoxia (CIHH) can effectively alleviate type 2 diabetes mellitus (T2DM). In this process, the underlying mechanism in its association with the epigenetic regulation of DNA methylation in the promoter regions of glucose metabolism key enzyme genes remains unclear yet. Objective To investigate the effects of CIHH on expression and promoter region methylation of key enzyme genes related to glucose metabolism in diabetes mice, and to explore the underlying mechanism by which CIHH regulates glucose metabolism. Methods Forty C57BL/6J male mice were divided randomly into a normobaric normoxic control (NN/CON) group, a chronic intermittent hypobaric hypoxia intervention control (CIHH/CON) group, a normobaric normoxic diabetic model (NN/DM) group, and a chronic intermittent hypobaric hypoxia intervention diabetic model (CIHH/DM) group. The mice in the NN/DM and the CIHH/DM groups were fed for 7 weeks with high-fat and high-sugar diet. Subsequently, these mice were intraperitoneally injected consecutively with 50 mmol·L⁻¹ streptozotocin (STZ) for 5 d at a dose of 40 mg·kg⁻¹ (body weight) per day to create T2DM model mice. The mice in the CIHH/DM and the CIHH/CON groups were intervened by simulating hypobaric hypoxia at 5000 m altitude for 6 h per day, while the mice in the NN/DM and the NN/CON groups were always placed in a normobaric normoxic environment. All mice were continuously treated for 4 weeks, and blood glucose were monitored during this period. After the CIHH intervention experiment, the glucose tolerance and insulin sensitivity of mice were evaluated. A set of indicators involved in key glycolytic enzymes glucokinase (GK) and pyruvate kinase (PK), as well as key gluconeogenic enzymes phosphoenolpyruvate carboxyl kinase (PEPCK) and glucose-6-phosphatase (G6P) were measured in the liver of mice, including enzyme activity, relative mRNA expression level, and DNA methylation level in the gene promoter regions. Results Compared with the mice in the NN/DM group, the blood glucose levels of the mice in the CIHH/DM group decreased after the 25^th day of the CIHH intervention (P<0.05). Regarding the diabetic glucose tolerance curves, the area under the curve (AUC) of the mice in the CIHH/DM group was lower than that of the NN/DM group (P<0.05). Compared with the mice in the NN/DM group, the mice in the CIHH/DM group showed that the serum insulin content and HOMA of insulin resistance index (HOMA-IRI) decreased (P<0.05), the enzyme activities of GK and PK increased and the relative mRNA expression levels of their genes were up-regulated (P<0.05), while the enzyme activities of PEPCK and G6P decreased and the relative mRNA expression levels of their genes were down-regulated (P<0.05) in liver. The average DNA methylation levels in the promoter regions of GK, PK, PEPCK, and G6P genes in liver of mice in each group were not significantly different (P>0.05), and their correlations with mRNA expression levels were also not statistically significant (P>0.05). Conclusion CIHH intervention may reduce blood glucose level, improve glucose tolerance, alleviate insulin resistance, and regulate the key enzyme activities of glucose metabolism and the relative mRNA expression of their corresponding genes in T2DM mice, but the above phenomena are not related to the DNA methylation levels in the promoter regions of these key enzymes.

Objective To study the effects of different extracorporeal circulation temperature combined with dexmedetomidine on oxidative stress in patients undergoing cardiac surgery under cardiopulmonary bypass.Methods 240 patients who underwent cardiac surgery under cardiopulmonary bypass were selected from June 2021 to June 2024.The patients were 50 to 75 years old and did not have severe hepatic or renal insufficiency.The Mini-Mental State Examination was completed 1 day before the operation.Patients were routinely established for cardiopulmonary bypass.Patients were randomly divided into four groups(n=55):hypothermia+normal saline group(L0),hypothermia+dexmedetomidine group(L1),hyperthermia+normal saline group(H0)and hyper-thermia+dexmedetomidine group(H1).The nasopharyngeal temperature was maintained at(30±1)℃in the hypothermia group and(33±1)℃in the high-temperature group during the reflux period.Dexmedetomidine injection was intravenously injected at 1 μg/kg 10 minutes before anesthesia in L1 and H1 groups,and pumped continuously at a rate of 0.5 μg/(kg·h)until the end of surgery.L0 and H0 groups were given equal volume of normal saline until the end of operation.5 mL of central venous blood was collected before the beginning of anesthesia(T1),at the end of surgery(T2),24 h(T3)and 48 h(T4)after surgery,and serum neuron specific enolase(NSE),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels were detected by ELISA.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in serum were determined by xanthine oxidase method and thiobarbituric acid method.The Confusion Assessment Method-ICU was used to evaluate the occurrence of POD.Results 220 patients were finally enrolled,including 81 patients in POD group,with an incidence of 36.8%.Compared with NPOD group,the concentrations of NSE,IL-6,TNF-ɑ and MDA in POD group were in-creased,while the concentration of SOD was decreased.Compared with L0 group,the concentrations of NSE,IL-6,TNF-ɑ and MDA were decreased and the concentration of SOD increased in L1 group.Compared with H0 group,NSE,IL-6,TNF-ɑ and MDA concentrations in H1 group were decreased,while SOD concentration was in-creased.Compared with L0 group,concentration of NSE,IL-6,TNF-ɑ and MDA increased,while the concentra-tion of SOD decreased in H0 group.Compared with L1 group,concentration of NSE,IL-6,TNF-ɑ and MDA in-creased,while the concentration of SOD decreased in H1 group.Conclusion Hypothermia combined with dexme-detomidine during cardiopulmonary bypass can reduce oxidative stress response and POD in patients.

Objective To study the effects of different extracorporeal circulation temperature combined with dexmedetomidine on oxidative stress in patients undergoing cardiac surgery under cardiopulmonary bypass.Methods 240 patients who underwent cardiac surgery under cardiopulmonary bypass were selected from June 2021 to June 2024.The patients were 50 to 75 years old and did not have severe hepatic or renal insufficiency.The Mini-Mental State Examination was completed 1 day before the operation.Patients were routinely established for cardiopulmonary bypass.Patients were randomly divided into four groups(n=55):hypothermia+normal saline group(L0),hypothermia+dexmedetomidine group(L1),hyperthermia+normal saline group(H0)and hyper-thermia+dexmedetomidine group(H1).The nasopharyngeal temperature was maintained at(30±1)℃in the hypothermia group and(33±1)℃in the high-temperature group during the reflux period.Dexmedetomidine injection was intravenously injected at 1 μg/kg 10 minutes before anesthesia in L1 and H1 groups,and pumped continuously at a rate of 0.5 μg/(kg·h)until the end of surgery.L0 and H0 groups were given equal volume of normal saline until the end of operation.5 mL of central venous blood was collected before the beginning of anesthesia(T1),at the end of surgery(T2),24 h(T3)and 48 h(T4)after surgery,and serum neuron specific enolase(NSE),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels were detected by ELISA.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in serum were determined by xanthine oxidase method and thiobarbituric acid method.The Confusion Assessment Method-ICU was used to evaluate the occurrence of POD.Results 220 patients were finally enrolled,including 81 patients in POD group,with an incidence of 36.8%.Compared with NPOD group,the concentrations of NSE,IL-6,TNF-ɑ and MDA in POD group were in-creased,while the concentration of SOD was decreased.Compared with L0 group,the concentrations of NSE,IL-6,TNF-ɑ and MDA were decreased and the concentration of SOD increased in L1 group.Compared with H0 group,NSE,IL-6,TNF-ɑ and MDA concentrations in H1 group were decreased,while SOD concentration was in-creased.Compared with L0 group,concentration of NSE,IL-6,TNF-ɑ and MDA increased,while the concentra-tion of SOD decreased in H0 group.Compared with L1 group,concentration of NSE,IL-6,TNF-ɑ and MDA in-creased,while the concentration of SOD decreased in H1 group.Conclusion Hypothermia combined with dexme-detomidine during cardiopulmonary bypass can reduce oxidative stress response and POD in patients.

ObjectiveTo evaluate the clinical safety of Naoxintong （NXT） capsules after marketing， find out the potential risk factors of the drug as soon as possible， and reveal the incidence， nature， and clinical manifestations of the adverse events （ADE） and adverse reactions （ADR） of NXT capsules， so as to provide a basis for safe use of the drug in clinical practice. MethodA prospective， large-sample， multi-center observational cohort study was conducted to monitor all the 7 345 inpatients and outpatients orally taking NXT in 14 hospitals in China from January to December in 2018， with at least one follow-up. The demographic characteristics， disease type， NXT medication， ADR occurrence， characteristics， and prognosis of the patients were collected. SPSS 23.0 was used for single-factor and multivariate logistic regression to predict the influencing factors of ADR. ResultThe male and female patients accounted for similar proportions. There were 5 081 patients （79.40%） aged ≥60 years and 3 153 patients （49.27%） with body mass index （BMI） exceeding the normal standard. There were 344 （5.38%） patients with a history of allergy to medicines and food， 9 （0.14%） patients with a family history of allergy， and 52 （0.81%） patients with a history of allergic diseases. The ADRs associated with NXT occurred in 22 patients， with the incidence of 0.34%. The clinical manifestations of ADR appeared in 31 cases， involving 10 organs/systems， of which gastrointestinal system damage was the most common （17， 54.84%）. All ADRs were mild or moderate. Most ADRs （19， 86.36%） occurred within 4 weeks after administration. The patients with alleviated NXT-associated ADRs accounted for 81.82%. No indicators related to significant increases in ADR risks were found. ConclusionNXT is well tolerated in the general population. The hospital centralized monitoring for the clinical safety of oral Chinese patent drugs based on HIS data and Web tracking and follow-up system is an essential means for the post-market research on the safety of drugs.

Gastric cancer is a common malignant tumor of digestive tract in China. Precise, minimally invasive and standardized surgical operation is an important part of comprehensive treatment for gastric cancer. In recent years, indications for minimally invasive surgery have been expanding, research on precision surgery has been deepening, and the standardized surgical quality evaluation and control system has been improving. Accurate diagnosis and staging, multi-disciplinary comprehensive diagnosis and treatment model, enhanced recovery after surgery and whole-process management of nutrition support and other aspects have been comprehensively developed. A number of Chinese expert consensus has been issued, which is conducive to the rapid and good recovery of patients, achieving the double benefits of improving the quality of life and prolongation of survival. However, the precise treatment of complex conditions is still full of controversy. This consensus is formulated to facilitate the standardization of the diagnosis and treatment of gastric cancer.

Gastric cancer is a common malignant tumor of digestive tract in China. Precise, minimally invasive and standardized surgical operation is an important part of comprehensive treatment for gastric cancer. In recent years, indications for minimally invasive surgery have been expanding, research on precision surgery has been deepening, and the standardized surgical quality evaluation and control system has been improving. Accurate diagnosis and staging, multi-disciplinary comprehensive diagnosis and treatment model, enhanced recovery after surgery and whole-process management of nutrition support and other aspects have been comprehensively developed. A number of Chinese expert consensus has been issued, which is conducive to the rapid and good recovery of patients, achieving the double benefits of improving the quality of life and prolongation of survival. However, the precise treatment of complex conditions is still full of controversy. This consensus is formulated to facilitate the standardization of the diagnosis and treatment of gastric cancer.

This study was aimed to analyze four diagnostic methods of AIDS patients with HAART complicated with anemia and hyperlipidemia. Characteristics of traditional Chinese medicine (TCM) and common pathogenesis were discussed in this article. This study was supported by Key Project of the National Eleventh-Five Year Research Program of China. This study was conducted through the retrospective analysis. This analysis was made on the four diagnostic methods of AIDS patients with HAART treatment. The results showed that the most frequent symptoms of AIDS patients with anemia or hyperlipidemia are fatigue, facial abnormalities, taste abnormalities, forgetfulness, backache, weakness of back, loss of appetite, insomnia. And the frequent tongue and pulse are white tough coating, pale tongue and fine pulse. The most frequent symptoms of the anemia group are facial abnormalities, backache, dizziness, palpitations, shortness of breath, pale complexion, abnormal state of mind, abnormal sweating, tinnitus, cold hands and feet, spontaneous sweating, white tongue coating, tooth-printed tongue, thin tongue coating and weak pulse (P < 0.05). The most frequent symptom of hyperlipidemia are lassitude, weakness, loss of appetite, abdominal distension, moisture tongue, thick and greasy tongue coating, slippery pulse. It was concluded that syndromes of AIDS patients on ARV complicated with anemia and hyperlipidemia are mainly deficient pattern, which affects the spleen, heart, liver and kidney. The most frequent syndrome type with anemia patients is blood deficiency, which is followed by spleen-kidney deficiency syndrome, liver-kidney deficiency syndrome. The most frequent syndrome type with hyperlipidemia patients is spleen qi deficiency and kidney essence deficiency, which are closely related to the spleen and kidney.

ObjectiveTo study the pharmacokinetics of sufentanil in patients undergoing different cardiac surgeries with or without CPB.MethodsSixteen ASA Ⅱ or Ⅲ patients aged 56-64 yr weighing 52-78 kg undergoing cardiac surgery were divided into 2 groups ( n ＝ 8 each):group Ⅰ off-pump coronary artery bypass grafting and group Ⅱ valve replacement.Radial artery and peripheral vein were cannnlated.A bolus of sufentanil 5μg/kg was administered iv after induction of anesthesia.Blood samples were obtained from radial artery at 1,3,5,10,20,30,60,120,180,240,360 min after sufentanil injection.Plasma was immediately separated and stored at - 80 C for determination of plasma sufentanil concentration by liquid c hromatography-mass spectrometry.Pharmacokinetic parameters were calculated by 3P97 pharmacological program.ResultsThe pharmacokinetic profile of sufentanil was best described by a three-compartment open model.The 3 exponential equations in group Ⅰ,before and during CPB in group Ⅱ were:Cp(t) ＝ 11.7 e-0.47t + 1.9 e0.043t + 0.27 e-0.0032t ; Cp(t) ＝ 33.4 e-1.87t + 7.1e-0.103t +2.0 e-0.0248t and Cp(t) ＝ 23.8 e-0.54t + 5.2 e0.054t + 0.15 e-0.0017t respectively.There was significant difference in most of the pharmacokinetic parameters between the 2 groups.ConclusionsThe pharmacokinetics of sufentanil in patients undergoing different cardiac surgeries can be described by ~compartment open model.Low cardiac function and CPB can reduce its drug metabolism rate and prolong the duration of action.

To study the characteristics of traditional Chinese medicine (TCM) syndrome factors of patients from different areas of China with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).

Objective To assess the effect of different ages on sufentanil pharmacokinetics in patients undergoing cardiac valve replacement.Methods Sixteen NYHA Ⅱ or Ⅲ patients undergoing selective cardiac valve replacement were randomly divided into two groups:elderly group (aged 65-69 years,group Ⅰ,n =8) and young adult group (aged 36-45 years,group Ⅱ,n =8).Intravenous and intra-arterial cannulae were placed.Sufentanil 5 μg/kg injected intravenously during anesthesia induction.Blood samples from the radial artery were obtained at 1,3,5,10,20,30,60,120,180,240 and 360 min after sufentanil injection (3 ml each).Then 1 ml plasma was immediately separated from the 3 ml blood sample and stored at - 80 ℃ until being assayed.Plasma sufentanil concentration was determined with liquid chromatography mass spectrometry and pharmacokinetic parameters were calculated with 3P97 pharmacologicl program.Results Plasma sufentanil concentration versus the time decay curve in patients undergoing cardiac valve replacement before cardiopulmonary bypass (CPB) was fitted to a twocompartment model and could be expressed by bi-exponential equations:Cp (t) =27.4 e-0.41t + 3.2 e-0.029t in group Ⅰ and Cp (t) =14.4 e-0.51t +3.4 e-0.032t in group Ⅱ,respectively.There were significant differences in t 1/2 α,t1/2 β and CL between the two groups ( P ＜ 0.05 or 0.0l ).During CPB,plasma sufentanil concentration versus the time decay curve in patients undergoing cardiac valve replacement was fitted to a three-compartment model and could be expressed by tri-exponential equations:Cp(t) =22 e-0.51t + 3.5 e-0.045t + 0.21 e-0.0029 t in group Ⅰand Cp(t) =15 e-0.52t + 3.9 e-0.048t + 0.32 e-0.004t in group Ⅱ,respectively.There were no significant differences in pharmacokinetic parameters between the two groups ( P ＞ 0.05).Conclusion There are significant differences in sufentanil phannacokinetic characteristics before CPB but different ages have no obvious influence on sufentanil pharmaco-kinetics during CPB.