Objective To test the accuracy of American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for preoperative cardiovascular evaluation for noncardiac surgery in Chinese patients and to compare ACC/AHA guidelines with Goldman index and Lee index. Methods From January to December 2003, all patients aged ≥70 yr or patients aged 40-69 yr with a history of cardio- and cerebro-vascular disease, abnormal ECG or diabetes scheduled for noncardiovascular surgery were included in this study. A total of 1 248 patients were eligible. Their clinical data including demographic data, history of cardiovascular disease, routine physical examination and laboratory tests, the scheduled surgery and type of anesthesia were collected. The patients were then evaluated for cardiac risk and classified according to ACC/AHA guidelines (high, moderate, low and no risk), Lee index (class I -IV ) and Goldman index (class I - III ). The cardiac risk of the scheduled surgery was then stratified according to ACC/AHA guidelines. The patients were followed up until discharged from hospital. Cardiac events were defined as cardiac death, myocardial infarct, myocardial ischemia, minor myocardial cell injury, ventricular dysfunction and serious arrhythmia. Likelihood ratio of the 3 methods was calculated. Risk factors for adverse events were identified by univariate analysis and multivariate Logistic regression analysis. Results Of the 1 248 patients 694 were male and 554 female. Their age ranged from 40-102 years (mean age 65.4 yr). 44.7 % of the patients were aged ≥ 70 years. High risk operation accounted for 6.3 % and emergency operation 7.9% . One patients died of cardiac event and ten patients of other causes. Seventy-three perioperative cardiac events occurred in 53 patients. The morbidity rate was 4.2% . Goldman index and ACC/AHA cardiac risk stratification were correlated with adverse cardiac outcomes ( P

It aimed to analyze the price disclosure system of genetic drugs in Australia.Based on the analysis of background and historical evolution,it tracked each step of price disclosure on the basis of descriptive statistics and analvsis so as to provide reterences for constructing the price disclosure system of genetic drugs led by market factor under the effective conduct of future medical reform policy in China.

Objective To compared analgesic effect of sufentanil and fentanyl in surgery patients during mechanical ventilation, and to explore the rational dosage of analgesic and sedative drugs. Methods A prospective randomized controlled trial was conducted. 600 postoperative critically ill patients underwent mechanical ventilation for 12-72 hours admitted to Department of Critical Care Medicine of the Second Affiliated Hospital of Kunming Medical University from April 2013 to March 2015 were enrolled. They were randomly divided into two groups, sufentanil and fentanyl was used for analgesia respectively, and 300 patients in each group. The initiate dosage of sufentanil and fentanil was 5 μg/h and 50 μg/h, and the dosage was adjusted. A postoperative pain score (Prince-Henry score) of 0-1, and Richmond agitation-sedation scale (RASS) score -1-0 were targeted. 1 mg/kg of propofol was used if patient could not fall in sleep or felt anxious after loading dose of sufentanil (5 μg) or fentanil (50 μg) for 5 minutes. The use of analgesic drugs, the proportion and dosage of propofol was observed in the two groups, and adverse reactions were recorded. Results The mean dose of sufentanil for analgesia was (0.07±0.02) μg·kg-1·h-1, and the mean dose of fentanyl was (0.67±0.12) μg·kg-1·h-1. The patients in the two groups received propofol 40 to 60 mg/h in night, and the use proportion of propofol in sufentanil group was slightly less than that in fentanyl group (25.7% vs. 28.3%), but the difference was not statistically significant (P > 0.05). It was found by subgroup age analysis that, the mean analgesic dose of sufentanil or fentanyl in patients over 80 years old was lower than that in 70-79 years, 60-69 years and < 60 years groups but without statistical significance. There were 11 cases (3.7%) and 21 cases (7.0%) patients suffered from respiratory depression in sufentanil group and fentanyl group, respectively, without statistical significance (P = 0.069). The hemodynamics of patients in two groups was stable during analgesia, and no accidental extubation due to restlessness was found. Conclusions A smaller dose of sufentanil for postoperative patients underwent mechanical ventilation with satisfactory analgesia was (0.07±0.02) μg·kg-1·h-1, but need to be added with 40-60 mg/h and a small dose of propofol to improve anxiety and sleep. The proportion of patients needing propofol addition was slightly lower than that of fentanyl.

Objective To evaluate the effect of OPRM1A118G genetic polymorphism on postoperative analgesia with fentanyl in the patients undergoing radical resection of lung cancer.Methods One hundred and seventy-four patients(native of He′nan province), aged 40-64 yr, weighing 40-70 kg, with American Society of Anesthesiologists physical status Ⅰor Ⅱ, undergoing elective radical resection of lung cancer under general anesthesia, were enrolled in this study.OPRM1A118G genetic polymorphic sites were analyzed by using polymerase chain reaction technique and ABI 3130 Genetic Analyzer.The patients were divided into wild homozygote group,heterozygote group and mutation homozygote group according to their genotypes.The analgesia pump was connected at the end of operation.Patient-controlled intravenous analgesia solution contained fentanyl 30 μg/kg and ondansetron 8 mg in 200 ml of normal saline.The analgesia pump was programmed to deliver a 2 ml bolus dose with a 15-min lockout interval and background infusion at a rate of 2 ml/h, maintaining the visual analogue scale score ≤3 points.The amount of fentanyl consumed within 24 and 48 h after operation was recorded, and the occurrence of adverse reactions was recorded within 48 h after operation.Results Compared with wild homozygote group, the amount of fentanyl consumed within 24 and 48 h after operation was significantly increased in mutation homozygote group(P<0.05), and no significant change was found in the amount of fentanyl consumed within 24 and 48 h after operation in heterozygote group(P>0.05).There was no significant difference in the incidence of postoperative adverse reactions between the three groups(P>0.05).Conclusion OPRM1A118G genetic polymorphism is one of the genetic factors contributing to individual variation in fentanyl pharmacodynamics in the patients undergoing radical resection of lung cancer.

Objective To evaluate the effects of OPRM1All8G and CYP3A4*18B genetic polymorphism and the interaction on postoperative analgesia with fentanyl in the patients undergoing radical resection of lung cancer.Methods One hundred and thirty-nine patients (native of Henan province),aged 40-64 yr,weighing 40-70 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective radical resection of lung cancer under general anesthesia,were enrolled in this study.The polymorphic sites of the OPRM1All8G and CYP3A4*18B allele were analyzed by using polymerase chain reaction technique and ABI 3130 Genetic Analyzer.The patients were divided into wild homozygote group (group AA,group *1/*1),heterozygote group (group AG,group * 1/*18B) and mutation homozygote group (group GG,group *18B/*1SB) according to their genotypes.The patients were divided into 7 groups according to the interaction between the two genes:AA plus *1/*1 group (group Ⅰ),AA plus *1/*18B group (group Ⅱ),AG plus *1/*1 group (group Ⅲ),AG plus *1/*18B group (group Ⅳ),GG plus * 1/*1 group (group Ⅴ),GG plus *1/*18B group (group Ⅵ) and *18B/*18B group (group Ⅶ).Patientcontrolled intravenous analgesia with fentanyl was started at the end of surgery to maintain the visual analogue scale ≤ 3 points.The amount of fentanyl used within 24 and 48 h after surgery was recorded,and the occurrence of adverse reactions within 48 h after surgery was observed.Results The amount of fentanyl used within 24 and 48 h after surgery was significantly higher in group GG than in group AA (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly lower in group *18B/*18B than in group *1/*1 (P＜0.05).The amount of fentanyl used within 48 h after surgery was significantly higher in Ⅱ and Ⅳ groups than in group Ⅰ,in group Ⅲ than in group Ⅱ,in group Ⅴ than in Ⅰ-Ⅳ groups,and in group Ⅵ than in Ⅱ and Ⅳ groups,and was significantly lower in group Ⅶ than in Ⅰ-Ⅵ groups (P＜ 0.05).There was no significant difference in the incidence of adverse reactions within 48 h after surgery between groups (P＞0.05).Conclusion OPRM1A1l8G and CYP3A4*18B genetic polymorphism and the interaction are the genetic factors contributing to individual variation in fentanyl pharmacodynamics in the patients undergoing radical resection of lung cancer.

Objective:To analyze the clinical characteristics and outcomes of critically ill pregnant and parturient women in intensive care unit (ICU), and to provide clinical experience for the subspecialty construction of critical obstetrics.Methods:The clinical data of critically ill pregnant and parturient women admitted to the department of critical care medicine, the Second Affiliated Hospital of Kunming Medical University from January 2011 to December 2019 were collected. The main reasons for maternal transfer to ICU, the causes of maternal death, and organ support measures, etc. were summarized.Results:A total of 39 567 critically ill pregnant and parturient women were admitted to the department of obstetrics in our hospital, and 360 were transferred to ICU, with an average ICU transfer rate of 0.91%. Since 2016, the number of obstetric admissions, the number of ICU transfers and the ICU transfer rate had increased significantly. The average age of severe maternals admitted to ICU was (30.9±5.7) years old. The average acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score was 7 (4, 10). The average length of ICU stay was 1 (1, 2) day. The average ventilator duration was 9.0 (3.0, 17.5) hours. The main delivery mode of pregnant women in ICU was cesarean section (84.72%). Forty-eight patients (13.33%) underwent hysterectomy, of which 42 (87.5%) due to postpartum hemorrhage. The top 3 causes of ICU admission were severe postpartum hemorrhage [36.94% (133/360)], hypertensive disorders of pregnancy [21.67% (78/360)], pregnancy with cardiac disease [15.00% (54/360)]. The leading cause of postpartum hemorrhage in women transferred to ICU was placental abnormality [63.98% (103/161)], followed by uterine atony [28.57% (46/161)]. The average blood loss was (4 019±2 327) mL within 24 hours after delivery, and the number of women who underwent hysterectomy due to postpartum hemorrhage decreased year by year. During the study period, there were 2 maternal deaths, which were indirect obstetric deaths, 3 cases were discharged against-advice (expected death), including 1 indirect death and 2 direct obstetric death; the mortality in ICU was 1.39% (5/360).Conclusions:The most common reasons for pregnant and parturient women to be admitted to ICU were severe postpartum hemorrhage and hypertensive disorders of pregnancy. The leading cause of postpartum hemorrhage was placental problem. Indirect obstetric deaths exceeded direct obstetric deaths, mainly due to pregnancy complicated with cardiac disease and severe pneumonia. ICU has become an important battlefield for rescuing critically ill maternal and an important guarantee for reducing the maternal mortality.

This study was performed to investigate the impact of nobiletin(NOB)on fracture healing in osteoporosis(OP)rats through the stimulator of interferon gene(STING)/nuclear transcription factor kappa B(NF-κB)signal pathway.A rat model of OP fracture was established by ovariectomy and right femoral shaft fracture intramedullary fixation;the rats after modeling were randomly grouped into model group,high dose(NOB-H,30 mg/kg NOB),medium dose(NOB-M,20 mg/kg NOB),low dose(NOB-L,10 mg/kg NOB)NOB group and NOB-H+ STING activator(DMXAA)group(30 mg/kg NOB+25 mg/kg DMXAA),and 18 rats experienced only ovaries expose were used as sham operation group.After the intervention,the fracture healing status of rats were measured;Micro-CT was used to detect the changes of bone trabecular microstructure in rats;commercial kits were used to detect the serum levels of bone metabolism related indicators(alkaline phosphatase(ALP),calcium,phosphorus)and inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β));HE was used to detect the morphological changes and trabecular area of femur,while Western blot was applied to detect the expression of STING/NF-κB pathway related proteins.Compared with the control group,the fracture line in the model group was clear,the trabecular structure was disordered and the gap was large,furthermore,the levels of TNF-α and IL-1β,the expression of STING and p-NF-κB p65/NF-κB p65 were significantly increased,the trabecular area,the levels of ALP,calcium,phosphorus,and bone mineral density(BMD),bone volume fraction(BV/TV),bone trabecular number(Tb.N)and bone trabecular thickness(Tb.Th)were significantly decreased(P<0.05);compared with the model group,the fracture line of NOB-L group,NOB-M group and NOB-H group gradually blurred,the trabecular structure arranged orderly,and the gap gradually decreased,and the trend of the index changes mentioned above were opposite to that of the model group(P<0.05).STING activators attenuated the promotion of fracture healing by NOB in OP rats and increased the inflammatory responses.In conclusion,NOB can reduce inflammatory reaction and promote fracture healing in OP rats,which may be related to the inhibition of STING/NF-κB signal pathway.

Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.

Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of neutrophilic asthma(NA)based on network pharmacology and in vivo experiments.Methods(1)The TCMSP,literature search and Swiss ADME and Swiss Target Prediction databases were used to search and screen the active components and their targets of Shema Zhichuan Liquid.OMIM,GeneCards,DisGeNET and DrugBank databases were used to search and screen NA disease-related targets.The intersection of the active components and NA disease-related targets of Shema Zhichuan Liquid was obtained through the microbiology platform to obtain the potential targets of Shema Zhichuan Liquid for the treatment of NA(common targets).Cytoscape 3.8 software was used to construct the network of"Chinese medicinals-active components-potential targets".The PPI network of potential targets was established by STRING database,and the core targets were obtained by analysing the built-in Mcode plug-in.The Metascape platform was used to enrich the gene ontology(GO),Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathways for the potential targets.(2)BALB/C mice were acclimatised and fed for 1 week and randomly divided into a blank group,NA model group,low-dose group(2.5 g·kg-1)and high-dose group of Shema Zhichuan Liquid(10 g·kg-1),and control group of Dexamethasone(1 mg·kg-1);the NA mouse model was replicated by intraperitoneal injection of sensitizer(OVA+CFA)and nebulized inhalation excitation.OVA/CFA(20 μg OVA+75 μg CFA,0.3 mL)was injected intraperitoneally to sensitize on days 0,7 and 14 respectively,and 5%OVA suspension was nebulized on days 21-30(8 mL each time,40 minutes each time,once a day);1 hour before nebulisation,each group was administered by gastric gavage,and the Dexamethasone control group was administered by intraperitoneal injection once a day.The pathological changes of mouse lung tissue were observed by HE staining;IL-8 content in alveolar lavage fluid was detected by ELISA;mRNA expression levels of NLRP3 and CXCR2 were detected by RT-qPCR;and p-mTOR protein expression levels was detected by immunohistochemistry.Results(1)A total of 826 active component targets and 154 NA disease-related targets were obtained,and 51 potential targets(common targets)for the treatment of NA were obtained from the intersection of the active component and the NA disease-related targets of Shema Zhichuan Liquid.Through the network analysis of"Chinese medicinals-active components-potential targets",quercetin,lignocerotoxin,kaempferol,stigmasterol,naringenin and other key active components were obtained.The PPI network analysis of potential targets yielded 29 core targets,including AKT1,IL6,TNF,EGFR,NLRP3,RELA,MIF,CXCR2,VEGFA,etc..The GO functional enrichment analysis yielded 882 biological process entries,33 cellular component entries,and 61 molecular function entries;KEGG analysis yielded 142 signaling pathways,mainly involving TNF signaling pathway,influenza A signaling pathway,Toll-like receptor pathway,MAPK signaling pathway,mTOR signaling pathway and so on.(2)Results of animal experiments:compared with the blank group,mice in the NA model group showed obvious damage to the airway mucosa,structural disorders,a large number of inflammatory cells infiltration,mucosal congestion,oedema,obvious thickening of the alveolar wall,and narrowing of the alveolar lumen;the level of the inflammatory factor IL-8 in the alveolar lavage fluid was significantly elevated(P＜0.05);the mRNA expressions of NLRP3 and CXCR2 in the lung tissues of the mice were significantly up-regulated(P＜0.01),and the protein expression of p-mTOR was significantly increased.Compared with the NA model group,the structural arrangement of bronchial epithelial cells in the mice in the low-and high-dose groups of Shema Zhichuan Liquid was slightly disordered,with a small amount of inflammatory cell infiltration around the airways and blood vessels,and the congestion and edema of the bronchial mucosa were significantly reduced;the mRNA expression of CXCR2 in the lung tissues of the mice was significantly down-regulated(P＜0.01),and the level of expression of p-mTOR protein was significantly reduced.The IL-8 level in the vesicular lavage fluid of mice in the high-dose group was significantly reduced(P＜0.05);the mRNA expression of NLRP3 in the lung tissue of mice in the low-dose group was significantly down-regulated(P＜0.05).Conclusion The therapeutic effect of Shema Zhichuan Liquid on NA may be achieved through the key active components,such as quercetin,lignocerol and kaempferol,acting on the core targets,such as NLRP3 and CXCR2,and regulating the key signaling pathways,such as the TNF signaling pathway,the MAPK signaling pathway,the Toll-like signaling pathway,and the mTOR pathway.

OBJECTIVE To analyze the implementation experience of France’s additional list system for innovative medical products， and to provide reference for China to support medical institutions to use innovative medical products. METHODS Taking France as a case study， using policy analysis method， this paper systematically studied the practice of establishing additional list system to compensate for innovative medical products in France under diagnosis-related group （DRG） payment， including the establishment background， selection procedure and implementation effect. The suggestions were provided on the medical insurance payment methods for innovative medical products in China. RESULTS & CONCLUSIONS The additional list system established a compensation and payment system for innovative medical products with significant clinical efficacy but high treatment cost， covering four stages： application， evaluation， payment and adjustment， which effectively reduced the drug burden on medical institutions， promoted the use of innovative pharmaceutical products by medical institutions， and stimulated the innovation drive of the pharmaceutical industry， but at the same time brought payment pressure to the medical insurance fund. With the rapid spread of our DRG/diagnosis-intervention packet payment reform of China， some regions have also explored the establishment of a compensation and payment mechanism for innovative medical products， but there are still imperfections. We can refer to the implementation experience of the French additional list system and establish an effective compensation and payment system for innovative medical products starting from the establishment of selection criteria， the selection of compensation mode and the implementation of dynamic adjustment.