BACKGROUND: The FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial demonstrated that percutaneous coronary intervention (PCI) lesion selection using quantitative flow ratio (QFR) measurement, a novel angiography-based approach for estimating fractional flow reserve, improved two-year clinical outcomes compared with standard angiography guidance. This study aimed to assess the cost-effectiveness of QFR-guided PCI from the perspective of the current Chinese healthcare system. METHODS: This study is a pre-specified analysis of the FAVOR III China trial, which included 3825 patients randomized between December 25, 2018, and January 19, 2020, from 26 centers in China. Patients with stable or unstable angina pectoris or those ≥72 hours post-myocardial infarction who had at least one lesion with a diameter stenosis between 50% and 90% in a coronary artery with a ≥2.5 mm reference vessel diameter by visual assessment were randomized to a QFR-guided strategy or an angiography-guided strategy with 1:1 ratio. During the two-year follow-up, data were collected on clinical outcomes, quality-adjusted life-years (QALYs), estimated costs of index procedure hospitalization, outpatient cardiovascular medication use, and rehospitalization due to major adverse cardiac and cerebrovascular events (MACCE). The primary analysis calculated the incremental cost-effectiveness ratio (ICER) as the cost per MACCE avoided. An ICER of ¥10,000/MACCE event avoided was considered economically attractive in China. RESULTS: At two years, the QFR-guided group demonstrated a reduced rate of MACCE compared to the angiography-guided group (10.8% vs . 14.7%, P <0.01). Total two-year costs were similar between the groups (¥50,803 ± 21,121 vs . ¥50,685 ± 23,495, P = 0.87). The ICER for the QFR-guided strategy was ¥3055 per MACCE avoided, and the probability of QFR being economically attractive was 64% at a willingness-to-pay threshold of ¥10,000/MACCE avoided. Sensitivity analysis showed that QFR-guided PCI would become cost-saving if the cost of QFR were below ¥3682 (current cost: ¥3800). Cost-utility analysis yielded an ICER of ¥56,163 per QALY gained, with a 53% probability of being cost-effective at a willingness-to-pay threshold of ¥85,000 per QALY gained. CONCLUSION: In patients undergoing PCI, a QFR-guided strategy appears economically attractive compared to angiographic guidance from the perspective of the Chinese healthcare system. TRIAL REGISTRATION ClinicalTrials.gov , NCT03656848.
Humans ; Cost-Benefit Analysis ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Angiography/methods* ; Middle Aged ; Aged ; Coronary Artery Disease/surgery* ; Quality-Adjusted Life Years ; Fractional Flow Reserve, Myocardial/physiology*

OBJECTIVES: To investigate the mechanism mediating the regulatory effect of miR-155-5p on proliferation of human submandibular gland epithelial cells (HSGECs) in primary Sjogren's syndrome (pSS). METHODS: Dual luciferase reporter assay was used to verify the targeting relationship between miR-155-5p and the PI3K/AKT pathway. In a HSGEC model of pSS induced by simulation with TRAIL and INF-γ, the effects of miR-155-inhibitor-NC or miR-155 inhibitor on cell viability, cell cycle, apoptosis and proliferation were evaluated using CKK8 assay, flow cytometry and colony formation assay. ELISA and RT-PCR were used to detect the expressions of inflammatory cytokines and miR-155-5p mRNA in the cells; Western blotting was performed to detect the expressions of proteins in the PI3K/AKT signaling pathway. RESULTS: Dual luciferase assay showed that miR-155-5p targets the PI3K/AKT pathway via PIK3R1 mRNA. The HSGEC model of pSS showed significantly decreased cell viability, cell clone formation ability and expressions IL-10 and IL-4 and increased cell apoptosis, cell percentage in G2 phase, expressions of TNF‑α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-Akt/AKT ratio, and PIK3R1 protein expression. Treatment of the cell models with miR-155 inhibitor significantly increased the cell viability, G1 phase cell percentage, colony formation ability, and expressions of IL-10 and IL-4 levels, and obviously reduced cell apoptosis rate, G2 phase cell percentage, expressions of TNF-α, IL-6, miR-155-5p and PIK3R1 mRNA, p-PI3K/PI3K ratio, p-AKT/AKT ratio, and PIK3R1 protein expression. CONCLUSIONS In HSGEC model of pSS, inhibition of miR-155-5p can promote cell proliferation and reduced cell apoptosis by targeting PI3K1 mRNA to negatively regulate the overexpression of PI3K/AKT signaling pathway.
Humans ; MicroRNAs/genetics* ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Sjogren's Syndrome/pathology* ; Epithelial Cells/cytology* ; Submandibular Gland/cytology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Class Ia Phosphatidylinositol 3-Kinase ; Cells, Cultured

Objective To observe the effect of ultrasound-guided iliopsoas plane block(IPB)on the quality of postoperative recovery in patients undergoing hip arthroplasty.Methods Sixty patients who underwent hip arthroplasty were selected,37 males and 23 females,aged 40-79 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ.The patients were divided into two groups by random number table method:the iliopsoas plane block group(group IPB)and the femoral nerve block(FNB)group(group FNB),30 pa-tients in each group.Before anesthesia induction,IPB was performed with 0.5%ropivacaine 10 ml and lat-eral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group IPB.And FNB was performed with 0.5%ropivacaine 10 ml and lateral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group FNB.The dosages of propofol,remifentanil,and cis-atracurium during operation were recorded.The quality of recovery-15(QoR-15)scale was evaluated preoperatively and postoperatively 1 day,2 and 3 days.The max VAS(VASmax)pain score and manual muscle test(MMT)score of quadri-ceps muscle were recorded 12,24,and 48 hours after surgery.The time of getting out of bed for the first time,opioid dosage,and patient satisfaction were recorded.The incidence of nerve injury,vascular injury,puncture site infection,and local anesthetic poisoning were recorded.The postoperative complications of diz-ziness,nausea and vomiting,deep vein thromboses,and elirium were also recorded.Results There was no significant difference in the dosage of propofol,remifentanil,and cis-atracurium between the two groups.Compared with group FNB,the QoR-15 scale score in group IPB was significantly higher 1 day,2 and 3 days after operation(P＜0.05).Compared with group FNB,the MMT scores of quadriceps muscle was sig-nificantly higher in group IPB 12 and 24 hours after surgery(P＜0.05),and the first time of getting out of bed was shortened in group IPB(P＜0.05).However,there were no significant differences in the VASmax pain score,MMT score of quadriceps muscle 48 hours after surgery,opioid dosage,and patient satisfaction between the two groups.No nerve block related complications were found in both groups.There were no sig-nificant differences in postoperative complications between the two groups.Conclusion The iliopsoas plane block can improve the quality of postoperative recovery and accelerate the recovery of patients with hip re-placement,and the effect is better than that of femoral nerve block.

Objective:To investigate the efficacy of transcatheter arterial embolization (TAE) in treating postoperative hemorrhage in the gallbladder-pancreas-duodenum(GPD) region.Methods:The clinical data of 39 patients with postoperative hemorrhage in the GPD region who underwent digital subtraction angiography (DSA) examination in Peking Union Medical College Hospital from July 2018 to August 2022 were analyzed retrospectively, clinical regression was compared between TAE-treated and non-TAE-treated patients, and the concordance between DSA and enhanced CT for bleeding indications was analyzed using the Kappa test.Results:Among 39 patients, DSA examination suggested bleeding in 26 patients (66.7%), which were gastroduodenal artery hemorrhage in 4 cases, common hepatic artery and branches in 6 categories, superior mesenteric artery and branches in 6 cases, pancreaticoduodenal artery and branches in 4 cases, pancreatic aorta in 3 cases, splenic artery in 2 cases, and gastric left artery in 1 case. Positive DSA signs manifested as contrast spillage alone in 18 cases (69.2%), pseudoaneurysm alone in 7 cases (26.9%), and pseudoaneurysm with contrast spillage in 1 case (3.8%). 26 patients underwent TAE with a technical success rate of 96.2% (25/26), a clinical success rate of 88.5% (23/26) and a rebleeding rate of 7.7% (2/26). 13 patients didn't undergo TAE and the rebleeding rate was 30.8%(4/13). 14 patients underwent enhanced CT in the same period of DSA, showed low concordance with DSA in determining the presence or absence of bleeding, with a Kappa value of 0.462.Conclusions:TAE is a safe and effective treatment for postoperative hemorrhage in the GPD region. Patients without TAE treated should be alert for rebleeding. When postoperative hemorrhage is suspected, the consistency between enhanced CT and DSA examination results is limited, and DSA examination should be preferred.

Objective To observe the effect of opioid-free anesthesia with esketamine and ciprofol for the elderly underwent colonoscopy.Methods 160 elderly patients underwent colonoscopy were included in this study.Those patients were assigned to esketamine combined with ciprofol group(group E,n = 80)and sufentanil combined with ciprofol(group S,n = 80).Patients were intravenously injected respectively with esketamine 0.2 mg/kg in group E and sufentanil 0.1 μg/kg in group S.Then,all the patients were intravenously injected with ciprofol(0.2 mg/kg).Mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)were recorded before injection of test drug(T0),when modified observer's assessment of alertness/sedation(MOAA/S)score was 0 points(T1),when colonoscopy through hepatic flexure(T2)and colonoscopy was removed after examination(T3).The induction time of anesthesia,time of fully awake,rate of successful anesthesia,additional dose of ciprofol,satisfaction score and incidence of adverse events were recorded.Results Compared with T0,MAP at T1,T2 and T3 in two groups was decreased,HR at T1 in group E,HR at T1,T2 and T3 in group S and SpO2 at T1 and T2 in group S were decreased,the differences were statistically significant(P<0.05).Compared with T1,MAP and HR at T2 in two groups were increased,the differences were statistically significant(P<0.05).Compared with group E,MAP in group S at T1,T2 and T3,HR and SpO2 at T1 and T2 in group E were decreased,the differences were statistically significant(P<0.05).Compared with the group E,the additional dosage of ciprofol,the incidence of hypoxemia and hypotension were increased,the satisfaction of anesthesiologists was decreased in group S,the differences were statistically significant(P<0.05).Conclusion For opioid-free anesthesia,esketamine is feasible for colonoscopy anesthesia in elderly patient,and the incidence of hypoxemia and hypotension is low.

Objective To observe CT and MRI manifestations of lipofibromatosis(LPF)in children.Methods Data of 16 children with LPF confirmed by pathology were retrospectively analyzed,and CT and MRI manifestations of lesions were observed.Results Among 16 cases,lesions with clear boundary were found in 4 cases but with unclear boundary in 12 cases,shaped regularly in 6 cases but irregularly in 10 cases,with incomplete capsule in 2 cases but without capsule in 14 cases.Fat predominant type lesions were detected in 6 cases,mainly characterized by scattered fibrous bands in the center or cloud like soft tissue density/signal on one side of lesion,without obvious boundary.Fibrous dominant type lesions were noticed in 8 cases,mainly present as loose morphology,multiple fibrous bands extending to surrounding area,with scattered cystic fat density/signal within the lesion.Balanced type LPF lesion was observed in 2 cases,mainly manifestated as regular shape mixed density/signal lesion with clear boundary.Among 12 cases who underwent enhanced scanning,mild progressive enhancement in the non-fat area were observed in 7 cases,obvious peripheral enhancement but not obvious central enhancement was found in 2 case,obvious homogeneous enhancement was noticed in 1 case,while no obvious enhancement was found in 2 cases.No obvious calcification,cystic changes nor bone destruction was detected.Conclusion CT and MRI manifestations of LPF included subcutaneous fat containing density/signal,often composed mainly of adipocytes or fibrous components,with mild progressive enhancement or significant enhancement,without obvious capsule,calcification,cystic changes nor bone destruction.

Objective:To analyze the influencing factors of clozapine plasma concentration in patients with mental disorders after oral administration, so as to provide reference for individualized treatment.Methods:Retrospective analysis was made on 221 inpatient reports of Clozapine blood concentration monitoring in the Therapeutic Drug Monitoring Laboratory (TDM) of the Pharmacy Department of the Chaohu Hospital Affiliated to Anhui Medical University from January to October 2021, and information such as patient gender, age, body mass index (BMI), smoking history, clozapine dose, combined drug use and blood concentration monitoring results were collected; Single factor analysis of variance and binary logistic regression were used to analyze the monitoring results of clozapine blood concentration in patients with mental disorders and its influencing factors.Results:Among 221 monitoring reports, 74 cases (normal concentration group) had clozapine plasma concentration within the effective plasma concentration range (350-600 ng/ml), 103 cases (low concentration group) were lower than the effective plasma concentration range (<350 ng/ml), and 44 cases (high concentration group) were higher than the effective plasma concentration range (>600 ng/ml). The results of single factor analysis of variance showed that there were statistically significant differences in daily dose of clozapine, standard dose, smoking history, course of disease, and abnormal liver function of patients in different blood concentration groups of clozapine (all P<0.05). The most frequently used antipsychotic drugs in 221 patients with clozapine were sodium valproate, amisulpride, aripiprazole and lithium carbonate in turn. The proportion of clozapine combined with ≥2 antipsychotics in the normal concentration group was higher than that in the low concentration group and the high concentration group, and the difference was statistically significant ( P<0.05). The results of binary logistic regression analysis showed that the combination of one antipsychotic drug and ≥ two antipsychotic drugs might help the blood concentration of clozapine in patients with mental disorders reach the target concentration (350-600 ng/ml), and the combination of two drugs was more beneficial [ OR(95% CI): 1.795(0.753-4.282)], with a statistically significant difference ( P<0.05). Conclusions:Clozapine plasma concentration varies greatly among individuals, and the therapeutic window is narrow. It is necessary to adjust the dosage in combination with the basic information and clinical information of patients, and regularly monitor the plasma concentration, so as to achieve the safety and effectiveness of individualized drug use.

Pulmonary fibrosis(PF)is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2-3 years.The inhibition of transforming growth factor-β receptor type-Ⅰ(TGF-β RI)by an appropriate drug may provide a promising strategy for the treatment of this disease.Polygonum cuspidatum(PC)is a well-known traditional Chinese herbal medicine which has an anti-PF effect.Accordingly,a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI.Based on this strategy,a total of 24 ingredients were identified.Then,absorption,distribution,meta-bolism,and excretion(ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour.Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors.Eventually,a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI,with an ICso of 2.211 μM in vitro.Furthermore,the complex formed through molecular docking was tested via molecular dynamics simulations,which revealed that resveratrol had strong interactions with residues of TGF-β RI.This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI.In addition,this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

Objective:To investigate the levels of serum pyrolysis-related factors cysteine protease-1 (caspase-1) and interleukin-18 (IL-18) in patients with gestational diabetes mellitus (GDM) and their relationship with insulin resistance (IR) .Methods:A total of 102 GDM patients admitted to Kaifeng Traditional Chinese Medicine Hospital from Apr. 2019 to Mar. 2021 were selected as the GDM group, and 102 healthy pregnant women undergoing obstetric examination in the same period were included as the normal group. The age, gestational week, fasting insulin (FINS) , pre-pregnancy body mass index (BMI) , triglycerides (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , and homeostatic model insulin resistance index (HOMA-IR) and other materials were compared between the GDM group and the normal group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum caspase-1 and IL-18; Pearson method was used to analyze the correlation between serum caspase-1 and IL-18 levels and HOMA-IR in GDM patients; Logistic regression method was used to analyze the influencing factors of GDM.Results:The levels of TG [ (2.94±0.99) mmol/L vs (2.09±0.70) mmol/L], FBG [ (5.87±1.94) mmol/L vs (4.90±1.67) mmol/L], TC [ (5.72±1.92) mmol/L vs (5.03±1.68) mmol/L], FINS [ (11.45±3.87) mIU/L vs (6.92±2.34) mIU/L], HOMA-IR [ (3.05±0.78) vs (1.51±0.40) ] and levels serum caspase-1 [ (86.27±28.78) pg/mL vs (40.98±13.54) pg/mL] and IL-18 [ (44.26±14.56) pg/L vs (30.45±10.12) pg/L] in the GDM group were higher than those in the normal group (t=7.080, 3.827, 2.731, 10.116, 17.743, 14.381, 7.866, P<0.05) ; the levels of serum caspase-1 and IL-18 in GDM patients were positively correlated with HOMA-IR ( r=0.518, 0.555, P<0.05) ; FBG, TG, FINS, HOMA-IR, caspase-1, IL-18 were risk factors affecting the occurrence of GDM (95% CI=1.578-3.826, 1.454-3.311, 1.477-3.405, 1.678-4.265, 1.406-3.141, 1.511-3.551, P<0.05) . Conclusions:The levels of serum caspase-1 and IL-18 in patients with GDM are relatively high, which are significantly related to IR. Caspase-1 and IL-18 may be potential targets for the treatment of GDM.

［摘要］ 目的：寻找多发性骨髓瘤（MM）基因芯片数据集中的潜在致病基因、疾病诊断和预后相关因子并阐明其作用机制。 方法：获取基因芯片数据集GSE13591 和Zhan Myeloma，使用R 语言进行基因差异表达分析。对共同高表达基因进行Meta 分 析，得到P 值中位秩次TOP10 基因。CCLE 数据库分析TOP10 基因在各肿瘤细胞系中的mRNA表达情况，筛选出蛋白酶体通路 相关基因8（DCAF8）。cBioPortal 数据库中分析DCAF8 基因在各肿瘤细胞系的突变率。WB检测DCAF8 蛋白在骨髓瘤细胞系中 的表达情况。SPSS 和Graph Pad 软件分析DCAF8 表达量和MM患者临床特征之间的相关性，进行受试者工作特征曲线（ROC曲 线）绘制和生存分析。R语言Custer Profiler Package 和Metascape 数据库对DCAF8 互作蛋白基因和共表达基因进行GO和KEGG 功能富集分析。结果：数据集GSE13591 和Zhan Myeloma 的上调基因取交集得到477 个共同高表达基因。在合并数据集中对上 述基因进行Meta 分析，得到P 值中位秩次TOP10 基因，DCAF8 在MM细胞系中的平均表达水平最高。DCAF8 基因在浆细胞骨 髓瘤中的突变率位于各肿瘤细胞系的第一位。DCAF8 蛋白在多种MM细胞系中的表达量显著升高（P<0.01）。DCAF8 表达量与 MM患者的肿瘤负荷显著正相关，1q21 扩增阳性组的DCAF8 的表达量显著高于1q21 阴性组。ROC曲线显示DCAF8 的表达水平 可以很好地区分MM患者和正常人（P<0.01）。DCAF8 高表达组比DCAF8 低表达组中位生存时间显著缩短。蛋白互作网络显示 DCAF8 可与XPO1 蛋白直接相互作用。GO和KEGG功能富集分析结果表明，DCAF8 与蛋白酶体功能、剪切体活性、组蛋白乙酰 化酶活性、RNA转运等功能相关。结论：DCAF8 在MM中显著高表达，其表达水平可以很好地区分MM患者和正常人；其高表 达与MM患者的生存预后显著负相关，且与1q21 扩增和XPO1 蛋白相关。