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*

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

Surgical operation is the main treatment method for pancreatic cancer, and in clinical practice, radical surgery for pancreatic cancer is often combined with superior mesenteric-portal vein confluence pancreaticoduodenectomy to achieve R0 resection. However, severe left-sided portal hypertension (LSPH) may occur after splenic vein dissection, resulting in a series of pathological changes such as congestive splenomegaly, thrombocytopenia, backflow obstruction of splenic vein, and gastrointestinal varices, and in some cases, it can lead to fatal gastrointestinal hemorrhage and hemorrhagic shock. Therefore, in order to better manage LSPH in clinical practice, this article systematically analyzes and reviews the pathogenesis, treatment regimens, and control strategies of LSPH after combined superior mesenteric-portal vein confluence pancreaticoduodenectomy and put forward corresponding suggestions based on current studies.

Objective:To investigate the influencing factors of the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 431 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2013 to December 2020 were retrospectively analyzed. Univariate and multivariate time-dependent covariate Cox regression model were constructed. The relationship between the clinical characteristics and prognosis of patients was analyzed.Results:The age, tumor diameter, tumor width all met the proportion hazard hypothesis (correlation coefficients were 0.044, -0.015, and -0.680, respectively, all P > 0.05). The effects of disease grade, erythrocyte sedimentation rate (ESR) increased or not, and CD20 positive or not on survival time changed with time change. When the above indicators did not meet the proportional hazard hypothesis, they were time-dependent covariables (all P < 0.05). Time-dependent covariate Cox regression multivariate analysis showed that lactate dehydrogenase (LDH) increased or not ( χ2 = 13.78, P < 0.001), β 2 microglobulin (β 2-MG) increased or not ( χ2 = 5.36, P = 0.021), tumor diameter ( χ2 = 4.12, P = 0.042) and CD20 positive or not ( χ2 = 7.09, P = 0.008) and ESR increased or not ( χ2 = 5.46, P = 0.019) were independent influencing factors of the death of DLBCL patients. Conclusions:Patients with elevated LDH, increased β 2-MG, tumor diameter, increased ESR and CD20 positive have poor prognosis. Clinicians should take further treatment measures for these patients to reduce the mortality.

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

Objective:To observe the peripapillary atrophy (PPA) and peripapillary choroidal vascularity index (CVI) in patients with different degrees of myopia and to analyze their correlations.Methods:A cross-sectional clinical study. From September 2021 to December 2021, 281 mypoic patients of 281 eyes treated in Eye Hospital of Wenzhou Medical University at Hangzhou were included in this study, and the right eye was used as the treated eye. There were 135 eyes in 135 males and 146 eyes in 146 females. The age was 28.18±5.78 years. The spherical equivalent refraction (SE) was -5.13±2.33 D. The patients were divided into three groups: low myopia group (group A, -3.00 D

Objective:To explore the positive rate of scanning laser ophthalmoscope in the retromode (RM-SLO) in different types of diabetic macular edema (DME), and to analyze its correlation with foveal thickness (CMT) and macular volume.Methods:From March to May 2021, 40 patients (65 eyes) were diagnosed as DME by fundus examination combined with optical coherence tomography (OCT) in Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. All eyes underwent best corrected visual acuity (BCVA), OCT and RM-SLO fundus imaging examinations, 47 eyes underwent fluorescein fundus angiography (FFA) examination. RM-SLO fundus imaging examinations were performed with Mirante SLO, including retro mode illumination deviated right (RMDR) and retro mode illumination deviated left (RMDL). If one or more of the RMDR and RMDL of the examined patient can identify macular edema, RM-SLO was considered to be able to identify macular edema. The macular volume at CMT and 6 mm from the fovea was measured by OCT software. DME were divided into 3 types based on OCT images: diffuse retinal thinkening (DRT) type; cystoid macular edema(CME) type; serous retinal detachment (SRD) type, focal leakage type, diffuse leakage type and diffuse cystic leakage type. The consistency of RMDR and RMDL in the diagnosis of DME in RM-SLO fundus imaging was evaluated, as well as their positive rate in different classifications of DME. The correlation between the detection of macular edema by RM-SLO and the DME type, CMT and foveal volume, and the correlation between BCVA and edema type, CMT and macular volume were analyzed.Results:Among 65 eyes, the positive rates of RMDR and RMDL fundus imaging to detect DME were 46 (70.77%, 46/65) and 48 (73.85%, 48/65), respectively. There was good consistency in identifying DME (Kappa value=0.770; P<0.001). The positive rates of RMDR and RMDL fundus imaging DRT, CME and SRD type of DME were 42.11% (8/19), 57.89% (11/19), 77.78% (28/36), 77.78% (28/36), 100.00% (10/10), 90.00% (9/10), respectively. In the FFA classification of them, the positive rates of focal leakage, diffuse leakage and diffuse cystic leakage were 68.75% (11/16), 62.50% (10/16), 68.00% (17/25), 76.00% (19/25), 100.00% (6/6), 100.00% (6/6), respectively. The results of Spearman correlation analysis showed that whether RM-SLO could identify DME was associated with CMT and OCT classification ( r=0.310, 0.365; P=0.120, 0.003); there was no correlation between FFA classification and macular volume ( r=0.113, 0.117; P=0.449, 0.352). BCVA was correlated with CMT and macular volume ( r=0.307, 0.269; P=0.013, 0.030), however, there was no significant correlation with OCT type, angiographic type ( r=0.051, 0.175; P=0.684, 0.240). Conclusion:The diagnostic agreement of DME are good between RMDR, RMDL of RM-SLO image. DME of DRT type and patients with smaller CMT in OCT are difficult to identified by RM-SLO fundus imaging.

Objective:To explore the application effect of active risk nursing procedures in neonatal hypoxic-ischemic encephalopathy (HIE) .Methods:A total of 78 children with HIE who were treated in Jinhua Maternal and Child Health Care Hospital from August 2017 to August 2019 were selected as the research objects. According to different nursing plans, they were divided into the control group and the observation group, with 39 cases in each group. The control group adopted conventional nursing, while the observation group conducted objective analysis on the potential risk factors existing in conventional nursing and designed and implemented active risk nursing procedures. The clinical symptom improvement time, length of hospital stay, total nursing satisfaction score of family members and total incidence of complications of HIE children were compared between the two groups.Results:The disappearance time of brain edema, the recovery time of muscle tension and the length of hospital stay in the observation group were shorter than those in the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the total satisfaction score of family members of the children in the observation group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The total incidence of complications in the observation group was lower than that in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:Active risk nursing procedures can effectively shorten the improvement time of clinical symptoms, shorten the length of hospital stay, improve the total nursing satisfaction of family members, reduce the total incidence of complications and improve the quality of nursing in HIE children.