Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

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.

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*

Objective:To investigate the hemodynamic characteristics of frontal cortex and bilateral temporal lobes in patients with obsessive-compulsive disorder (OCD) during verbal fluency tasks using functional near-infrared spectroscopy (fNIRS), and assess the value of fNIRS in aiding OCD diagnosis.Methods:Clinical data of 30 OCD patients who visited the Psychology Department at Ruijin Hospital, affiliated with the Shanghai Jiaotong University School of Medicine between June 2022 and June 2023 were prospectively collected. There were 17 males and 13 females aged 16-41 years, and the education level was 9-19 years. Another 30 healthy control participants voluntarily participated in the study, including 12 males and 18 females aged 19-54 years with 9-19 years of education. Cerebral hemodynamic changes in the prefrontal and bilateral temporal lobes were detected using fNIRS during verbal fluency tasks. Specific parameters including integral values, centroid values, and slopes for both the prefrontal and bilateral temporal lobes were analyzed using independent two-sample t-tests and non-parametric Mann-Whitney U tests. Influencing indicators for OCD were analyzed using a binary logistic regression model. Receiver Operating Characteristic (ROC) curve analysis was plotted to evaluate the diagnostic performance of fNIRS indicators in distinguishing OCD patients from healthy controls, and the optimal cutoff value were calculated. Results:OCD patients generated significantly less words during the verbal fluency task compared to healthy controls ( M( Q1, Q3)) (Number of 9.0 (7.0, 12.0) vs 12.0 (10.0, 16.3), Z=2.80, P=0.005). The integral values and slopes of the frontal lobe, and the integral values of the bilateral temporal lobes, were significantly lower in OCD patient group (32.3 (-7.8, 62.2) vs 123.7 (96.2, 181.3), Z=5.76; 0.000 5±0.001 2 vs 0.001 5±0.001 6, t=-2.54; 87.0±71.4 vs 186.1±90.3, t=-4.71), while centroid values of both the frontal and bilateral temporal lobes were higher ((60.4±13.8) seconds vs (54.4±7.8) seconds, t=2.80; 60.3 (55.5, 65.0) seconds vs 56.2 (52.7, 59.2) seconds, Z=-2.42), with all the differences statistically significant (all P<0.05). No significant difference was observed in slope of bilateral temporal lobes between two groups ( t=-1.60, P=0.116). Binary logistic regression showed that integral value of frontal cortex significantly influenced OCD occurrence ( OR=0.958, 95% CI: 0.932-0.985, P=0.003). ROC analysis indicated ideal diagnostic performance of integral value of frontal lobe in distinguishing OCD patients from healthy controls with an optimal cut-off value of 68.2, sensitivity of 0.900, specificity of 0.833, and AUCs of 0.931 (95% CI: 0.869-0.993, P<0.001). AUCs of number of words generated, integral value of frontal cortex, slope of frontal cortex, integral value of bilateral temporal lobes, and centroid value of bilateral temporal lobes were 0.709 (95% CI: 0.580-0.839), 0.931 (95% CI: 0.869-0.993), 0.665 (95% CI: 0.527-0.803), 0.793 (95% CI: 0.683-0.904), and 0.682 (95% CI: 0.542-0.822), respectively (all P<0.05). Centroid value of frontal cortex showed poor diagnostic performance (AUC=0.637, 95% CI: 0.493-0.781, P=0.069). Conclusion:OCD patients generated less words and have decreased integrated values and increased centroid values of frontal cortex and bilateral temporal lobes during verbal fluency tasks. Integral values of frontal cortex significantly influence OCD occurrence and demonstrate high sensitivity and specificity in distinguishing OCD patients from healthy controls.

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.

Objective:To investigate the hemodynamic characteristics of frontal cortex and bilateral temporal lobes in patients with obsessive-compulsive disorder (OCD) during verbal fluency tasks using functional near-infrared spectroscopy (fNIRS), and assess the value of fNIRS in aiding OCD diagnosis.Methods:Clinical data of 30 OCD patients who visited the Psychology Department at Ruijin Hospital, affiliated with the Shanghai Jiaotong University School of Medicine between June 2022 and June 2023 were prospectively collected. There were 17 males and 13 females aged 16-41 years, and the education level was 9-19 years. Another 30 healthy control participants voluntarily participated in the study, including 12 males and 18 females aged 19-54 years with 9-19 years of education. Cerebral hemodynamic changes in the prefrontal and bilateral temporal lobes were detected using fNIRS during verbal fluency tasks. Specific parameters including integral values, centroid values, and slopes for both the prefrontal and bilateral temporal lobes were analyzed using independent two-sample t-tests and non-parametric Mann-Whitney U tests. Influencing indicators for OCD were analyzed using a binary logistic regression model. Receiver Operating Characteristic (ROC) curve analysis was plotted to evaluate the diagnostic performance of fNIRS indicators in distinguishing OCD patients from healthy controls, and the optimal cutoff value were calculated. Results:OCD patients generated significantly less words during the verbal fluency task compared to healthy controls ( M( Q1, Q3)) (Number of 9.0 (7.0, 12.0) vs 12.0 (10.0, 16.3), Z=2.80, P=0.005). The integral values and slopes of the frontal lobe, and the integral values of the bilateral temporal lobes, were significantly lower in OCD patient group (32.3 (-7.8, 62.2) vs 123.7 (96.2, 181.3), Z=5.76; 0.000 5±0.001 2 vs 0.001 5±0.001 6, t=-2.54; 87.0±71.4 vs 186.1±90.3, t=-4.71), while centroid values of both the frontal and bilateral temporal lobes were higher ((60.4±13.8) seconds vs (54.4±7.8) seconds, t=2.80; 60.3 (55.5, 65.0) seconds vs 56.2 (52.7, 59.2) seconds, Z=-2.42), with all the differences statistically significant (all P<0.05). No significant difference was observed in slope of bilateral temporal lobes between two groups ( t=-1.60, P=0.116). Binary logistic regression showed that integral value of frontal cortex significantly influenced OCD occurrence ( OR=0.958, 95% CI: 0.932-0.985, P=0.003). ROC analysis indicated ideal diagnostic performance of integral value of frontal lobe in distinguishing OCD patients from healthy controls with an optimal cut-off value of 68.2, sensitivity of 0.900, specificity of 0.833, and AUCs of 0.931 (95% CI: 0.869-0.993, P<0.001). AUCs of number of words generated, integral value of frontal cortex, slope of frontal cortex, integral value of bilateral temporal lobes, and centroid value of bilateral temporal lobes were 0.709 (95% CI: 0.580-0.839), 0.931 (95% CI: 0.869-0.993), 0.665 (95% CI: 0.527-0.803), 0.793 (95% CI: 0.683-0.904), and 0.682 (95% CI: 0.542-0.822), respectively (all P<0.05). Centroid value of frontal cortex showed poor diagnostic performance (AUC=0.637, 95% CI: 0.493-0.781, P=0.069). Conclusion:OCD patients generated less words and have decreased integrated values and increased centroid values of frontal cortex and bilateral temporal lobes during verbal fluency tasks. Integral values of frontal cortex significantly influence OCD occurrence and demonstrate high sensitivity and specificity in distinguishing OCD patients from healthy controls.

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.

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