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*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

OBJECTIVE: To investigate the current status of long-term quality of life in patients with severe acute pancreatitis (SAP) who have been cured and discharged, and to analyze the influencing factors affecting long-term quality of life in SAP cured patients after discharge. METHODS: A retrospective collection was conducted. Patients who were received standardized treatment before being cured and discharged from the hospital admitted to the first department of critical care medcine of the Second Affiliated Hospital of Anhui Medical University from January 2017 to December 2023 were enrolled. According to the 36-item short form health survey scale (SF-36) score, patients were divided into high score group (high quality of life, the top 50% of patients with total SF-36 score) and low score group (low quality of life, the bottom 50% of patients with total SF-36 score). The gender, age, history of hypertension and diabetes, etiology of pancreatitis, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), CT severity index (CTSI), laboratory indicators such as C-reactive protein (CRP), procalcitonin (PCT), blood glucose, and triglycerides upon admission, use of vasoactive drugs, non-invasive/high-flow ventilation, invasive ventilation, retroperitoneal puncture and drainage, open pancreatic surgery treatment and secondary infection during hospitalization were collected, as well as the retention of abdominal drainage tubes at discharge from hospital. Distribute follow-up questionnaires or telephone follow-up surveys through WeChat and Question Star programs to investigate the pancreatic secretion function, chronic abdominal pain, and recurrence of pancreatitis of patients after discharge. Multivariable Logistic regression was used to analyze the relevant factors affecting the long-term quality of life of cured patients with SAP. RESULTS: A total of 86 patients were ultimately enrolled. There were 43 patients in both the high and low score groups. Among 86 patients, 20 experienced acute pancreatitis recurrence, with a recurrence rate of 23.26%. Twenty-two (25.58%) experienced chronic abdominal pain after discharge, and 5 patients (5.81%) needed medication to relieve pain. Thirty-three patients (38.37%) had pancreatic exocrine dysfunction after discharge, characterized by abdominal distension, constipation or diarrhea. Twenty-two patients (25.58%) suffered from pancreatic endocrine dysfunction, and were diagnosed with diabetes. Univariate analysis showed that compared with the high score group, the low score group had more patients with hypertension, initial renal dysfunction, initial severe metabolic acidosis, initial serum calcium < 2.0 mmol/L, blood glucose > 11.1 mmol/L and cultured Gram positive bacteria (from blood/body fluid/pancreatic necrotic tissue) during treatment (48.84% vs. 16.28%, 60.47% vs. 32.56%, 18.60% vs. 4.65%, 88.37% vs. 62.79%, 55.81% vs. 30.23%, 34.88% vs. 13.95%), had higher CTSI score (6.60±1.61 vs. 5.77±1.32), lower hemoglobin level at discharge (g/L: 102.30±18.78 vs. 110.72±16.68), and a lower proportion of etiological interventions after discharge (34.88% vs. 67.44%), the differences were statistically significant (all P < 0.05). Multivariate Logistic regression analysis showed that hypertension [odds ratio (OR) = 4.814, 95% confidence interval (95%CI) was 1.196-19.378], initial serum calcium < 2.0 mmol/L (OR = 6.688, 95%CI was 1.321-33.873) and initial blood glucose > 11.1 mmol/L (OR = 6.473, 95%CI was 1.399-29.950) were risk factors for long-term quality of life in cured SAP patients (all P < 0.05), while post discharge prophylactic intervention was a protective factor for long-term quality of life (OR = 0.092, 95%CI was 0.020-0.425, P < 0.01). CONCLUSIONS Cured SAP patients have varying degrees of impaired secretion function and the possibility of recurrence of acute pancreatitis. Hypertension, initial serum calcium < 2.0 mmol/L and blood glucose > 11.1 mmol/L are independent influencing factors for low long-term quality of life in cured SAP patients. Prevention and intervention targeting the etiology of pancreatitis after discharge can improve the long-term quality of life of cured SAP patients.
Humans ; Quality of Life ; Retrospective Studies ; Pancreatitis/therapy* ; Patient Discharge ; Male ; Female ; Middle Aged ; APACHE ; Adult ; Acute Disease ; Aged

Objective The aim of this study is to retrospectively analyze the clinical and imaging characteristics,treatment and prognosis of 13 patients with granulomatous prostatitis(GP),and to provide reference for the diagnosis and treatment for GP.Methods The clinical information of 13 GP patients extracted from electronic medical records including demographic characteristic risk factors,clinical symptoms,laboratory findings,imaging findings(ultrasound,CT,MRI,FDG-PET-CT),treatment and outcomes were analyzed retrospectively from January 2018 to August 2023 at our center.Results The average age of 13 patients with GP was(65.69±6.46)years.And the average score of IPSS was(23.40±5.8).Five patients appeared positive results,of which 11 cases received digital rectal examination.The average level of pre-biopsy tPSA was(23.28±44.94)μg/L with fPSA/tPSA ratio of 0.11±0.05 and PSAD of(0.55±1.07)μg/l/mL.The pre-biopsy mean MRI PI-RADS 2.0 was(4.6±0.6)in this group of patients.Extraprostatic invasion was shown on imaging in 4 patients.The average number of biopsy needles was(19.6±3.9),and the pathological results showed tuber-culous granulomas in 2 cases(15.4％)and non-specific granulomatous inflammation in 11 cases(84.6％).Five patients received local treatment of the prostate after pathological confirmation(PVP in 4 cases,TURP in 1 case),2 patients re-ceived anti-tuberculosis therapy,and 3 cases were given antibiotics.Average follow-up was(20.6±11.2)months,and the average tPSA were(6.94±4.96)μg/L at 3-6 months after biopsy and/or surgery,with no obvious signs of malignancy during the follow-up period.Conclusion GP is the great mimicker of prostate cancer clinically and radiologically.Pros-tate biopsy is the method for confirming the diagnosis.For patients who are considering biopsy-free radical prostatectomy,it is important to consider the possibility of GP.

Congenital portosystemic shunts（CPSS）are vascular malformations caused by developmental anomalies that create abnormal shunts between the portal and systemic veins.This anomaly permits partial or complete bypass of portal blood flow from the liver，leading it directly into the systemic circulation without hepatic filtration.If untreated，CPSS can lead to multisystem complications，with pulmonary vascular complications being the most severe outcome.These complications are complex in mechanism，often insidious in onset，and present with nonspecific symptoms，increasing the risk of delayed diagnosis and significantly impacting the quality of children lives.Pulmonary vascular complications associated with CPSS primarily include portopulmonary hypertension，characterized by pulmonary vascular remodeling，and hepatopulmonary syndrome，distinguished by intrapulmonary vascular dilatation and abnormal arterial oxygenation.This article aims to review the anatomical classifications of CPSS，along with the pathophysiology，clinical presentation，diagnosis，and treatment of its pulmonary vascular complications，with the goal of enhancing clinical awareness and providing a reference for diagnosis and management.

Objective:To explore the role of chemokine CX3CL1/CX3CR1 in intraperitoneal metastasis of ovarian cancer in nude mice.Methods:Fifty SPF SD female nude mice were selected and randomly divided into normal group ( n=10) , ovarian cancer model group ( n=20) and CX3CL1 group ( n=20) by random number table method. Ovarian cancer model was not established in normal group, and ovarian cancer model was established in both ovarian cancer model group and CX3CL1 group. CX3CL1 group was given intraperitoneal injection of 20 μl CX3CL1 with a concentration of 10 ng/μl to observe the survival status of nude mice. Tumor mass, tumor volume, tumor inhibition rate, ascites rate and peritoneal metastasis rate were recorded. The pathological morphology of ovarian tissue was examined by HE staining, the expression of CX3CL1/CX3CR1 in ovarian tissue was detected by Western blotting, and the correlation between the expression of CX3CL1/CX3CR1 and peritoneal metastasis rate was analyzed by point two-column correlation. Results:During the administration, the mental state, activity, food and water intake of nude mice in the normal group were good with sensitive responses. The nude mice in the ovarian cancer model group showed signs of mental fatigue, reduced activity, less food and water intake, delayed response, as well as and a hard and gradually enlarged abdomen. The mental state, activity, food and water intake of nude mice in CX3CL1 group were better than those in ovarian cancer model group, and the abdominal hardness volume was smaller compared with that in ovarian cancer model group. The survival time of normal group, ovarian cancer model group and CX3CL1 group were (14.00±0.00) , (9.24±0.67) and (12.05±0.82) d, respectively, with a statistically significant difference ( F=22.27, P<0.001) . Further pair-to-pair comparisons showed that the normal group had the longest survival time, followed by the CX3CL1 group and the ovarian cancer model group (all P<0.05) . The tumor mass of ovarian cancer model group and CX3CL1 group was (1.31±0.21) and (0.62±0.13) g, respectively, with a statistically significant difference ( t=12.49, P<0.001) . The tumor volumes were (130.47±13.45) and (70.02±7.52) mm 3, respectively, with a statistically significant difference ( t=17.54, P<0.001) . The tumor suppression rates were (0.00±0.00) % and (48.96±4.74) %, respectively, with a statistically significant difference ( t=46.19, P<0.001) , the ascites rates were 60.00% (12/20) and 25.00% (5/20) , respectively, with a statistically significant difference ( χ2=5.01, P=0.025) . The abdominal metastasis rates were 80.00% (16/20) and 50.00% (10/20) , respectively, with a statistically significant difference ( χ2=3.96, P=0.047) . The results of HE staining showed that in the normal group, the ovarian tissue structure was complete, the follicles and oocytes developed normally with good shape, and no cancerous cells were found. The ovarian structure of the ovarian cancer model group was obviously destroyed, and a large number of cancerous cells could be seen. The nucleolus were deeply stained and the number increased. Compared with the ovarian cancer model group, the pathological structure was significantly improved, and the number of cancer cells was significantly decreased in the CX3CL1 group. The CX3CL1 protein relative expression levels in normal group, ovarian cancer model group and CX3CL1 group were 2.05±0.22, 1.33±0.11 and 2.41±0.24, respectively, with a statistically significant difference ( F=9.26, P<0.001) . The CX3CR1 protein relative expression levels were 1.99±0.21, 1.34±0.14, 2.73±0.31, respectively, with a statistically significant difference ( F=8.14, P<0.001) . Further pair-to-pair comparisons showed that compared with the normal group, the relative expression levels of CX3CL1 and CX3CR1 protein in ovarian cancer model group were significantly decreased, and the relative expression levels of CX3CL1 and CX3CR1 protein were higher in CX3CL1 group (all P<0.05) . Compared with ovarian cancer model group, the relative expression levels of CX3CL1 and CX3CR1 protein in ovarian tissue of CX3CL1 group were significantly increased (both P<0.05) . Correlation analysis showed that CX3CL1 and CX3CR1 expressions were negatively correlated with peritoneal metastasis rate ( r=-0.50, P=0.024; r=-0.58, P=0.012) . Conclusions:The expression of chemokine CX3CL1/CX3CR1 is down-regulated in ovarian cancer, and CX3CL1/CX3CR1 expression is negatively correlated with peritoneal metastasis of ovarian cancer. Activation of CX3CL1/CX3CR1 can significantly inhibit peritoneal metastasis of ovarian cancer.

Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.

Objective The aim of this study is to retrospectively analyze the clinical and imaging characteristics,treatment and prognosis of 13 patients with granulomatous prostatitis(GP),and to provide reference for the diagnosis and treatment for GP.Methods The clinical information of 13 GP patients extracted from electronic medical records including demographic characteristic risk factors,clinical symptoms,laboratory findings,imaging findings(ultrasound,CT,MRI,FDG-PET-CT),treatment and outcomes were analyzed retrospectively from January 2018 to August 2023 at our center.Results The average age of 13 patients with GP was(65.69±6.46)years.And the average score of IPSS was(23.40±5.8).Five patients appeared positive results,of which 11 cases received digital rectal examination.The average level of pre-biopsy tPSA was(23.28±44.94)μg/L with fPSA/tPSA ratio of 0.11±0.05 and PSAD of(0.55±1.07)μg/l/mL.The pre-biopsy mean MRI PI-RADS 2.0 was(4.6±0.6)in this group of patients.Extraprostatic invasion was shown on imaging in 4 patients.The average number of biopsy needles was(19.6±3.9),and the pathological results showed tuber-culous granulomas in 2 cases(15.4％)and non-specific granulomatous inflammation in 11 cases(84.6％).Five patients received local treatment of the prostate after pathological confirmation(PVP in 4 cases,TURP in 1 case),2 patients re-ceived anti-tuberculosis therapy,and 3 cases were given antibiotics.Average follow-up was(20.6±11.2)months,and the average tPSA were(6.94±4.96)μg/L at 3-6 months after biopsy and/or surgery,with no obvious signs of malignancy during the follow-up period.Conclusion GP is the great mimicker of prostate cancer clinically and radiologically.Pros-tate biopsy is the method for confirming the diagnosis.For patients who are considering biopsy-free radical prostatectomy,it is important to consider the possibility of GP.

AIM:To investigate the antiviral effica-cy and mechanism of Qingre Xiaoyanning(QRXYN)in vivo,and provide experimental basis for their prevention and treatment of influenza A virus.METHODS:We constructed a mouse model infect-ed with influenza A H3N2 virus.To evaluate the therapeutic effect of QRXYN on influenza A virus,we measured the body weight changes,pathologi-cal changes in lung tissue,hemagglutination titer,and viral load in mouse.To evaluate the possible mechanism of QRXYN's anti influenza A virus infec-tion,we used the ELISA to measure the levels of TNF-α,IL-1β,IL-4,IFN-γ,and vascular cell adhesion molecule-1(VCAM-1)in mouse bronchoalveolar Ia-vage fluid;used flow cytometry to assess the pro-portions of macrophages(F4/80),helper T lympho-cytes(CD4+T lymphocytes),and natural killer(NK)cells in lung tissue;and used Western blotting to detect the expression of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MYD88),inhibitor of kappa B kinase-β(IKK-β),NF-kappa-B inhibitor al-pha(IκBα),and phospho-IKB alpha(p-IκBα)in lung tissue.RESULTS:Compared to the model group,both Oseltamivir and QRXYN can alleviate the se-verity of lung tissue lesions in mice,decrease the blood coagulation titer and viral load of mouse lung tissue(P＜0.01),lower the levels of TNF-α,IL-4,and VCAM-1 in bronchoalveolar lavage fluid(P＜0.05,P＜0.01),reduce the proportion of macro-phages(P＜0.05,P＜0.01),and increase the propor-tion of CD4+T lymphocytes and NK cells(P＜0.05,P＜0.01).Additionally,oseltamivir can reduce the ex-pression of MYD88 protein in mouse lungs(P＜0.05),while QRXYN can decrease the expression of IKK-β and P-IκBα proteins in mouse lungs(P＜0.05).CONCLUSION:QRXYN have good in vivo antiviral ef-fects against the influenza A virus,and their mecha-nism may be related to the regulation of the immu-nologic function and NF-κB signal pathway.