Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To explore the factors affecting the enhancement quality of head and neck computed tomography angiography(CTA)images based on bolus-tracking technology,and provide a basis for quantitatively controlling image quality.Methods The general information,injection parameters,scanning parameters and analysis data of enhancement quality of images of 500 subjects who underwent head and neck CTA examinations in our hospital from January to June 2024 were prospectively collected.A comprehensive evaluation of enhancement quality of head and neck CTA images of the examinees was conducted,and the relevant examination data of the examinees with qualified and unqualified enhancement quality of images were compared.Multivariate Logistic regression analysis was used to analyze the independent factors influencing the enhancement quality of image.Results Among 500 CTA images of head and neck,262 cases had qualified enhancement quality of images and 238 cases were unqualified.There were statistically significant differences in gender,height,body weight,tube voltage,scanning direction,trigger threshold,diagnostic delay time,iodine contrast agent concentration,iodine contrast agent dosage,and iodine contrast agent flow rate between the examinees with qualified and unqualified enhancement quality of images(P<0.05).Multivariate Logistic analysis showed that the examinees were male(95%CI:0.22 to 0.75,P=0.004),body weight(95%CI:0.92 to 0.97,P<0.01),and head-foot direction scanning(95%CI:0.03 to 0.43,P=0.002),diagnostic delay time(95%CI:0.44 to 0.92,P=0.017),iodine contrast agent dosage(95%CI:1.21 to 1.34,P<0.001),iodine contrast agent flow rate(95%CI:0.14 to 0.59,P<0.001)were all the independent influencing factors of enhancement quality of image;Among them,the iodine contrast agent dosage(β=0.24,OR=1.27)was positively correlated with the enhancement quality of image,the examinees were male(β=-0.89,OR=0.41),body weight(β=-0.06,OR=0.94),head-foot direction scanning(β=-2.23,OR=0.11),diagnostic delay time(β=-0.45,OR=0.64),and iodine contrast agent flow rate(β=-1.26,OR=0.28)were negatively correlated with the enhancement quality of image.Conclusion In the application of bolus-tracking technology for head and neck CTA,individual factors,scanning parameters,and injection regimens are the key control elements that affect the positive results of enhancement quality of head and neck CTA images.In clinical practice,technicians can establish personalized scanning protocols by integrating artificial intelligence-assisted decision-making systems to achieve precise,standardized and personalized imaging.

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

Objective To explore the mechanism of electroacupuncture in alleviating hyperlipidemia in a rat model by modulating mammalian target of rapamycin complex 1(mTORC1)-mediated lipophagy in hepatocytes.Methods A total of 30 SD rats were randomly divided into blank(n=6)and modeling groups(n=24)using the random number table method.A hyperlipidemic rat model was established by feeding rats a high-fat diet(feeding for 8 weeks).After successful modeling,the modeling group was randomly divided into the model,electroacupuncture,mTORC1 inhibitor,and electroacupuncture+mTORC1 agonist groups,with six rats in each group.Except for the blank group,all other rats were fed with high fat diet.Rats in the electroacupuncture and electroacupuncture+mTORC1 agonist groups received electroacupuncture intervention at bilateral"Fenglong"(ST40)acupoints(dilatational wave 2 Hz/100 Hz,current intensity 1 mA)for 30 min once daily.Rats in the mTORC1 inhibitor group received intraperitoneal injections of the mTORC1 inhibitor,rapamycin(2 mg/kg),once daily.Rats in the electroacupuncture+mTORC1 agonist group received intraperitoneal injections of the mTORC1 agonist MHY1485(10 mg/kg)once daily.The interventions were administered for five consecutive days per week for 4 weeks.Upon completion of the intervention,the following analyses were performed:serum contents of total cholesterol(TC),triglycerides(TAG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured using a fully automated biochemical analyzer.Hepatic histopathological changes and lipid deposition were observed using hematoxylin-eosin and oil red O staining.The liver condition was observed and the liver index was calculated.Hepatic TC and TAG levels were measured using an enzyme-linked immunosorbent assay.The ultrastructure of the liver tissue was observed using transmission electron microscopy,and the mean fluorescence intensity of perilipin 2(PLIN2)and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ in the liver tissue was detected using immunofluorescence.Protein expression of LC3-Ⅱ/LC3-Ⅰ,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and mTORC1 in liver tissue was detected using Western blotting.Results Compared to the blank group,the model group rats showed increased serum TC,TAG,LDL-C,ALT,AST,and FFA levels,along with decreased HDL-C levels(P<0.05).The liver index and hepatic TC and TAG levels were also elevated(P<0.05).Histological examination of liver tissue revealed substantial lipid accumulation,numerous lipid droplets within hepatocytes,abnormal mitochondrial morphology,and scarce autophagic vacuole.The mean fluorescence intensity of PLIN2 increased,whereas that of LC3-Ⅱ decreased(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio was reduced,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression were increased(P<0.05).Compared to the model group,rats in the mTORC1 inhibitor and electroacupuncture groups exhibited decreased serum TC,TAG,LDL-C,ALT,AST,and FFA levels(P<0.05),along with a reduced liver index and hepatic TC and TAG levels(P<0.05).Histological examination showed markedly attenuated lipid accumulation and visible autophagic vacuole in the hepatocytes.The mean fluorescence intensity of PLIN2 decreased,whereas that of LC3-Ⅱ increased(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio increased,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression decreased(P<0.05).In comparison with both the electroacupuncture and mTORC1 inhibitor groups,the electroacupuncture+mTORC1 agonist group demonstrated increased serum TAG,TC,LDL-C,ALT,AST,and FFA levels(P<0.05)as well as elevated liver index and hepatic TC and TAG levels(P<0.05).Liver tissues exhibited aggravated lipid deposition and absence of autophagic vacuole in liver cells.The mean fluorescence intensity of PLIN2 was enhanced,whereas that of LC3-Ⅱ was reduced(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio decreased,and the p-mTOR/mTOR ratio and mTORC1 protein expression increased(P<0.05).Conclusion Electroacupuncture at"Fenglong"(ST40)may improve blood lipid levels in hyperlipidemic rats by inhibiting mTORC1 and promoting hepatocyte lipophagy.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of hepatitis E in Zhejiang Province from 2008 to 2023 and provide scientific evidence for the prevention and control of hepatitis E.Methods:The incidence data of hepatitis E in Zhejiang from 2008 to 2023 were obtained from China Disease Control and Prevention Information System. Joinpoint regression model was used to analyze the trends in incidence rates. Software ArcGIS 10.8 was used to analyze the spatial distribution and autocorrelation of hepatitis E cases, while software SaTScan 10.1 was used to investigate spatial clustering at district level.Results:A total of 33 027 cases of hepatitis E were reported in Zhejiang from 2008 to 2023. The average annual incidence rate was 3.64/100 000. The majority of the cases reported were men (21 739), and higher average annual incidence rate was observed in the age group 50-74 years (32.04/100 000). The overall reported incidence rate declined first and then increased in 2020, showing a seasonal distribution with a high incidence from January to May. Notably, the incidence was particularly high in Hangzhou (6.54/100 000) and Quzhou (5.56/100 000). Spatial autocorrelation analyses revealed that the incidence of hepatitis E exhibited high-high clustering in all the years, with northwestern Zhejiang as main affected area. Prior to 2020, the high-high clustering area in northwestern Zhejiang became smaller, followed by an expansion trend in 2020-2022. Spatiotemporal clustering analyses identified seven clustering areas from 2010 to 2019, one was in 16 counties (cities, districts) in northwestern Zhejiang. And the clustering areas along the coastline shifted from the north to the south.Conclusions:The incidence of hepatitis E in Zhejiang exhibited distinct spatiotemporal clustering pattern. Consequently, targeted prevention and control measures could be taken for hepatitis E in high-risk areas in Zhejiang, including northwestern and coastal areas.

Objective To explore the mechanism of electroacupuncture in alleviating hyperlipidemia in a rat model by modulating mammalian target of rapamycin complex 1(mTORC1)-mediated lipophagy in hepatocytes.Methods A total of 30 SD rats were randomly divided into blank(n=6)and modeling groups(n=24)using the random number table method.A hyperlipidemic rat model was established by feeding rats a high-fat diet(feeding for 8 weeks).After successful modeling,the modeling group was randomly divided into the model,electroacupuncture,mTORC1 inhibitor,and electroacupuncture+mTORC1 agonist groups,with six rats in each group.Except for the blank group,all other rats were fed with high fat diet.Rats in the electroacupuncture and electroacupuncture+mTORC1 agonist groups received electroacupuncture intervention at bilateral"Fenglong"(ST40)acupoints(dilatational wave 2 Hz/100 Hz,current intensity 1 mA)for 30 min once daily.Rats in the mTORC1 inhibitor group received intraperitoneal injections of the mTORC1 inhibitor,rapamycin(2 mg/kg),once daily.Rats in the electroacupuncture+mTORC1 agonist group received intraperitoneal injections of the mTORC1 agonist MHY1485(10 mg/kg)once daily.The interventions were administered for five consecutive days per week for 4 weeks.Upon completion of the intervention,the following analyses were performed:serum contents of total cholesterol(TC),triglycerides(TAG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured using a fully automated biochemical analyzer.Hepatic histopathological changes and lipid deposition were observed using hematoxylin-eosin and oil red O staining.The liver condition was observed and the liver index was calculated.Hepatic TC and TAG levels were measured using an enzyme-linked immunosorbent assay.The ultrastructure of the liver tissue was observed using transmission electron microscopy,and the mean fluorescence intensity of perilipin 2(PLIN2)and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ in the liver tissue was detected using immunofluorescence.Protein expression of LC3-Ⅱ/LC3-Ⅰ,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and mTORC1 in liver tissue was detected using Western blotting.Results Compared to the blank group,the model group rats showed increased serum TC,TAG,LDL-C,ALT,AST,and FFA levels,along with decreased HDL-C levels(P<0.05).The liver index and hepatic TC and TAG levels were also elevated(P<0.05).Histological examination of liver tissue revealed substantial lipid accumulation,numerous lipid droplets within hepatocytes,abnormal mitochondrial morphology,and scarce autophagic vacuole.The mean fluorescence intensity of PLIN2 increased,whereas that of LC3-Ⅱ decreased(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio was reduced,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression were increased(P<0.05).Compared to the model group,rats in the mTORC1 inhibitor and electroacupuncture groups exhibited decreased serum TC,TAG,LDL-C,ALT,AST,and FFA levels(P<0.05),along with a reduced liver index and hepatic TC and TAG levels(P<0.05).Histological examination showed markedly attenuated lipid accumulation and visible autophagic vacuole in the hepatocytes.The mean fluorescence intensity of PLIN2 decreased,whereas that of LC3-Ⅱ increased(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio increased,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression decreased(P<0.05).In comparison with both the electroacupuncture and mTORC1 inhibitor groups,the electroacupuncture+mTORC1 agonist group demonstrated increased serum TAG,TC,LDL-C,ALT,AST,and FFA levels(P<0.05)as well as elevated liver index and hepatic TC and TAG levels(P<0.05).Liver tissues exhibited aggravated lipid deposition and absence of autophagic vacuole in liver cells.The mean fluorescence intensity of PLIN2 was enhanced,whereas that of LC3-Ⅱ was reduced(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio decreased,and the p-mTOR/mTOR ratio and mTORC1 protein expression increased(P<0.05).Conclusion Electroacupuncture at"Fenglong"(ST40)may improve blood lipid levels in hyperlipidemic rats by inhibiting mTORC1 and promoting hepatocyte lipophagy.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To explore the factors affecting the enhancement quality of head and neck computed tomography angiography(CTA)images based on bolus-tracking technology,and provide a basis for quantitatively controlling image quality.Methods The general information,injection parameters,scanning parameters and analysis data of enhancement quality of images of 500 subjects who underwent head and neck CTA examinations in our hospital from January to June 2024 were prospectively collected.A comprehensive evaluation of enhancement quality of head and neck CTA images of the examinees was conducted,and the relevant examination data of the examinees with qualified and unqualified enhancement quality of images were compared.Multivariate Logistic regression analysis was used to analyze the independent factors influencing the enhancement quality of image.Results Among 500 CTA images of head and neck,262 cases had qualified enhancement quality of images and 238 cases were unqualified.There were statistically significant differences in gender,height,body weight,tube voltage,scanning direction,trigger threshold,diagnostic delay time,iodine contrast agent concentration,iodine contrast agent dosage,and iodine contrast agent flow rate between the examinees with qualified and unqualified enhancement quality of images(P<0.05).Multivariate Logistic analysis showed that the examinees were male(95%CI:0.22 to 0.75,P=0.004),body weight(95%CI:0.92 to 0.97,P<0.01),and head-foot direction scanning(95%CI:0.03 to 0.43,P=0.002),diagnostic delay time(95%CI:0.44 to 0.92,P=0.017),iodine contrast agent dosage(95%CI:1.21 to 1.34,P<0.001),iodine contrast agent flow rate(95%CI:0.14 to 0.59,P<0.001)were all the independent influencing factors of enhancement quality of image;Among them,the iodine contrast agent dosage(β=0.24,OR=1.27)was positively correlated with the enhancement quality of image,the examinees were male(β=-0.89,OR=0.41),body weight(β=-0.06,OR=0.94),head-foot direction scanning(β=-2.23,OR=0.11),diagnostic delay time(β=-0.45,OR=0.64),and iodine contrast agent flow rate(β=-1.26,OR=0.28)were negatively correlated with the enhancement quality of image.Conclusion In the application of bolus-tracking technology for head and neck CTA,individual factors,scanning parameters,and injection regimens are the key control elements that affect the positive results of enhancement quality of head and neck CTA images.In clinical practice,technicians can establish personalized scanning protocols by integrating artificial intelligence-assisted decision-making systems to achieve precise,standardized and personalized imaging.

Objective:To understand the epidemiological characteristics and spatiotemporal distribution of hepatitis E in Zhejiang Province from 2008 to 2023 and provide scientific evidence for the prevention and control of hepatitis E.Methods:The incidence data of hepatitis E in Zhejiang from 2008 to 2023 were obtained from China Disease Control and Prevention Information System. Joinpoint regression model was used to analyze the trends in incidence rates. Software ArcGIS 10.8 was used to analyze the spatial distribution and autocorrelation of hepatitis E cases, while software SaTScan 10.1 was used to investigate spatial clustering at district level.Results:A total of 33 027 cases of hepatitis E were reported in Zhejiang from 2008 to 2023. The average annual incidence rate was 3.64/100 000. The majority of the cases reported were men (21 739), and higher average annual incidence rate was observed in the age group 50-74 years (32.04/100 000). The overall reported incidence rate declined first and then increased in 2020, showing a seasonal distribution with a high incidence from January to May. Notably, the incidence was particularly high in Hangzhou (6.54/100 000) and Quzhou (5.56/100 000). Spatial autocorrelation analyses revealed that the incidence of hepatitis E exhibited high-high clustering in all the years, with northwestern Zhejiang as main affected area. Prior to 2020, the high-high clustering area in northwestern Zhejiang became smaller, followed by an expansion trend in 2020-2022. Spatiotemporal clustering analyses identified seven clustering areas from 2010 to 2019, one was in 16 counties (cities, districts) in northwestern Zhejiang. And the clustering areas along the coastline shifted from the north to the south.Conclusions:The incidence of hepatitis E in Zhejiang exhibited distinct spatiotemporal clustering pattern. Consequently, targeted prevention and control measures could be taken for hepatitis E in high-risk areas in Zhejiang, including northwestern and coastal areas.

Immune response occurs in a variety of cellular stresses that severely disrupt function of endoplasmic reticulum(ER),leading to accumulation of misfolded or unfolded protein in ER lumen,resulting in endoplasmic reticulum stress(ERS).ERS triggers unfolded protein response to restore ER homeostasis,but its duration is too long and can lead to cell apoptosis.Although sus-tained ERS can lead to an increase in pro-inflammatory cytokines that induce inflammatory responses and activate immune responses,causal relationship between ERS and immune responses has not been established.This review summarizes role of ERS in inducing im-mune cell differentiation,cytokine expression and immune function,and further illustrates regulatory role of ERS in pathogenesis of immune disorders,which is helpful to explore new therapies for ERS-related diseases.