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 analyze the correlation between right atrial strain at various stages and various influencing factors in patients with pulmonary hypertension,and to explore the role of right atrial strain in the assessment of pulmonary hypertension.Methods A total of 239 cases diagnosed with pulmonary hypertension who underwent echocardiography and complete right heart catheterization at hospital from October 2021 to December 2023 were included.Conventional ultrasound parameters such as right heart strain,right atrial area(RA area),inferior vena cava diameter(IVC diameter),and collapse rate of the inferior vena cava(IVC diameter changes)were measured.The heart rate(HR)corresponding to the ultrasound images were recorded.General information such as age and gender,as well as catheter data including mean right atrial pressure(mRAP),mean pulmonary artery pressure(mPAP),and pulmonary vascular resistance(PVR),were collected.The relationship between right atrial strain and its influencing factors was analyzed,and further analysis was conducted by dividing into shunt group and non-shunt group based on the presence or absence of left-to-right shunt disease.Results The correlation with RA reservoir strain(RASr)from high to low is RV global strain(RV4CSL),RV free wall strain(RVFWSL),RA area,IVC diameter,mRAP,age,HR,and PVR;the correlation with RAconduit strain(RAScd)from high to low is RV4CSL,RVFWSL,RA area,IVC diameter,mRAP,age,PVR,and HR;the correlation with RA contraction strain(RASct)from high to low is RA area,RV4CSL,RVFWSL,mRAP,IVC diameter,and HR.The collapse rate of the inferior vena cava is correlated with strain at various stages of the right atrium;gender is correlated with RASr and RASct.Conclusions Right atrial strain can reflect changes in right atrial function,with the highest correlation to right ventricular strain and right atrial area.Right atrial strain can indicate the severity of right ventricular function and right atrial remodeling,serving as an evaluative index for the condition and treatment outcomes of pulmonary arterial hypertension.

Objective:To explore the clinical efficacy of the splenic vessel-oriented anatomical plane priority strategy in Da Vinci robotic Kimura distal pancreatectomy.Methods:A retrospective analysis was conducted on 26 patients who underwent robotic-assisted distal pancreatectomy at Zhejiang Provincial People’s Hospital from January 2019 to September 2024. The cohort included 7 male and 19 female patients, aged (49.3±16.7) years. Surgical outcomes, including operative time, intraoperative blood loss, postoperative complications, and hospital stay, were analyzed, and surgical techniques were summarized.Results:All 26 patients successfully completed the surgery. Pathological diagnoses included 5 cases of intraductal papillary mucinous neoplasm, 5 serous cystadenomas, 1 pancreatic neuroendocrine tumor, 6 solid pseudopapillary neoplasms, 4 mucinous cystic neoplasms, and 5 neuroendocrine tumors. The maximum tumor diameter was (2.3±1.1) cm, and the operative time was (183.2±77.4) min. The spleen preservation rate was 100% (26/26). Intraoperative blood loss was 50.0 (17.5, 125) ml, and postoperative hospital stay was (10.1±3.7) d. No Clavien-Dindo grade III or higher complications occurred. The post-operative pancreatic fistula (POPF) rate was 53.8% (14/26), including 38.5% (10/26) biochemical leak and 15.3% (4/26) grade B POPF, with no grade C POPF.Conclusion:The splenic vessel-oriented anatomical plane priority strategy in robotic-assisted spleen-preserving distal pancreatectomy (Kimura technique) is safe and feasible, significantly improving the spleen preservation rate.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To evaluate the efficacy of loose-leaf textbooks in nursing risk education for nursing interns.Methods A random number table was used to divide 120 nursing interns in the geriatric oncology department into intervention and control groups,with 60 in each group.The control group received standard clinical nursing instruction,while the intervention group was taught using loose-leaf teaching materials in addition to standard clinical instruction.Occupational risk cognition,pa-tient safety perception,theoretical scores,clinical skills scores,and teaching satisfaction were compared between the two groups.Results The intervention group showed significantly higher scores in occupational risk cognition,patient safety perception,theo-retical achievement,clinical skills achievement,and teaching satisfaction compared to the control group(P＜0.05).Conclu-sion Loose-leaf textbooks enhance nursing interns' learning of occupational risks,improve patient safety perception,boost theo-retical and clinical skills performance,and increase teaching satisfaction.

Objective To analyze the correlation between right atrial strain at various stages and various influencing factors in patients with pulmonary hypertension,and to explore the role of right atrial strain in the assessment of pulmonary hypertension.Methods A total of 239 cases diagnosed with pulmonary hypertension who underwent echocardiography and complete right heart catheterization at hospital from October 2021 to December 2023 were included.Conventional ultrasound parameters such as right heart strain,right atrial area(RA area),inferior vena cava diameter(IVC diameter),and collapse rate of the inferior vena cava(IVC diameter changes)were measured.The heart rate(HR)corresponding to the ultrasound images were recorded.General information such as age and gender,as well as catheter data including mean right atrial pressure(mRAP),mean pulmonary artery pressure(mPAP),and pulmonary vascular resistance(PVR),were collected.The relationship between right atrial strain and its influencing factors was analyzed,and further analysis was conducted by dividing into shunt group and non-shunt group based on the presence or absence of left-to-right shunt disease.Results The correlation with RA reservoir strain(RASr)from high to low is RV global strain(RV4CSL),RV free wall strain(RVFWSL),RA area,IVC diameter,mRAP,age,HR,and PVR;the correlation with RAconduit strain(RAScd)from high to low is RV4CSL,RVFWSL,RA area,IVC diameter,mRAP,age,PVR,and HR;the correlation with RA contraction strain(RASct)from high to low is RA area,RV4CSL,RVFWSL,mRAP,IVC diameter,and HR.The collapse rate of the inferior vena cava is correlated with strain at various stages of the right atrium;gender is correlated with RASr and RASct.Conclusions Right atrial strain can reflect changes in right atrial function,with the highest correlation to right ventricular strain and right atrial area.Right atrial strain can indicate the severity of right ventricular function and right atrial remodeling,serving as an evaluative index for the condition and treatment outcomes of pulmonary arterial hypertension.

Objective To evaluate the efficacy of loose-leaf textbooks in nursing risk education for nursing interns.Methods A random number table was used to divide 120 nursing interns in the geriatric oncology department into intervention and control groups,with 60 in each group.The control group received standard clinical nursing instruction,while the intervention group was taught using loose-leaf teaching materials in addition to standard clinical instruction.Occupational risk cognition,pa-tient safety perception,theoretical scores,clinical skills scores,and teaching satisfaction were compared between the two groups.Results The intervention group showed significantly higher scores in occupational risk cognition,patient safety perception,theo-retical achievement,clinical skills achievement,and teaching satisfaction compared to the control group(P＜0.05).Conclu-sion Loose-leaf textbooks enhance nursing interns' learning of occupational risks,improve patient safety perception,boost theo-retical and clinical skills performance,and increase teaching satisfaction.

Objective:To explore the clinical efficacy of the splenic vessel-oriented anatomical plane priority strategy in Da Vinci robotic Kimura distal pancreatectomy.Methods:A retrospective analysis was conducted on 26 patients who underwent robotic-assisted distal pancreatectomy at Zhejiang Provincial People’s Hospital from January 2019 to September 2024. The cohort included 7 male and 19 female patients, aged (49.3±16.7) years. Surgical outcomes, including operative time, intraoperative blood loss, postoperative complications, and hospital stay, were analyzed, and surgical techniques were summarized.Results:All 26 patients successfully completed the surgery. Pathological diagnoses included 5 cases of intraductal papillary mucinous neoplasm, 5 serous cystadenomas, 1 pancreatic neuroendocrine tumor, 6 solid pseudopapillary neoplasms, 4 mucinous cystic neoplasms, and 5 neuroendocrine tumors. The maximum tumor diameter was (2.3±1.1) cm, and the operative time was (183.2±77.4) min. The spleen preservation rate was 100% (26/26). Intraoperative blood loss was 50.0 (17.5, 125) ml, and postoperative hospital stay was (10.1±3.7) d. No Clavien-Dindo grade III or higher complications occurred. The post-operative pancreatic fistula (POPF) rate was 53.8% (14/26), including 38.5% (10/26) biochemical leak and 15.3% (4/26) grade B POPF, with no grade C POPF.Conclusion:The splenic vessel-oriented anatomical plane priority strategy in robotic-assisted spleen-preserving distal pancreatectomy (Kimura technique) is safe and feasible, significantly improving the spleen preservation rate.

Objective A simple,sensitive and rapid ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for the determination of ertapenem in human plasma.Methods Using ertapenem-D4 as internal standard,the protein in plasma was precipitated with acetonitrile;chromatographic column:ACQUITY HSS T3(2.1 mm × 50.0 mm,1.8 μm);the mobile phase was 0.1％formic acid aqueous solution(containing 2 mmol·L-1 ammonium formate)-acetonitrile(0.1％formic acid),using a gradient elution;flow rate:0.4 mL·min-1,injection volume:1 μL,column temperature:45 ℃,the analysis time was 4.5 min,the scanning mode is positive ion selective reaction monitoring mode(SRM)with an electric spray ion source(ESI).The specificity,standard curve and lower limit of quantification,precision and recovery,matrix effect,dilution effect and stability were investigated.Results Ertapenem had a good linearity within 0.5-80.0μg·mL-1,and the standard curve was y=4.25 × 10-1x-2.64× 10-2(r2=0.999 0),the lower limit of quantification was 0.5 μg·mL-1,the relative standard deviation within and between batches is 1.39％-4.15％.The extraction recovery rate was 58.36％-64.57％,and the relative standard deviation of dilution effect was 3.30％,and the matrix effect was 99.71％-103.23％.The relative standard deviation of room temperature,repeated freeze-thaw,4 ℃,and long-term stability are all less than 10％.Conclusion The method is sensitive,rapid and specific,which is suitable for clinical monitoring of Ertapenem.

Objective:To explore the feasibility and effect of remote medical education model using online film reading training to improve the ability of ophthalmologists in the Xinjiang Uygur Autonomous Region (hereinafter referred to as "Xinjiang Region" ) in diagnosing fundus diseases.Methods:The three-level film reading training system of Xinjiang Production and Construction Corps system division hospital-Corps Hospital-Peking Union Medical College Hospital was established. From June 2022 to January 2023, 4 159 posterior color fundus images were continuously collected from Department of Ophthalmology of Xinjiang Corps Hospital and 4 divisional hospitals in the Corps medical system. Among them, hypertensive retinopathy, diabetic retinopathy, exudative age-related macular degeneration (AMD), atrophic AMD and retinal vein occlusion were 3 073, 651, 43, 186 and 206 cases, respectively. The images were divided into 3 rounds (first, second and last) according to the proportion of diseases. The doctors who participated in the training (hereinafter referred to as the "training") were 15 ophthalmologists from the Corps Hospital of Xinjiang Region and the division hospital of the Corps system. There were 7 male and 8 female. Age was (38.1±4.0) years. The titles of senior, deputy senior, intermediate and junior are 1, 6, 5 and 3 respectively; Bachelor's degree and master's degree are 13 and 2 respectively. The working time of fundus disease specialty was (9.6±3.3) years. The film reading system training was conducted before the first round of labeling, and after each round of film reading, the doctors of Peking Union Medical College Hospital gave feedback and explanation on the film reading results. The diagnostic consistency, sensitivity and specificity were compared by paired sample t test. Spearman or Pearson correlation analysis was conducted between the improvement of diagnostic level and professional title, education, age and working hours of ocular fundus disease. Results:All the participating doctors completed the first, second and last reading. After each round of film reading, the film reading summary was carried out for 2 hours. The average diagnostic agreement rates of participating physicians were 53.0%, 67.0% and 75.0%, respectively. The sensitivity and specificity were 0.38, 0.69, 054 and 0.66, 0.85, 0.96, respectively. There was significant difference between the first and last examination ( P<0.001). The sensitivity of the second reading was significantly higher than that of the first reading, and the sensitivity of the last reading was significantly lower than that of the second reading, with statistical significance ( P<0.05). The specificity of the second reading was significantly higher than that of the first reading, and the last reading was significantly higher than that of the second reading, with statistical significance ( P<0.05). There was no significant correlation ( P>0.05) between the improvement of diagnostic level of participating physicians and educational background ( Rho=0.07), professional title ( Rho=0.13), age ( r=0.20), and working time of ophthalmofundus disease specialty ( r=0.26). Conclusions:Relying on the three-level online telemedicine training, it can improve the ability of ophthalmologists in Xinjiang region to diagnose fundus diseases. The preliminary telemedicine education model has demonstrated potential for feasibility and effectiveness in remote areas with inadequate medical resources.