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 establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

Objective To explore the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound,construct a nomogram for predicting poor postoperative prognosis,and conduct external validation of the nomogram.Methods Clinical data of 451 patients with intestinal obstruction who underwent endoscopic ultrasound transnasal-intestinal obstruction catheterization from February 2019 to February 2022 were collected to establish a nomogram.Then,194 sets of data with the same conditions from February 2022 to February 2024 were collected as the external validation group to validate the model externally.The recovery at 30 d after operation was observed and divided into good prognosis group and poor prognosis group.Multivariate Logistic regression model was used to analyze the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound.Using R 3.6.3 software and the RMS package,a nomogram model for predicting the risk of poor prognosis after intestinal obstruction catheterization under endoscopic ultrasound was constructed..The discrimination and consistency of the model were evaluated using receiver operator characteristic curve(ROC curve)and calibration curve.Results The patients in the poor prognosis group were older than those in the good prognosis group,the levels of C-reactive protein(CRP),procalcitonin(PCT)and neutrophil to lymphocyte ratio(NLR)were higher than those in the good prognosis group,the length of hospital stay was longer than that in the good prognosis group,and the proportion of diabetes,abdominal pain and hormone using were higher than those in the good prognosis group,body mass index(BMI),preoperative albumin level and preoperative nutritional support ratio were lower than those of the good prognosis group,with statistical significance(P<0.05).Multivariate Logistic regression analysis(introduction level was 0.05,exclusion level was 0.107)showed that:age≥68 years(OR＾=2.631,95%CI:1.927～3.593),BMI<22.31 kg/m2(OR＾=2.142,95%CI:1.436～3.195),preoperative albumin<32.47g/L(OR＾=1.962,95%CI:1.506～2.556)and preoperative nutritional non-support(OR＾=2.814,95%CI:1.401～5.654)were independent risk factors affecting the poor prognosis after endoscopic transnasal-intestinal obstruction catheterization(P<0.05).The column nomogram showed that old age,low BMI,low preoperative albumin,and no preoperative nutritional support all increased their corresponding weights.Internal and external validation results indicated good consistency and discrimination of the model.Conclusion age≥68 years,BMI<22.31 kg/m2,preoperative albumin<32.47 g/L,and no preoperative nutritional support are all independent risk factors affecting the ineffective of intestinal obstruction catheterization under endoscopic ultrasound.The nomogram model established in this study based on these four factors has high reliability and practicality.

Objective To explore the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound,construct a nomogram for predicting poor postoperative prognosis,and conduct external validation of the nomogram.Methods Clinical data of 451 patients with intestinal obstruction who underwent endoscopic ultrasound transnasal-intestinal obstruction catheterization from February 2019 to February 2022 were collected to establish a nomogram.Then,194 sets of data with the same conditions from February 2022 to February 2024 were collected as the external validation group to validate the model externally.The recovery at 30 d after operation was observed and divided into good prognosis group and poor prognosis group.Multivariate Logistic regression model was used to analyze the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound.Using R 3.6.3 software and the RMS package,a nomogram model for predicting the risk of poor prognosis after intestinal obstruction catheterization under endoscopic ultrasound was constructed..The discrimination and consistency of the model were evaluated using receiver operator characteristic curve(ROC curve)and calibration curve.Results The patients in the poor prognosis group were older than those in the good prognosis group,the levels of C-reactive protein(CRP),procalcitonin(PCT)and neutrophil to lymphocyte ratio(NLR)were higher than those in the good prognosis group,the length of hospital stay was longer than that in the good prognosis group,and the proportion of diabetes,abdominal pain and hormone using were higher than those in the good prognosis group,body mass index(BMI),preoperative albumin level and preoperative nutritional support ratio were lower than those of the good prognosis group,with statistical significance(P<0.05).Multivariate Logistic regression analysis(introduction level was 0.05,exclusion level was 0.107)showed that:age≥68 years(OR＾=2.631,95%CI:1.927～3.593),BMI<22.31 kg/m2(OR＾=2.142,95%CI:1.436～3.195),preoperative albumin<32.47g/L(OR＾=1.962,95%CI:1.506～2.556)and preoperative nutritional non-support(OR＾=2.814,95%CI:1.401～5.654)were independent risk factors affecting the poor prognosis after endoscopic transnasal-intestinal obstruction catheterization(P<0.05).The column nomogram showed that old age,low BMI,low preoperative albumin,and no preoperative nutritional support all increased their corresponding weights.Internal and external validation results indicated good consistency and discrimination of the model.Conclusion age≥68 years,BMI<22.31 kg/m2,preoperative albumin<32.47 g/L,and no preoperative nutritional support are all independent risk factors affecting the ineffective of intestinal obstruction catheterization under endoscopic ultrasound.The nomogram model established in this study based on these four factors has high reliability and practicality.

Objective:To establish 30-day of age transcutaneous bilirubin (TcB) reference curves for healthy neonates, and to investigate regional variations in bilirubin dynamics.Methods:A multicenter retrospective cohort study was conducted. A total of 220 950 healthy neonates born at a gestational age of 35-<42 weeks, with a birth weight ≥2 000 g, who did not receive phototherapy within 60 h after birth were recruited. All of them underwent remote TcB monitoring using the Bilibaby remote jaundice monitoring system between August 1 st, 2020 and December 31 st, 2024 in 426 hospitals. TcB data were collected within the period from birth to 30-day of age. The P40, P75, and P95 of TcB values were calculated, and dynamic TcB curves for 30-day of age were constructed. Patterns of bilirubin change, rates of change, and transition outcomes were described. Regional comparisons between South and North were conducted using linear mixed-effects models for TcB trajectories and Pearson′s chi-square test for outcome differences. Results:A total of 220 950 neonates were included, of whom 101 711 (46.03%) were female. Gestational age at birth was (38.75±1.12) weeks, and birth weight was (3 272±417) g. TcB levels increased rapidly within 3-day of age, peaked at 4-6-day of age, with peak values at P40, P75, and P95 of 200.6, 239.7 and 275.4 μmol/L (11.8, 14.1 and 16.2 mg/dl), respectively. TcB levels gradually declined thereafter and stabilized after 13-day of age, with values at P40, P75, and P95 fluctuating between 147.9-159.8, 190.4-200.6, and 231.2-239.7 μmol/L (8.7-9.4, 11.2-11.8, 13.6-14.1 mg/dl), respectively. Notably, among neonates categorized as low-or low-intermediate-risk within 3-day of age, 6 700 (12.76%) progressed to intermediate-high or high risk between 4 and 30 days of age. Before 13-day of age, TcB levels in the southern regions were consistently higher than those in the northern regions ( P=0.039); from 14 to 30 days of age, the overall TcB levels had no statistically difference, but the temporal changes in TcB still showed regional differences (degrees of freedom=3, all interaction P<0.05). Among neonates classified as low-or low-intermediate risk within 3-day of age, 25 326 were from southern regions, of whom 4 254 (16.80%) progressed to intermediate-high or high risk between 4 and 30 days of age. In northern regions, 27 193 neonates were classified as low-or low-intermediate risk within 3-day of age, among whom 2 446 (8.99%) progressed to intermediate-high or high risk. The risk progression between the 2 regions had statistically difference ( χ2=716.49, P<0.001). Conclusions:A TcB percentile curve for neonates within 30-day of age was established, revealing that both the overall TcB level and its temporal trend were higher in southern than in northern newborns. These findings provide baseline data to support continuous management of neonatal jaundice.

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside Ⅰ, gymnoside Ⅱ, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1β, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.
Animals ; Mice ; Stomach Ulcer/drug therapy* ; Proto-Oncogene Proteins c-akt ; Animal Experimentation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Vascular Endothelial Growth Factor A ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology*

The neonatal critical illness scoring system is widely used to assess the severity of neonatal disease, serious complications, neonatal mortality risk, long-term prognosis, and guide transport.At present, the scores widely used at home and abroad include clinical risk index for babies(CRIB), clinical risk index for babies Ⅱ(CRIB-Ⅱ), score for neonatal acute physiology(SNAP), score for neonatal acute physiology Ⅱ(SNAP-Ⅱ), score for neonatal acute physiology, perinatal extension, version Ⅱ(SNAPPE-Ⅱ), and neonatal critical illness score(NCIS), etc.Although there are many neonatal critical illness scoring systems, there is no recognized and ideal score, the most suitable score for assessing the severity of neonatal disease.This paper reviews the application and research progress of the three scoring systems SNAP-Ⅱ, SNAPPE-Ⅱ and NCIS.

Neonatal critical illness score(NCIS) has been published for over 20 years in China and has played an active role in critical neonatal transport, illness severity assessment, and prognosis evaluation.However, there are still some limitations in the scoring system with the development of medical technology, such as failure to include crucial perinatal information, unable to quantify single indicators, difficulty in obtaining PaO 2 without oxygen inhalation, complex evaluation indicators, long evaluation time and data was difficult for scientific research, etc.Therefore, it is necessary to update and simplify it for the clinical treatment and scientific study of critically ill newborns.This review summarized NCIS application in China and compared it with foreign neonatal critical scores such as score for neonatal acute physiology, clinical risk index for babies, etc.Combined with the rising technology of artificial intelligence and deep learning in recent years, it was more straightforward and optimized to enhance its accuracy and applicability, which was aimed to play a more active role in the treatment of critical newborns and scientific research.