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

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective:To use machine learning to predict the efficacy of accelerated corneal collagen cross-linking (A-CXL) surgery, identify prognostic factors, and construct models to predict postoperative disease progression.Methods:A single-center retrospective study was conducted.A total of 82 keratoconus patients (112 eyes) who underwent A-CXL surgery at the West China Hospital of Sichuan University between March and December 2021 were enrolled.Preoperative and follow-up examinations included anterior segment evaluation by slit-lamp microscopy, corneal topography using Pentacam, and corneal biomechanical indices using Corvis ST.Disease progression was defined as an increase in maximum keratometry (Kmax) of ≥1 D from the preoperative level at the last follow-up.Various machine learning algorithms were employed to analyze corneal topography, biomechanical parameters and corneal densitometry values to identify prognostic factors and construct models for predicting postoperative disease progression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (No.2023496).Written informed consent was obtained from each subject.Results:During follow-up, 15.1% (17/112) of the eyes showed progression after A-CXL.The preoperative astigmatism and stress-strain index (SSI) in the progression group were (-5.41±2.72)D and 1.41±0.78, respectively, which were significantly higher than (-3.30±2.54)D and 0.95±0.98 in the non-progression group ( t=2.80, 2.03; both P<0.05).Cox regression analysis identified preoperative astigmatism (hazard ratio [HR]=1.20), SSI (HR=1.10), and anterior corneal densitometry of 2-6 mm (CDA6) (HR=2.10) as significant risk factors for post-A-CXL progression.Among various machine learning models developed and validated, the area under the curve (AUC) values for logistic regression, multilayer perceptron (MLP) model, and random forest (RF) exceeded 0.700.For F1-score, the AUC values for logistic regression, MLP, and RF were 0.870, 0.880, and 0.880, respectively.The network structure of the visualized MLP was a single-layer, 24-neurons neural network with 80% accuracy in predicting whether progression occurred after A-CXL.The clinical nomogram developed in conjunction with astigmatism, SSI, and CDA6 predicted the cumulative probability of progression at 0.5, 1, and 2 years postoperatively based on the sum of the specified values for each variable, and based on the optimal cutoff value, keratoconus corneas could be classified into high-, intermediate-, and low-risk groups, respectively.The time-dependent subject operating characteristic curves of the nomogram showed AUCs of 0.734, 0.685, and 0.935 at 0.5, 1, and 2 years postoperatively, respectively, all of which performed well in predicting progression. Conclusions:Preoperative astigmatism, SSI, and CDA6 are significant risk factors for post-A-CXL progression in keratoconus.The MLP model can accurately predict postoperative disease progression, and the clinical nomogram combining preoperative astigmatism, SSI, and CDA6 can effectively differentiate between low-, medium-, and high-risk postoperative progression outcomes.

Objective:To investigate whether malignant tumors affect the laboratory outcomes of patients in their first controlled ovarian hyperstimulation (COH) cycle.Methods:This study was a retrospective case-control study that analyzed the clinical and laboratory data of patients who underwent fertility preservation before chemotherapy and radiotherapy due to malignant tumors, as well as patients with infertility caused by tubal factors who first underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2020 to May 2024. Patients who underwent fertility preservation were designated as the research group, while patients who underwent assisted reproduction due to tubal factors during the same period were designated as control group. After 1∶3 propensity score matching (PSM), 40 patients were included in the research group and 118 patients were included in control group. The ovarian response, oocyte retrieval outcomes, and embryonic development after fertilization in the first COH cycle were compared between the two groups. Results:After PSM, the research group and control group showed statistically significant differences in the gonadotropin (Gn) starting dosage [225.00 (162.50, 300.00) U vs. 193.75 (150.00, 225.00) U, P=0.002], duration of Gn used [10.00 (8.00, 11.00) d vs. 12.00 (10.00, 13.00) d, P<0.001], and average estradiol levels on human chorionic gonadotropin trigger day [2 487.00 (1 461.25, 4 090.25) pmol/L vs. 10 738.50 (8 400.00, 16 507.25) pmol/L, P<0.001]. However, no statistically significant difference was found in the total dosages of Gn used between the two groups ( P>0.05). There were no significant differences between the groups in terms of the number of oocytes retrieved, the number of metaphase Ⅱ oocytes, two pronuclei (2PN) rate, 2PN cleavage rate, available embryo rate, high-quality embryo rate, blastocyst formation rate, and available blastocyst formation rate (all P>0.05). Conclusion:Compared with infertility patients with tubal factors, there is no significant difference in the laboratory outcomes of malignant tumor patients undergoing COH for fertility preservation prior to chemotherapy and radiation.

Objective:To investigate whether malignant tumors affect the laboratory outcomes of patients in their first controlled ovarian hyperstimulation (COH) cycle.Methods:This study was a retrospective case-control study that analyzed the clinical and laboratory data of patients who underwent fertility preservation before chemotherapy and radiotherapy due to malignant tumors, as well as patients with infertility caused by tubal factors who first underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2020 to May 2024. Patients who underwent fertility preservation were designated as the research group, while patients who underwent assisted reproduction due to tubal factors during the same period were designated as control group. After 1∶3 propensity score matching (PSM), 40 patients were included in the research group and 118 patients were included in control group. The ovarian response, oocyte retrieval outcomes, and embryonic development after fertilization in the first COH cycle were compared between the two groups. Results:After PSM, the research group and control group showed statistically significant differences in the gonadotropin (Gn) starting dosage [225.00 (162.50, 300.00) U vs. 193.75 (150.00, 225.00) U, P=0.002], duration of Gn used [10.00 (8.00, 11.00) d vs. 12.00 (10.00, 13.00) d, P<0.001], and average estradiol levels on human chorionic gonadotropin trigger day [2 487.00 (1 461.25, 4 090.25) pmol/L vs. 10 738.50 (8 400.00, 16 507.25) pmol/L, P<0.001]. However, no statistically significant difference was found in the total dosages of Gn used between the two groups ( P>0.05). There were no significant differences between the groups in terms of the number of oocytes retrieved, the number of metaphase Ⅱ oocytes, two pronuclei (2PN) rate, 2PN cleavage rate, available embryo rate, high-quality embryo rate, blastocyst formation rate, and available blastocyst formation rate (all P>0.05). Conclusion:Compared with infertility patients with tubal factors, there is no significant difference in the laboratory outcomes of malignant tumor patients undergoing COH for fertility preservation prior to chemotherapy and radiation.

Objective:To use machine learning to predict the efficacy of accelerated corneal collagen cross-linking (A-CXL) surgery, identify prognostic factors, and construct models to predict postoperative disease progression.Methods:A single-center retrospective study was conducted.A total of 82 keratoconus patients (112 eyes) who underwent A-CXL surgery at the West China Hospital of Sichuan University between March and December 2021 were enrolled.Preoperative and follow-up examinations included anterior segment evaluation by slit-lamp microscopy, corneal topography using Pentacam, and corneal biomechanical indices using Corvis ST.Disease progression was defined as an increase in maximum keratometry (Kmax) of ≥1 D from the preoperative level at the last follow-up.Various machine learning algorithms were employed to analyze corneal topography, biomechanical parameters and corneal densitometry values to identify prognostic factors and construct models for predicting postoperative disease progression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (No.2023496).Written informed consent was obtained from each subject.Results:During follow-up, 15.1% (17/112) of the eyes showed progression after A-CXL.The preoperative astigmatism and stress-strain index (SSI) in the progression group were (-5.41±2.72)D and 1.41±0.78, respectively, which were significantly higher than (-3.30±2.54)D and 0.95±0.98 in the non-progression group ( t=2.80, 2.03; both P<0.05).Cox regression analysis identified preoperative astigmatism (hazard ratio [HR]=1.20), SSI (HR=1.10), and anterior corneal densitometry of 2-6 mm (CDA6) (HR=2.10) as significant risk factors for post-A-CXL progression.Among various machine learning models developed and validated, the area under the curve (AUC) values for logistic regression, multilayer perceptron (MLP) model, and random forest (RF) exceeded 0.700.For F1-score, the AUC values for logistic regression, MLP, and RF were 0.870, 0.880, and 0.880, respectively.The network structure of the visualized MLP was a single-layer, 24-neurons neural network with 80% accuracy in predicting whether progression occurred after A-CXL.The clinical nomogram developed in conjunction with astigmatism, SSI, and CDA6 predicted the cumulative probability of progression at 0.5, 1, and 2 years postoperatively based on the sum of the specified values for each variable, and based on the optimal cutoff value, keratoconus corneas could be classified into high-, intermediate-, and low-risk groups, respectively.The time-dependent subject operating characteristic curves of the nomogram showed AUCs of 0.734, 0.685, and 0.935 at 0.5, 1, and 2 years postoperatively, respectively, all of which performed well in predicting progression. Conclusions:Preoperative astigmatism, SSI, and CDA6 are significant risk factors for post-A-CXL progression in keratoconus.The MLP model can accurately predict postoperative disease progression, and the clinical nomogram combining preoperative astigmatism, SSI, and CDA6 can effectively differentiate between low-, medium-, and high-risk postoperative progression outcomes.

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.