ObjectiveTo establish the self-reported core outcome set （COS） for patients with an example of a community study on heat-sensitive moxibustion for primary hypertension （PH）， to provide a reference for the selection of effectiveness evaluation indicators in community study on heat-sensitive moxibustion. MethodsA systematic literature search was conducted to collect outcomes used in randomized controlled trials and systematic review of heat-sensitive moxibustion for PH （Jan 2021）， and additional outcomes were added through patient and expert questionnaires （Feb 2021） to create a pool of outcome entries. A multidisciplinary expert Delphi survey was conducted to screen outcomes applicable to patient self-reporting （Apr 2021）， and the importance of outcome indicators was rated on a 5-Point Likert Scale. Finally， patient self-reported COS was determined through a consensus conference （June 2021）. ResultsA pool of patient self-reported indicators in the community study of heat-sensitive moxibustion treatment for PH was generated by standardizing and combining the outcome indicators based on the results of the literature search and the questionnaire survey， which consisted of totally 100 measurement tools or contents， excluding 51 indicators or measurement tools required measurement by specialized physicians or hospital equipment， and 49 items were retained to enter the initial list of indicator entries. For the first round of Delphi survey， the mean score for expert familiarity was 0.819， the mean score for basis of judgment was 0.710， and the expert authority coefficient was 0.765， with a total of 21 indicator measurement tools or contents deleted （significance score ≤ 75 or coefficient of variation ＞ 0.25）， 28 retained， and 3 new expert-added indicator entries added. In the second round of Delphi survey， the average score for expert familiarity was 0.859， the average score for basis for judgment was 0.763， and the expert authority coefficient was 0.811， with a total of 11 indicator measurement tools or contents deleted and 20 retained involving 5 domains. Following an expert consensus meeting， 8 outcome indicators were finalized for inclusion in the patient self-reported COS， including 6 indicators of effectiveness evaluation such as quality-of-life scores， blood pressure， traditional Chinese medicine symptom scores， cost-benefit， cardiovascular and cerebrovascular events， and adverse reactions/events， and 2 indicators of factors influencing effectiveness such as sensation of heat-sensitive moxibustion， and adherence. ConclusionIn this study， we initially established a criteria for evaluating the effectiveness in the community study on heat-sensitive moxibustion by constructing patient self-reported COS in the community study on heat-sensitive moxibustion for PH， which can provide a scientific research paradigm for the subsequent development of the community study on heat-sensitive moxibustion.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

Charcoal-processed traditional Chinese herbal medicine has various therapeutic effects， including astringing， hemostasis， anti-diarrhea， clearing heat， tonifying， and warming the interior. This paper summarizes the clinical application features， compatible experiences， dosages， and precautions for over 20 types of charcoal-processed herbal medicine in the treatment of gynecological bleeding disorders caused by dysfunctions such as dysfunctional uterine bleeding， endometriosis， uterine incision pseudocavity， and vaginal bleeding resulting from threatened miscarriage. The charcoal-processed herbal medicine include Huangqin （Scutellaria Baicalensis） Charcoal， Dahuang （Rheum Palmatum） Charcoal， Cebai （Platycladus Orientalis） Charcoal， Diyu （Sanguisorba Officinalis） Charcoal， Daji （Cirsium Setosum） Charcoal， Xiaoji （Cirsium Japonicum） Charcoal， Shengdi （Rehmannia Glutinosa） Charcoal， Aiye （Artemisia Argyi） Charcoal， Paojiang （Zingiber Officinale） Charcoal， Xuduan （Dipsacus Asper） Charcoal， Duzhong （Eucommia Ulmoides） Charcoal， Qiancao （Rubia Cordifolia） Charcoal， Puhuang （Typha Angustifolia） Charcoal， Shanzha （Crataegus Pinnatifida） Charcoal， Jingjie （Schizonepeta Tenuifolia） Charcoal， Xueyu （Carthamus Tinctorius） Charcoal， Zonglyu （Areca Catechu） Charcoal， Wumei （Prunus Mume） Charcoal， Shudahuang （Rheum Officinale） Charcoal， Lianfang （Nymphaea Alba） Charcoal， Mianmaguanzhong （Clematis Armandii） Charcoal， and Oujie （Nelumbo Nucifera） Charcoal.

Objective To reveal the scientific output and trends in pulmonary nodules/early-stage lung cancer prediction models. Methods Publications on predictive models of pulmonary nodules/early lung cancer between January 1, 2002 and June 3, 2023 were retrieved and extracted from CNKI, Wanfang, VIP and Web of Science database. CiteSpace 6.1.R3 and VOSviewer 1.6.18 were used to analyze the hotspots and theme trends. Results A marked increase in the number of publications related to pulmonary nodules/early-stage lung cancer prediction models was observed. A total of 12581 authors from 2711 institutions in 64 countries/regions published 2139 documents in 566 academic journals in English. A total of 282 articles from 1256 authors were published in 176 journals in Chinese. The Chinese and English journals which published the most pulmonary nodules/early-stage lung cancer prediction model-related papers were Journal of Clinical Radiology and Frontiers in Oncology, respectively. Chest was the most frequently cited journal. China and the United States were the leading countries in the field of pulmonary nodules/early-stage lung cancer prediction models. The institutions represented by Fudan University had significant academic influence in the field. Analysis of keywords revealed that multi-omics, nomogram, machine learning and artificial intelligence were the current focus of research. Conclusion Over the last two decades, research on risk-prediction models for pulmonary nodules/early-stage lung cancer has attracted increasing attention. Prognosis, machine learning, artificial intelligence, nomogram, and multi-omics technologies are both current hotspots and future trends in this field. In the future, in-depth explorations using different omics should increase the sensitivity and accuracy of pulmonary nodules/early-stage lung cancer prediction models. More high-quality future studies should be conducted to validate the efficacy and safety of pulmonary nodules/early-stage lung cancer prediction models further and reduce the global burden of lung cancer.

Objective To evaluate the reporting quality and influencing factors of patient-reported outcome (PRO) data in randomized controlled trials (RCTs) of lung cancer. Methods RCTs of lung cancer with PRO as either primary or secondary endpoints were searched from PubMed, EMbase, Medline, CNKI, Wanfang Data, and VIP databases between January 1, 2010 and April 20, 2024. Reporting quality of included RCTs were assessed based on the CONSORT-PRO extension. Descriptive statistics and bivariate regression analysis were used to describe the reporting quality and analyze the factors influencing the reporting quality. Results A total of 740 articles were retrieved. After screening, 53 eligible RCTs of lung cancer with 22 780 patients were included. The patients were mainly with non-small cell lung cancer (84.91%), with the median sample size of the included studies was 364.0 (160.5, 599.5) patients. The primary PRO tool used was the EORTC QLQ-C30 (60.38%). There were 52 (98.11%) studies whose PRO measured the domain of "symptom management of cough, dyspnea, fatigue, pain, etc.", and 45 (84.91%) studies measured "health-related quality of life". Multicenter studies accounted for 84.91%, and randomized non-blind trials accounted for 62.26%. PRO was used as the primary endpoint in 33.96% of the studies and as secondary endpoints in 66.04%. The reliability and validity of the PRO tools were explicitly mentioned in 11.32% and 7.55% of the studies, respectively. The average completeness of reporting according to the CONSORT-PRO guidelines was 60.00%, ranging from 25.00% to 93.00%. The main factors affecting the completeness of CONSORT-PRO reporting included sample size and publication year. For every increment in sample size, the completeness of reporting increased by 27.5% (SE=0.00, t=2.040, P=0.046). Additionally, studies published after 2018 had a 67.2% higher completeness of reporting compared to those published in or before 2018 (SE=17.8, t=–3.273, P=0.006). Conclusion The study reveals that the overall reporting quality of PRO in lung cancer RCTs is poor. Particularly, the reporting of PRO measures reliability and validity, PRO assumptions, applicability, and handling of missing data need further improvement. Future research should emphasize comprehensive adherence to the CONSORT-PRO guidelines.

Objective:To investigate the risk factors associated with post-prematurity respiratory disease (PPRD) in very preterm infants.Methods:A prospective cohort study was conducted, enrolling 369 very preterm infants who were admitted to the neonatal intensive care unit of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, within one week of birth from January 2019 to June 2023. Data on maternal and infant clinical characteristics, neonatal morbidities, and treatments during hospitalization were collected. The very preterm infants were divided into 2 groups based on whether they developed PPRD. Continuous variables were compared using Mann-Whitney U test, while categorical variables were compared using χ2 tests or continuity correction χ2 test. Multivariate Logistic regression analysis was used to identify the independent risk factors for PPRD in very preterm infants. Results:Among the 369 very preterm infants, 217 cases(58.8%) were male, with a gestational age of 30 (28, 31) weeks at birth and a birth weight of 1 320 (1 085, 1 590) g. Of these, 116 cases (31.4%) developed PPRD, while 253 cases (68.6%) did not. The very preterm infants in the PPRD group had a lower gestational age and lower birth weight (both, P<0.001). The PPRD group also had a higher proportion of males, lower Apgar scores at the 1 th minute after birth and the 5 th minutes after birth, a higher rate of born via cesarean delivery, and a higher incidence of bronchopulmonary dysplasia, more pulmonary surfactant treatment, longer durations of mechanical ventilation, longer total oxygen therapy, and lower Z-score for weight at discharge (all P<0.05). Multivariate Logistic regression analysis showed that gestational age ( OR=0.85, 95% CI 0.73-0.99, P=0.037), born via cesarean delivery ( OR=2.23, 95% CI 1.21-4.10, P=0.010), a duration of mechanical ventilation ≥7 days ( OR=2.51, 95% CI 1.43-4.39, P=0.001), and a Z-score for weight at discharge ( OR=0.82, 95% CI 0.67-0.99, P=0.040) were all independent risk factors for PPRD in very preterm infants. Conclusion:Very preterm infants with a small gestational age, born via cesarean section, mechanical ventilation ≥7 days, and a low Z-score for weight at discharge should be closely monitored for PPRD, and provided with standardized respiratory management after discharge.

Isosteviol is a tetracyclic diterpenoid compound obtained by hydrolysis of natural stevia glycoside under acidic conditions. It has many pharmacological activities, such as anti-tumor, hypoglycemic, anti-inflammatory and antibacterial. Due to its low water solubility, low activity and low bioavailability, isosteviol has poor performance. In order to overcome these shortcomings, scholars have obtained a large number of isosteviol derivatives with novel structures and excellent activity. In this paper, we review the recent progress in the research on the structure modification, biological activity, structure-activity relationship and microbial transformation of isosteviol, in order to provide a reference for the development of new drugs of isosteviol and its derivatives.

ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine （TCM）/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed， Embase， Web of Science， CNKI， Wanfang Data， and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1， 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ） and Reporting Items for Practice Guidelines in Healthcare （RIGHT）. ResultsA total of nine guidelines/consensuses were included after literature screening， with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows： scope and purpose （47.1%）， stakeholder involvement （41.0%）， rigor of development （21.6%）， clarity of presentation （40.2%）， applicability （19.0%）， and editorial independence （19.6%）. The recommendation level of the articles was B level （recommended after revision） for four articles and C level （not recommended） for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”， while other areas needed to be improved. Currently， there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness， scientific rigor， and transparency of these guidelines/consensuses.