Osteoarthritis （OA） and stroke are common clinical diseases that reduce patients' quality of life and place a burden on families and society. Ruyi Zhenbaowan， a classic prescription in Tibetan medicine， have the functions of clearing heat， awakening the brain and opening orifices， relaxing tendons and promoting meridian circulation， and eliminating yellow water. Clinically， they are used to treat osteoarthritis， post-stroke sequelae， neuropathic pain， and other related conditions. Modern pharmacological studies have demonstrated their anti-inflammatory， analgesic， and nerve-repairing effects. However， current research remains insufficient regarding the appropriate indications， timing， and efficacy of this medicine in treating relevant diseases. To enhance clinicians' understanding of this medicine and promote its standardized and rational clinical use， a panel of national experts， including clinical specialists， Tibetan medicine practitioners， pharmacologists， and methodologists， formulated this consensus based on clinical experience and evidence-based practice. The Cochrane systematic review framework， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system， and the nominal group method were employed to generate seven graded recommendations and 19 consensus-based suggestions. These recommendations clearly define the key points in the clinical application of Ruyi Zhenbaowan， including therapeutic indications， dosage and administration， treatment duration， and medication safety. The consensus specifically addresses the clinical efficacy， appropriate timing of administration， dosage strategies， treatment cycles， and combination medication strategies for treating osteoarthritis and stroke and provides an overview of safety considerations. The aim is to provide standardized guidance for hospitals and healthcare institutions nationwide to ensure the rational application of Ruyi Zhenbaowan in the treatment of osteoarthritis and stroke， reduce medication-related risks， and further leverage its clinical advantages. This consensus has been approved and issued by the China Association of Chinese Medicine， with the standard number GS/CACM 369-2024.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

Objective To establish a novel clinical application process of the optical surface monitoring system(OSMS)guided volumetric modulated arc therapy(VMAT)for total body irradiation(TBI),and to assess the accuracy and effectiveness of OSMS in inter-fractional auxiliary positioning before radiotherapy and real-time monitoring of intra-fractional motion during radiotherapy.Methods A retrospective analysis was conducted on 15 leukemia patients who underwent OSMS-guided VMAT-TBI before hematopoietic stem cell transplantation.CT simulation positioning was performed,and the whole-body image data which were collected in head-first supine position(HFS)and feet-first supine position(FFS)were transmitted to the treatment planning system for image registration,multicenter VMAT planning and dose verification.The prescription dose was 800 cGy in 4 fractions twice daily.OSMS was used to assist positioning before delivery,and CBCT was used for position verification.During treatment,OSMS was used for monitoring.The intra-fractional error monitored by OSMS in real time was obtained by analyzing the offline log files.Results The mean dose and coverage of the target area in HFS plan were(905.4±19.0)cGy and 93.0%±2.8%.The mean doses to lung and kidney were(603.7±55.7)cGy and(600.4±49.6)cGy,respectively,and the maximum dose to the lens was(393.9±58.9)cGy.The mean dose and coverage of the target area in FFS plan were(888.5±58.9)cGy and 94.0%±3.2%;and the maximum dose at the junction was(1148.9±72.9)cGy.Fractional treatment delivery time was(75.1±15.1)min.OSMS-assisted positioning was carried out before delivery,and the total deviations of CBCT three-dimensional vector in translational and rotation directions were(2.71±1.96)mm and 0.91°±0.90°,respectively.The three-dimensional vector deviation of the intra-fractional motion amplitude in translational direction monitored by OSMS during the treatment was(1.95±1.88)mm,of which the deviation within 1 mm accounted for 57.5%,79.7%and 62.1%in longitudinal,lateral and vertical directions,respectively.The three-dimensional vector deviation in rotation direction was 0.76°±0.72°,of which the deviation within 1°accounted for 93.1%,85.7%and 94.3%in rotation,pitch and roll directions,respectively.Conclusion VMAT simplifies TBI process,while improving target coverage and organs-at-risk sparing.The use of OSMS can reduce positioning errors,especially rotation errors.In order to ensure the accurate implementation of TBI and the safety of patients,it is necessary to use OSMS for auxiliary positioning and intra-fractional position monitoring.

Objective To investigate the fluctuations in the population density of Aedes albopictus and changes in the population density of Ae. albopictus in different geographical areas and different breeding habitats in Guangdong Province from 2018 to 2023, so as to provide insights into prevention and control of mosquito-borne infectious diseases in the province. Methods Ae. albopictus surveillance sites were assigned in 1 609 townships (streets) from 121 districts (counties) of 21 cities in Guangdong Province during the period between March and November from 2018 to 2023. The surveillance of the population density of Ae. albopictus was performed once a month in each surveillance site, and once a month in specific settings in cities where dengue were highly prevalent in Guangdong Province from December to February of the next year during the period from 2018 through 2023. Four streets (villages) were selected in each surveillance site according to the geographic orientation, and mosquito ovitraps were assigned in gardens, rooftops or public green belts at residential areas, parks, hospitals and construction sites. All mosquito ovitraps were collected, and the mosquito ovitrap index (MOI) was calculated. The population density of Ae. albopictus was classified into four grades in each surveillance site according to MOI, including no risk, low risk, medium risk and high risk. The risk classification of the Ae. albopictus density was analyzed in each surveillance site each year from 2018 to 2023, and the population density of Ae. albopictus was analyzed at different months and in different geographical areas and breeding habitats. Results A total of 118 241 Ae. albopictus surveillance sites were assigned in 21 cities of Guangdong Province from 2018 to 2023, and there were 68.26% of the surveillance sites with the population density of Ae. albopictus that met the requirements for dengue prevention and control, among which low, medium and high risk surveillance sites accounted for 23.61%, 6.67% and 1.47%. The risk classification of the Ae. albopictus density increased rapidly in Guangdong Province since April to May each year from 2018 to 2023, and then gradually reduced since September to October, with the peak during the period between May and July. The mean MOI was 4.21 at each surveillance site in Guangdong Province during the period from 2018 to 2023, with 4.69, 4.80, 4.38, 3.82, 3.38, and 4.33 from 2018 to 2023, respectively. The MOI was 4.35, 4.43, 3.53 and 3.58 in the Pearl River Delta region, and eastern, western, and northern Guangdong Province, respectively, and was 4.18, 5.44, 4.75, 3.24, 4.27 and 3.70 in residential areas, parks, construction sites, hospitals, waste collection stations, and other breeding habitats, respectively. Conclusions The population density of adult Ae. albopictus peaked in Guangdong Province during the period between May and July from 2018 to 2023, with a high density of Ae. albopictus in the Pearl River Delta region and eastern Guangdong Province. Targeted Ae. albopictus control measures are recommended to be implemented prior to the peak of the Ae. albopictus population density to reduce the development of mosquito-borne infectious diseases.

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.