Objective: To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment. Methods: From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated. Results: The average outdoor temperature during on site measurement was 4.00(0.20，7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05). Conclusions There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

ObjectiveIn traditional Chinese medicine (TCM), the foundational doctrine that the eyes reflect the essence of the internal viscera establishes ocular observation as a cornerstone of diagnostic practice. Specifically, the morphological characteristics and coloration variations of the scleral microvasculature serve as critical clinical indicators for assessing the dynamic balance of Qi and Blood, as well as the pathological status of internal organs. Historically, however, TCM eye diagnosis has relied predominantly on the subjective clinical experience and visual acuity of individual practitioners, leading to inherent challenges in standardization and reproducibility. While automated computer-aided diagnostic systems offer a promising solution, existing vessel segmentation algorithms encounter significant domain-specific bottlenecks when applied to scleral imagery. These challenges primarily stem from the highly reflective and moist nature of the ocular surface, which generates severe reflective interference. Furthermore, the inherent low contrast of fine capillary networks against complex background textures, compounded by non-uniform illumination, frequently results in high false-positive rates, misdetections, and severe vessel fragmentation. To address these critical limitations and advance the objective quantification of TCM diagnostics, this paper proposes a novel, highly robust sclera vessel segmentation framework that innovatively integrates Frangi-Sato dual-filter adaptive enhancement with pixel-level reflection detection. MethodsThe proposed methodology systematically addresses the segmentation pipeline through three synergistic stages. First, to overcome the structural limitations of single-filter approaches, a multi-scale weighted fusion strategy is meticulously designed to harness the complementary extraction capabilities of both Frangi and Sato filters. This adaptive enhancement optimally balances the preservation of main vessel trunk continuity with the heightened sensitivity required for delineating delicate, low-contrast peripheral capillaries. Second, to tackle the persistent issue of reflective highlights, a sophisticated multi-feature synergistic reflection detection module is introduced. By jointly analyzing local information entropy, gradient field variations, and intensity statistical distributions, this module achieves precise, pixel-level identification and elimination of reflective artifacts without compromising the underlying vascular structures. Finally, a dual-level adaptive thresholding strategy, featuring an innovative “core protection” mechanism, is implemented. This critical step effectively suppresses complex background noise while rigorously preserving the structural and topological integrity of the intricate vessel network, preventing the structural breaks often seen in conventional binarization methods. ResultsThe efficacy of the proposed framework was rigorously evaluated using both self-constructed clinical datasets specifically acquired for TCM research and standardized public datasets. Extensive experimental results demonstrate that the proposed method consistently outperforms state-of-the-art traditional approaches and contemporary deep learning models. Specifically, the proposed method achieves a Dice similarity coefficient of approximately 0.71 on the private clinical dataset, and secures the best performance across the majority of quantitative metrics on both datasets. Notably, the framework exhibits exceptional robustness and generalization capabilities in highly challenging scenarios characterized by intense reflective interference, low signal-to-noise ratios, and cross-domain image variations. ConclusionThis study successfully realizes the high-integrity, automated segmentation of scleral vessel networks under complex clinical imaging conditions. By overcoming the fundamental algorithmic challenges of reflection interference and micro-vessel loss, the proposed methodology provides potential support for the digitization, objective standardization, and intelligent advancement of modern TCM eye diagnosis systems.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.