As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective To evaluate the efficacy and safety of intraoperative pleural irrigation with Nocardia rubra cell-wall skeleton (N-CWS) for reducing pleural effusion drainage after radical surgery for lung cancer. Methods A retrospective analysis was conducted on the clinical data of lung cancer patients who underwent lobectomy and mediastinal lymph node dissection at the First Affiliated Hospital of Xiamen University between December 2024 and May 2025. Patients were divided into a control group and an irrigation group based on the intraoperative use of N-CWS. Patients in the irrigation group received pleural irrigation with 800 μg of N-CWS diluted in 10 mL of normal saline. The following outcomes were compared between the two groups: pleural effusion drainage volume at 0-24 h, 24-48 h, and 48-72 h postoperatively, degree of air leak, chest tube duration, postoperative length of stay, and the incidence of adverse events (fever, chest pain, and nausea and vomiting). Results A total of 245 patients were included (97 males, 148 females) with a mean age of (61.28±6.26) years, with 205 in the control group and 40 in the irrigation group. Compared to the control group, the irrigation group showed significantly lower pleural effusion drainage volumes at 0-24 h, 24-48 h, and 48-72 h, as well as shorter chest tube duration and postoperative length of stay (all P<0.05). There was no statistical difference in the degree of postoperative air leak (P=0.661). No significant differences were observed between the two groups regarding the highest body temperature within 72 h post-surgery (P=0.130), fever grade (P=0.196), severity of chest pain (P=0.105), or the incidence of nausea and vomiting (P=0.376). Conclusion Intraoperative pleural irrigation with N-CWS in patients undergoing lobectomy and mediastinal lymph node dissection for lung cancer can significantly reduce postoperative pleural effusion drainage volume, shorten chest tube duration and length of hospital stay. The procedure is safe and feasible.

Colorectal cancer is a malignant tumor that originates from the epithelial cells of the colon and rectum. It has the third highest incidence and the second highest mortality rate among malignant tumors worldwide. With the rapid development of the economy and the increasing Westernization of dietary habits in China， its incidence in China has been rising year by year. Over the past decade， despite the introduction of numerous treatment methods for colorectal cancer， the efficacy of existing therapies remains unsatisfactory. In recent years， traditional Chinese medicine （TCM） has become a major focus in the treatment of colorectal cancer due to its advantages of multi-target， multi-pathway mechanisms and low toxicity and side effects. Vascular endothelial growth factor （VEGF） is an important angiogenic factor that promotes blood vessel formation， providing nutrients and oxygen for tumor growth. It also increases vascular permeability， allowing tumor cells to easily pass through the blood vessel wall into other tissues， thereby facilitating metastasis. Several studies have shown that TCM can inhibit tumor angiogenesis and lymphangiogenesis， promote tumor cell apoptosis， and inhibit the proliferation of colorectal cancer cells by acting on the VEGF signaling pathway， thereby delaying tumor growth. In recent years， research in this field has been rapidly updated， but there is a lack of relevant summaries， making subsequent literature searches inconvenient. Therefore， this article focuses on the physiological functions of the VEGF signaling pathway， its role in the occurrence of colorectal cancer， and the intervention of TCM on VEGF， providing a supplement and summary of relevant information to offer a reference for future research in this area.

ObjectiveTo investigate the effects of Xijiao Dihuangtang （XJDHT） on mice with sepsis and cellular models of sepsis and explore its molecular mechanism in alleviating sepsis-induced inflammatory responses via regulating pyruvate kinase M2 （PKM2）-mediated one-carbon metabolism pathway. MethodsForty C57BL/6N mice were randomly divided into four groups： normal group， model group， low-dose XJDHT group （7.7 g·kg^-1）， and high-dose XJDHT group （15.4 g·kg^-1）. After one week of continuous gavage， sepsis was induced using cecal ligation and puncture （CLP） in groups except the normal group. 24 h after the surgery， mortality rates in all groups were recorded， and serum cytokines were measured by enzyme linked immunosorbent assay （ELISA）. Lung histopathology was examined by hematoxylin-eosin （HE） staining. During the in vitro experiment， the human monocytic leukemia cell line （THP-1） was exposed to various concentrations of XJDHT and treated with lipopolysaccharide （LPS） at a final concentration of 2 mg·L^-1 for 24 h. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay. Protein levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） were measured by Western blot. Transcriptome sequencing was performed to analyze differentially expressed genes in all groups and conduct gene ontology （GO） enrichment. Key genes in the one-carbon metabolism pathway， including pyruvate kinase M2 （PKM2）， 5-methyltetrahydrofolate-homocysteine methyltransferase （MTR）， and phosphoglycerate dehydrogenase （PHGDH）， were verified by Western blot. A PKM2 inhibition model was established using shikonin for further protein expression analysis. ResultsAnimal experiments showed that compared with the normal group， the model group exhibited significantly elevated body temperature and lung pathology （P<0.01） and increased serum TNF-α and IL-1β levels （P<0.01）. High-dose XJDHT reduced body temperature and lung tissue damage （P<0.01） and significantly decreased serum TNF-α and IL-1β levels （P<0.01）. Low-dose XJDHT treatment showed no significant temperature change （P<0.01） but reduced serum TNF-α and IL-1β levels （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Cell experiments demonstrated that compared to the normal group， the model group showed elevated protein expressions of TNF-α and IL-1β in THP-1 cells （P<0.01）， decreased Bcl-2/Bax ratio， and increased apoptosis （P<0.01）. Transcriptome sequencing and Western blot revealed significant differences in the expression of TNF-α， IL-1β， and one-carbon metabolism genes （PKM2， MTR， and PHGDH） （P<0.01）. Compared to the model group， high-dose XJDHT significantly increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.01） and effectively reduced cell apoptosis （P<0.01） while down-regulating protein expressions of TNF-α， IL-1β， PKM2， and MTR （P<0.01）. Low-dose XJDHT moderately increased Bax/Bcl-2 ratio and PHGDH protein expression （P<0.05）， reduced apoptosis （P<0.05）， and decreased IL-1β and MTR protein levels （P<0.05， P<0.01）， but there were no significant changes in TNF-α and PKM2 expression. After PKM2 inhibition by shikonin in THP-1 cells， the expression of protein related to one-carbon metabolism was detected. Compared with the blank group， the LPS-induced model group showed significantly upregulated PKM2 and MTR protein expression （P<0.01） and downregulated PHGDH expression （P<0.01）. Compared with the model group， shikonin treatment significantly reduced PKM2 expression （P<0.05）， increased PHGDH expression （P<0.01）， and decreased MTR expression （P<0.05）. ConclusionXJDHT can inhibit the release of inflammatory factors in sepsis， and its mechanism is related to the intervention of the PKM2-regulated one-carbon metabolism pathway in macrophages.

ObjectiveTo investigate the differences in efficacy and endogenous metabolic mechanisms of Anmeidan with combined use of raw and fried Ziziphi Spinosae Semen and its disassembled prescriptions in treating anxiety and cognitive impairment in insomnia rats. MethodsSixty rats were randomly divided into six groups （n=10 per group）： blank group， model group， suvorexant group （30 mg·kg^-1）， Anmeidan group （9.09 g·kg^-1）， Anmeidan with absence of raw Ziziphi Spinosae Semen group （7.38 g·kg^-1）， and Anmeidan with absence of fried Ziziphi Spinosae Semen group （7.38 g·kg^-1）. An insomnia model was constructed by intraperitoneal injection of para-chlorophenylalanine （PCPA）， followed by gavage administration of Anmeidan or its disassembled prescriptions. Anxiety levels were assessed using the open field test， while cognitive ability was evaluated via the novel object recognition test. The pathological morphology of hippocampal neurons was examined using electron microscopy. Serum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） for principal component analysis， metabolic profiling， identification of differential metabolites， and metabolic pathway analysis. ResultsCompared with the blank group， the model group exhibited significantly increased exercise mileage， exercise time， and the ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones exhibited a marked increase （P<0.05， P<0.01）， while the novel object recognition index significantly decreased （P<0.05）. Compared with the model group， the Anmeidan and suvorexant groups showed significantly reduced exercise mileage and exercise time （P<0.01）. The ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones decreased （P<0.05）， and a significant increase in the novel object recognition index （P<0.01）. However， the disassembled prescription groups showed no significant improvement in open field test and novel object recognition test indices. Electron microscopy revealed that the Anmeidan group improved the pathological morphology of hippocampal neurons in insomnia rats. Metabolomics analysis identified 10 potential differential metabolites associated with Anmeidan's therapeutic effects， involving metabolic pathways related to phenylalanine and tryptophan biosynthesis and metabolism， as well as the serotonergic pathway. ConclusionThe combined use of raw and fried Ziziphi Spinosae Semen in Anmeidan is more effective than its disassembled prescriptions in alleviating anxiety and cognitive impairment in PCPA-induced insomnia rats. The underlying mechanism may be associated with metabolic pathways related to phenylalanine， tryptophan， and serotonin.

ObjectiveTo investigate the level of hepatitis B surface antibody (anti-HBs) among preschool children (aged 3‒6 years) and primary and secondary school students in Tonglu County, Zhejiang Province, to evaluate the effectiveness of hepatitis B vaccination, and to provide a basis for hepatitis B prevention and control in the region. MethodsAs part of the 2023 Tonglu County Urban and Rural Residents Health Examination Program, blood samples were collected during health check-ups. Fingertip blood samples were obtained from preschool children, while venous blood samples were collected from primary and secondary school children. The anti-HBs levels in blood (positive + / negative -) were qualitatively tested using hepatitis B surface antibody test kits (latex method). The differences in anti-HBs positivity rates among different age groups were analyzed. ResultsBetween April 1, 2023 and June 30, 2023, a total of 52 919 individuals were surveyed, including 11 973 preschool children and 40 946 primary and secondary school students. The overall anti-HBs positivity rate was 39.74%, with the highest positivity rate observed among preschool children (60.20%). Age was negatively correlated with the anti-HBs positivity rate (P<0.001). No significant gender differences in anti-HBs positivity rates were observed. The anti-HBs positive rate in rural areas was higher than that in urban areas, with statistically significant differences across school grade groups (primary grades 1‒3, grades 4‒6, middle school, and high school) (P<0.001). ConclusionThe anti-HBs positivity rate among preschool and school-age children in Tonglu County decreases with age and remains relatively low. It is recommended to strengthen the monitoring of hepatitis B antibody levels and promote health education among preschool and school-age children. Children who have not completed the full hepatitis B vaccination should receive timely catch-up vaccination.

BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

Since its establishment in 2016, the National Rare Diseases Registry System of China (NRDRS) has accumulated valuable case data and bio-specimen for basic and clinical research on rare diseases in China. However, the emerging challenges in clinical diagnosis and treatment of rare diseases make it unable for data and resource platform to fully meet the diversified needs. Under this backdrop, we have developed a protocol to optimize and upgrade the system based on the core functions of the NRDRS platform. The goal is to leverage intelligent digital technologies to transform NRDRS into a new platform integrating multimodal data and auxiliary diagnostic and treatment functions. It is specified as the development and construction of "one platform and four intelligent tools." Currently, we have upgraded and developed NRDRS platform, intelligent tool for genotype-phenotype analysis of rare diseases, AI-assisted diagnostic tool for rare diseases, remote multidisciplinary diagnosis and teaching tool for rare diseases, drug screening and validation tool for rare diseases. The next step will focus on the promotion of the application of these tools in clinical settings in order to address the issue of severe imbalance in the allocation of resources for the diagnosis and treatment of rare diseases. This article provides an overview of the digital and intelligent upgrades of the NRDRS, the trials in applications in clinical settings, and direction in the future.

BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.