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.

ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

AIM:To investigate the protective effects of Dendrobium officinale polysaccharide(DOP)on high glucose-induced apoptosis in retinal capillary pericytes and its potential mechanism involving mitochondrial function.METHODS:Retinal capillary pericytes were allocated into five groups: normal control(NC), high glucose(HG), and three DOP treatment groups(low, DOP-L; medium, DOP-M; high, DOP-H). Pericyte ultrastructure was analyzed using transmission electron microscopy(TEM). Apoptotic rate was quantified via Annexin V-FITC staining. Mitochondrial transmembrane potential was assessed using the JC-1 probe. Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were employed to measure expression levels of cytochrome C(Cyt C), B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), Caspase-9, and Caspase-3, respectively.RESULTS:Compared to the NC group, pericytes exposed to HG exhibited significant mitochondrial damage, elevated apoptotic rate, increased mRNA and protein expression of Cyt C, Bax, Caspase-9, and Caspase-3(all P<0.01), alongside a marked reduction in mitochondrial transmembrane potential and expression of Bcl-2 mRNA and protein(all P<0.01). In contrast, DOP treatment groups(DOP-M,DOP-H)dose-dependently ameliorated mitochondrial damage, reduced apoptotic rate, downregulated Cyt C, Bax, Caspase-9, and Caspase-3 expression, enhanced mitochondrial transmembrane potential, and upregulated Bcl-2 expression relative to the HG group(all P<0.05).CONCLUSION:DOP attenuates high glucose-induced apoptosis and mitochondrial injury in retinal capillary pericytes. The underlying mechanism may involve the restoration of mitochondrial transmembrane potential.

Background As one of the key populations in the prevention and treatment of iodine deficiency disorders, it is important to continuously monitor the iodine nutritional level of school-age children. The current reference interval for thyroid volume in China is based on age only, without taking into account differences in individual developmental levels, and the distribution of thyroid volume may vary regionally due to economic, demographic, and environmental factors. The current reference cut-off points for thyroid volume proposed by the World Health Organization are not based on the Chinese population. Objective To understand the iodine nutritional status and distribution of thyroid volume (Tvol) among children aged 8-10 years in Huangpu District, Shanghai, China, to identify impact factors of Tvol, and to propose a reference range upper limit for local thyroid health surveillance, so as to provide a basis for goiter control and prevention. Methods Six hundred children aged 8-10 years in Huangpu District were recruited in 2017, 2020, and 2023, and body height, weight, thyroid volume, urinary iodine, and iodine content of household edible salt were determined. A multilevel model was constructed using population density and area as regional variables, and age, body surface area (BSA), and body mass index (BMI) as potential impact factors for at the individual level, to assess their effects on thyroid volume. Quantile regression of thyroid volume was performed, and the 98th percentile (P₉₈) of thyroid volume was predicted based on age and BSA. Results The iodized salt coverage in the households of surveyed children in 2017, 2020, and 2023 was 72.0%, 57.0%, and 48.0%, respectively, and the iodized salt coverage decreased by year (χ²=24.31, P<0.001). The urinary iodine level of children in 2017 was higher than that in 2020 and 2023 (χ²=18.77, P<0.001). The Tvol medians of children in 2017, 2020, and 2023 were 2.29, 2.49, and 2.97 mL, respectively, and the Tvol increased by year (χ²=60.04, P<0.001). The proportion of goiter was higher in children in 2023 than in 2017 and 2020 (χ²=6.57, P<0.05). Sex differences were not statistically significant for urinary iodine levels, thyroid volume, and goiter. The median Tvol was 2.26, 2.58, and 2.76 mL in children of 8, 9, and 10 years old respectively, and the Tvol increased with age (χ²=49.02, P <0.001). Tvol was positively correlated with age, BSA, and BMI with correlation coefficients of 0.2846, 0.3723, and 0.2950, respectively. The final quantile regression model showed that the strongest effect of BSA was associated with the 98th percentile of Tvol. Multilevel models considering population density or area as regional variables failed to achieve convergence. Conclusion To establish the upper limit of the reference interval for thyroid volume of healthy children in Huangpu District, the effects of age and BSA should be considered at the individual level, and the upper limit of the normal interval for goiter screening is suggested to be the 98th percentile value of BSA at the same age. In addition, the adaptability of population density and regional area as indicators of regional aggregation of thyroid volume distribution still needs to be further explored.

Background The adverse effects of long working hours, shift rotation, and job stress on the physical and mental health of occupational populations require urgent attention. Objective To investigate and compare the positive rates of WMSDs between different industries, analyze the exposure status of long working hours, shift rotation, and job stress among key occupational groups, and evaluate the impacts of these factors on WMSDs in the manufacturing and service industries. Methods The study subjects were derived from key occupational populations in Yunnan Province, recruited by the Chinese National Occupational Health Literacy Monitoring Survey in 2022. A cross-sectional design was used for this survey. The key occupational populations were recruited from the secondary industry (manufacturing industry, metal mining and beneficiation industry, and non-metal mining and beneficiation industry) by stratified random sampling and from the tertiary industry (medical and healthcare industry, education industry, environmental sanitation industry, transportation industry, and express/takeaway delivery industry) by proportional probability sampling, and 12014 front-line workers were finally included as survey participants. General information, work-related factors (shift rotation, weekly working hours, job stress, etc.) and WMSDs assessment results were obtained through a web-based self-reported questionnaire, and the associations of long working hours, shift rotation, and job stress with WMSDs were analyzed using χ² test and logistic regression. Results The average positive rate of WMSDs among the key occupational groups in Yunnan Province was 77.2%. The positive rate of WMSDs in the secondary industry group was 69.4%, while it was 81.6% in the tertiary industry group, with a statistically significant difference (P<0.001). Among the eight surveyed sectors, the education sector had the highest positive rate of WMSDs (94.2%). The single-site WMSDs mainly involved the neck, shoulders, and low back. In the secondary industry, WMSDs was reported in 1−2 body parts, while in the tertiary industry, WMSDs was mainly reported in multiple (≥5) body parts. Long working hours (OR: 1.119, 1.165, 1.163, respectively), shift rotation (OR: 1.094, 1.199, 1.230, respectively), and job stress (OR: 1.795, 1.854, 2.006, respectively) were risk factors for WMSDs in the neck, shoulder, or low back, and all three were also risk factors for multi-site WMSDs. Moreover, as the number of involved body parts increased, the effects of long working hours and job stress became more pronounced. For 1-2, 3-4, and 5 or more body parts compared to no pain reported, their OR values were 0.971 (95%CI: 0.871, 1.082), 1.133 (95%CI: 1.004, 1.279), and 1.285 (95%CI: 1.155, 1.429) for long working hours, respectively, and the OR values were 1.009 (95%CI: 0.878, 1.160), 1.360 (95%CI: 1.174, 1.575), and 2.797 (95%CI: 2.471, 3.166) for job stress, respectively. Conclusion The positive rate of WMSDs is higher in the tertiary industry than that in the secondary industry among the key occupational groups in Yunnan Province. Long working hours, rotating shift work, and job stress could significantly increase the risk of WMSDs.

OBJECTIVE To investigate the effects and mechanism of total alkaloids of Corydalis Rhizoma （TAC） on the regulation of cuproptosis in rats with diabetic cardiomyopathy （DCM） based on silence information regulator 1（Sirt1）/tumor protein 53（P53）signaling pathway. METHODS DCM rat model was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. Thirty-two model rats were randomly divided into model group， TAC low-dose， medium-dose and high-dose groups （7， 10.5， 14 mg/kg）， with 8 rats in each group. An additional 8 rats were assigned to normal control group. Related drugs or normal saline were administered intragastrically in each group， once a day， for 4 weeks. After the last medication， the fasting blood glucose （FBG） levels of the rats were measured. The levels of myocardial creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in serum and myocardial tissue of rats were all detected. The pathological morphology， fibrosis degree， and Cu2+ deposition of myocardial tissue in rats were observed. The levels of Cu2+ and glutathione （GSH） in myocardial tissue， the expressions of Sirt1/P53 signaling pathway-related proteins [Sirt1， P53， solute carrier family 7 membrane 11 （SLC7A11）]， and iron-sulfur cluster-related proteins [ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， aconitase 2 （ACO2）， NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）， dihydrolipoamide acetyltransferase （DLAT）， dihydrolipoamide succinyltransferase （DLST）]， and heat shock protein 70 （HSP70） were all determined. RESULTS Compared with normal control group， the model group exhibited significantly elevated levels of FBG， CK， CK-MB and LDH in both serum and myocardial tissue， as well as increased 2+ levels of Cu in myocardial tissue and the expression of P53 and HSP70 proteins （P＜0.05）； the level of GSH and the expression levels of Sirt1， SLC7A11， FDX1， LIAS， ACO2， NDUFS8， DLAT， and DLST proteins in myocardial tissue were all significantly decreased （P＜0.05）； the myocardial tissue exhibited severe pathological damage， with numerous inflammatory cell infiltrations and significant fibrosis， as well as increased deposition of Cu2+. Compared with model group， most of the above quantitative indicators in rats were significantly reversed in TAC groups （P＜0.05）； the pathological damage to the myocardial tissue was alleviated， with reduced fibrosis and Cu2+ deposition. CONCLUSIONS TAC can ameliorate DCM in rats， and its mechanism of action may be related to activating the activity of the Sirt1/P53 signaling pathway， promoting the chelation of GSH with Cu2+， and inhibiting cuproptosis of cardiomyocyte.

ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum （PRP） on lung tissue， gut microbiota， and short-chain fatty acid （SCFA） metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group， model group， positive control group （Xiaoqinglong granules， 6.5 g·kg^-1）， and high-dose and low-dose PRP decoction groups （3.0， 1.5 g·kg^-1）， with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin （OVA） sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid （BALF） were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E （IgE）， interferon-γ （IFN-γ）， interleukin-4 （IL-4）， and BALF levels of interleukin-6 （IL-6） and interleukin-8 （IL-8） were quantified by enzyme-linked immunosorbent assay （ELISA）. Lung histopathology was assessed using hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） was employed to detect mucin 5AC （MUC5AC） and aquaporin 5 （AQP5） protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis， and fecal SCFA levels were measured by gas chromatography-mass spectrometry （GC-MS）. ResultsCompared with the normal group， the model group exhibited significantly increased airway resistance value （RI） （P<0.05）， elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF （P<0.05）， increased serum IgE and IL-4 levels （P<0.05）， with reduced IFN-γ levels （P<0.05）. It also showed thickened bronchial walls， widened alveolar septa， narrowed lumens， and mucus plugs in lung tissue， upregulated MUC5AC protein expression and downregulated AQP5 protein expression （P<0.05）， decreased relative abundance of beneficial gut microbiota （Firmicutes， Clostridia， Clostridiales， Lactobacillaceae， and Lactobacillus）， and increased abundance of harmful microbiota （Bacteroidetes， Bacteroidia， Bacteroidales， Muribaculaceae， and Muribaculum）. In addition， the model group presented reduced fecal SCFA levels （acetate， propionate， and butyrate） （P<0.05）. After the intervention of PRP decoction， compared to the model group， all drug administration groups showed decreased RI （P<0.05）， increased phenol red excretion， declined eosinophil and neutrophil counts and IL-6， IL-8， IgE， and IL-4 levels （P<0.05）， and improved IFN-γ levels （P<0.05） and lung pathology improved. The MUC5AC protein expression decreased （P<0.05）， and the AQP5 protein expression increased （P<0.05）. The disorder of gut microbiota was improved， and the diversity of gut microbiota was restored， with a significantly increased relative abundance ratio of beneficial microbiota （P<0.05） and a significantly reduced relative abundance ratio of harmful microbiota （P<0.05）. The SCFA levels （acetate， propionate， and butyrate） increased （P<0.05）. The efficacy indicators of serum inflammatory factors （IgE， IL-4， and IFN-γ）， phlegm-resolving effect， airway resistance， total pathological score， and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis， promoting beneficial gut microbiota， enhancing SCFA production， restoring the balance of gut microbiota， and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.

ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum （PRP） on lung tissue， gut microbiota， and short-chain fatty acid （SCFA） metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group， model group， positive control group （Xiaoqinglong granules， 6.5 g·kg^-1）， and high-dose and low-dose PRP decoction groups （3.0， 1.5 g·kg^-1）， with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin （OVA） sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid （BALF） were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E （IgE）， interferon-γ （IFN-γ）， interleukin-4 （IL-4）， and BALF levels of interleukin-6 （IL-6） and interleukin-8 （IL-8） were quantified by enzyme-linked immunosorbent assay （ELISA）. Lung histopathology was assessed using hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） was employed to detect mucin 5AC （MUC5AC） and aquaporin 5 （AQP5） protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis， and fecal SCFA levels were measured by gas chromatography-mass spectrometry （GC-MS）. ResultsCompared with the normal group， the model group exhibited significantly increased airway resistance value （RI） （P<0.05）， elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF （P<0.05）， increased serum IgE and IL-4 levels （P<0.05）， with reduced IFN-γ levels （P<0.05）. It also showed thickened bronchial walls， widened alveolar septa， narrowed lumens， and mucus plugs in lung tissue， upregulated MUC5AC protein expression and downregulated AQP5 protein expression （P<0.05）， decreased relative abundance of beneficial gut microbiota （Firmicutes， Clostridia， Clostridiales， Lactobacillaceae， and Lactobacillus）， and increased abundance of harmful microbiota （Bacteroidetes， Bacteroidia， Bacteroidales， Muribaculaceae， and Muribaculum）. In addition， the model group presented reduced fecal SCFA levels （acetate， propionate， and butyrate） （P<0.05）. After the intervention of PRP decoction， compared to the model group， all drug administration groups showed decreased RI （P<0.05）， increased phenol red excretion， declined eosinophil and neutrophil counts and IL-6， IL-8， IgE， and IL-4 levels （P<0.05）， and improved IFN-γ levels （P<0.05） and lung pathology improved. The MUC5AC protein expression decreased （P<0.05）， and the AQP5 protein expression increased （P<0.05）. The disorder of gut microbiota was improved， and the diversity of gut microbiota was restored， with a significantly increased relative abundance ratio of beneficial microbiota （P<0.05） and a significantly reduced relative abundance ratio of harmful microbiota （P<0.05）. The SCFA levels （acetate， propionate， and butyrate） increased （P<0.05）. The efficacy indicators of serum inflammatory factors （IgE， IL-4， and IFN-γ）， phlegm-resolving effect， airway resistance， total pathological score， and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis， promoting beneficial gut microbiota， enhancing SCFA production， restoring the balance of gut microbiota， and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.

The rapid rise and fast development of artificial intelligence (AI) has brought unprecedented opportunities and challenges to all sectors, including disease prevention control. Malaria is one of the world’s most devastating infectious diseases. This article summarizes the advances in the research and application of AI-empowered malaria control programmes, analyzes key challenges during the implementation of malaria control programmes, and proposes future development directions and research proprieties, so as to provide insights into facilitating the translation of AI-driven strategies in global infectious disease control efforts.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.