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 analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) among college students in Yangzhou from 2020 to 2024, so as to provide a scientific basis for developing prevention and control strategies. Methods: An epidemiological investigation was conducted among 162 college students with PTB, and 7 134 of their contacts were screened. Data were obtained from the tuberculosis information management system and on campus screening records. Using descriptive epidemiological methods, trends in incidence, seasonal distribution, and bacteriological characteristics were analyzed. Results: From 2020 to 2024, the annual average incidence of pulmonary tuberculosis among college students in Yangzhou was 29.42 per 100 000, showing an overall fluctuating downward trend ( χ 2=12.36, P <0.01). Cases were mainly concentrated in summer and autumn, with the highest proportion in autumn (41.36%, 67/162), followed by summer (23.46%, 38/162). The proportion of etiologically positive cases increased from 37.21% in 2020 to 71.43% in 2024; among positive cases, the proportion of latent tuberculosis infection (LTBI) decreased from 66.67% (10/15) to 26.67% (4/15). The etiological positive rate was higher in females than in males ( χ 2= 11.76 , P <0.01). Comparison of screening methods showed that among index cases, the LTBI detection rate of the recombinant Mycobacterium tuberculosis fusion protein skin test (C-TST) was higher than that of the tuberculin skin test (TST), but the difference was not statistically significant ( χ 2=0.65, P =0.42); among close contacts, the detection rate of TST was higher than that of C-TST (15.1%,10.1%; χ 2=5.23, P <0.05). Conclusion From 2020 to 2024, the annual average incidence of pulmonary tuberculosis among college students in Yangzhou showed an overall fluctuating downward trend, with differences in TB infection screening methods and gender.

Objective To discuss the main pathological types and imaging characteristics of pulmonary nodules that are highly suspected to be malignant in clinical practice but are pathologically confirmed to be benign. Methods A retrospective analysis was performed on the clinical data of patients with pulmonary nodules who were initially highly suspected of malignancy but were subsequently pathologically confirmed to be benign. These patients were treated at the First Affiliated Hospital of Xiamen University from December 2020 to April 2023. Based on the outcomes of preoperative discussions, the patients were categorized into a benign group and a suspicious malignancy group. The clinical data and imaging characteristics of both groups were compared. Results A total of 232 patients were included in the study, comprising 112 males and 120 females, with a mean age of (50.7±12.0) years. Among these, 127 patients were classified into the benign group, while 105 patients were categorized into the suspicious malignancy group. No statistically significant differences were observed between the two groups regarding age, gender, symptoms, smoking history, or tumor history (P>0.05). However, significant differences were noted in nodule density, CT values, margins, shapes, and malignant signs (P＜0.05). Further analysis revealed that in the suspicious malignancy group, solid nodules were predominantly characterized by collagen nodules and fibrous tissue hyperplasia (33.3%), followed by tuberculosis (20.4%) and fungal infections (18.5%). In contrast, non-solid nodules were primarily composed of collagen nodules and fibrous tissue hyperplasia (41.2%) and atypical adenomatous hyperplasia (17.7%). Conclusion Benign pulmonary nodules that are suspected to be malignant are pathologically characterized by the presence of collagen nodules, fibrous tissue hyperplasia, tuberculosis, atypical adenomatous hyperplasia, and fungal infections. Radiologically, these nodules typically present as non-solid lesions and may exhibit features suggestive of malignancy, including spiculation, lobulation, cavitation, and pleural retraction.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases， malignant tumors， central nervous system diseases， and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development， the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe， America， and China， the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects， including lack of relevant laws and regulations， a higher risk of radiopharmaceuticals， dilemmas in ethical review， and insufficient radiation protection. Response principles and measures were proposed from four aspects， including improving regulations and policies， enhancing radiological protection for all parties involved in the research， strengthening ethical review， and reinforcing the training of relevant personnel， to enhance the quality and level of clinical research on radiopharmaceuticals.

Depression is a psychiatric disorder whose main symptoms include low mood， loss of interest， anxiety， sleep disturbances， and changes in appetite. Orexin， a neuropeptide located in hypothalamic neurons， has a wide range of projections throughout the central nervous system and is involved in various behavioral modulations related to depression. This study systematically reviewed the effects of orexin and its receptor-related drugs on depression and found that orexin could exert complex regulatory effects on multiple brain regions by binding to related receptors， affecting emotions， sleep， anxiety， etc. The abnormal state of expression of plasma orexin in patients with depression was found. Exogenous orexin-A， selective orexin receptor 1 antagonists （SORA1s）， selective orexin receptor 2 antagonists （SORA2s）， and dual orexin receptor antagonists （DORAs） have demonstrated antidepressant-like effects in various animal models of depression. Among them， clinical trials involving exogenous orexin-A are relatively scarce. Drugs related to SORA1s and SORA2s， such as JNJ-61393215 and Setorexant， have made significant progress in the treatment of depression. DORAs， such as Suvorexant， Lemborexant， and Daridorexant， are primarily used to treat insomnia. Notably， Suvorexant has also shown potential in alleviating symptoms of anxiety and depression.

Nuclear factor-erythroid 2-related factor 2 （Nrf2）/glutathione peroxidase 4 （GPX4） signaling pathway plays a key role in the occurrence and development of tumors， and is involved in tumor cell proliferation， apoptosis， ferroptosis， invasion， migration， and drug resistance. Based on the Nrf2/GPX4 signaling pathway， this paper summarizes the research progress of the anti- tumor effects of traditional Chinese medicine. It is found that flavonoids （ginkgetin， luteolin， etc.）， terpenoids （atractylenolide， cucurbitacin B， etc.）， saponins （polyphyllin Ⅰ， polyphyllin Ⅶ）， ester （brusatol） and other effective components， and traditional Chinese medicine extracts （total coumarins in Pileostegia tomentella and total flavonoids of Pterocarya hupehensis Skan）， traditional Chinese medicine compounds （Fushao diqin fang， Xiaoai jiedu fang， etc.） can promote ferroptosis in tumor cells by inhibiting Nrf2/GPX4 signaling pathway and the expressions of its upstream and downstream factor proteins， as well as by increasing Fe2+ levels and lipid peroxidation， thereby exerting an antitumor effect.

Background Metals and metalloids in fine particulate matter (PM_2.5) may cause damage to the respiratory and circulatory systems of the human body, and long-term exposure is prone to causing chronic poisoning, cancer, and other adverse effects. Objective To assess the distribution characteristics of metals and metalloids in outdoor PM_2.5 in a southern city of China, conduct source apportionment, and evaluate the associated health risks, thereby providing theoretical support for further pollution control measures. Methods PM_2.5 samples were collected in districts A, B, and C of a southern China city, and the concentrations of 17 metals and metalloids were detected by inductively coupled plasma-mass spectrometry (ICP-MS). Pollution sources were assessed through enrichment factor and principal components analysis, and the main pollution sources were quantified using absolute principal component scores-multivariate linear regression (APCS-MLR). Health risks were evaluated based on the Technical guide for environmental health risk assessment of chemical exposure (WS/T777—2021). Results The ambient air PM_2.5 concentrations in the city were higher in winter and spring, and lower in summer and autumn. The annual average concentrations of ambient PM_2.5 in districts A, B, and C were 36.7, 31.9, and 24.4 μg·m⁻³, respectively. The ambient PM_2.5 levels in districts B and C were below the second-grade limit set by the Ambient air quality standards (GB 3095—2012). The enrichment factors of cadmium (Cd), aluminum (Al), and antimony (Sb) were greater than 10, those of copper (Cu), lead (Pb), arsenic (As), nickel (Ni), mercury (Hg), and molybdenum (Mo) fell between 1 and 10, and those of manganese (Mn), vanadium (V), chromium (Cr), cobalt (Co), barium (Ba), beryllium (Be), and uranium (U) were below or equal to 1. The comprehensive evaluation of source analysis showed that the main pollution sources in districts A and C and the whole city were coal-burning. In district B, the main pollution source was also coal combustion, followed by industrial process sources and dust sources. The carcinogenic risks of As and Cr were between 1×10⁻⁶ and 1×10⁻⁴. However, the hazard quotients for 15 metals and metalloids in terms of non-carcinogenic risk were below 1. Conclusion Cr and As in the atmospheric PM_2.5 of the city present a certain risk of cancer and should be paid attention to. In addition, preventive control measures should be taken against relevant pollution sources such as industrial emission, dust, and coal burning.

BACKGROUND:Scholars at home and abroad consider New Zealand rabbits to be an ideal model animal because of the similar anatomical morphology of the lumbar spine to that of the human lumbar spine.There is a lack of systematic comparison of different ways to establish rabbit intervertebral disc degeneration models under X-ray guidance. OBJECTIVE:To establish a rabbit model of lumbar disc degeneration using X-ray guided acupuncture,end-plate injection and combined method,and to compare the modeling effects of these three methods. METHODS:Eighteen 6-month-old New Zealand white rabbits were randomly selected and divided into four groups:acupuncture group,endplate injection group,combined group and blank control group.In the acupuncture group,three consecutive segments of the intervertebral discs(L2/3,L3/4,L4/5)were needled and modeled;in the endplate injection group,50 μL of anhydrous ethanol was injected at a single point on the endplates of the three consecutive segmental discs;in the combined group,three consecutive segmental intervertebral discs were needled and injected with 50 μL of anhydrous ethanol at four azimuthal points on the endplates of the corresponding segmental discs;and the blank control group received no interventions.X-ray examination was performed to measure the disc height index at 2,4,and 8 weeks after surgery.The intervertebral disc tissues were then taken for anatomical observation and pathological examination. RESULTS AND CONCLUSION:(1)Anatomical examination showed that fibrous annulus rupture,nucleus pulposus degeneration,and total disc structure disorder were the main manifestation in the acupuncture group,endplate injection group,and combined group,respectively.(2)X-ray examination showed that the disc height index showed the most obvious reduction in the acupuncture group at 2 weeks after operation,significant reductions in the endplate injection group at 2 and 4 weeks after operation,and significant reductions in the combined group at 2,4,and 8 weeks after operation.(3)Pathological examination showed that the fibrous ring structure was damaged and the inner annulus fibrosus protruded inward in the acupuncture group;endplate fissure,disordered arrangement and nucleus loss were observed in the endplate injection group;total disc structure disorder with the nucleus pulposus losing water and shrinking and no obvious border with the broken annulus fibrosus was found in the combined group.To conclude,acupuncture,endplate injection and the modified endplate injection method can establish the rabbit intervertebral disc degeneration model.Compared with the single method,the modified endplate injection method can greatly accelerate and aggravate the degeneration of the intervertebral disc,and can effectively shorten the experiment period.

BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.