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.

Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Coupled with the substantial workload, the clinical management of lung cancer is challenged by the critical need to efficiently and accurately process increasingly complex medical information. In recent years, large language models (LLMs) technology has undergone explosive development, demonstrating unique advantages in handling complex medical data by leveraging its powerful natural language processing capabilities, and its application value in the field of lung cancer diagnosis and treatment is continuously increasing. The paper systematically analyzes that the exceptional potential of LLMs in lung cancer auxiliary diagnosis, tumor feature extraction, automatic staging, progression/outcome analysis, treatment recommendations, medical documentation generation, and patient education. However, they face critical technical and ethical challenges including inconsistent performance in complex integrated decision-making (e.g., TNM staging, personalized treatment suggestions) and "black box" opacity issues, along with dilemmas such as training data biases, model hallucinations, data privacy concerns, and cross-lingual adaptation challenges ("data colonization"). Future directions should prioritize constructing high-quality multimodal corpora specific to lung cancer, developing interpretable and compliant specialized models, and achieving seamless integration with existing clinical workflows. Through dual drivers of technological innovation and ethical standardization, LLMs should be prudently advanced for holistic lung cancer management processes, ultimately promoting efficient, standardized, and personalized diagnosis and treatment practices.

BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

BACKGROUND:Currently,there are many modeling methods for pelvic organ prolapse animal models,and the commonly used methods are vaginal balloon dilatation,oophorectomy and the combination of the two.There is no study comparing the three modeling methods in detail.OBJECTIVE:To construct and validate a rat animal model of pelvic organ prolapse using three different methods and to identify the advantages and disadvantages of various models.METHODS:Seventy-two 8-week SPF-grade female Sprague-Dawley rats were selected and randomly divided into four groups,namely,vaginal balloon dilatation group,ovariectomy group,ovariectomy combined with vaginal balloon dilatation group(the combined group),and the sham-operated group(no ovariectomy and no vaginal dilatation).The vaginal wall tissues of rats were collected at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining,EVG staining and immunohistochemical staining of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 detection,and the pelvic floor muscle tissues were taken at 4,8 and 12 weeks after the operation for hematoxylin-eosin staining,Masson staining and EVG staining.RESULTS AND CONCLUSION:(1)Hematoxylin-eosi staining showed that there was no significant difference in the decrease of vaginal epithelial layer thickness in the vaginal balloon dilatation group compared with the sham-operated group,(P＞0.05),while the thickness of the vaginal epithelial layer was significantly reduced in the ovariectomy group and the ovariectomy combined with vaginal balloon dilation group(P＜0.001),and the reduction was more significant in the ovariectomy combined with vaginal balloon dilation group,remained stable at 8 weeks after surgery and lasted until 12 weeks.(2)The changes in the content of collagen fibers and elastic fibers in the vaginal wall stained by Masson and EVG staining were the same as the changes in the thickness of the vaginal epithelial layer stained by hematoxylin-eosin,and there were no changes in collagen fibers and elastic fibers in the pelvic floor muscle tissues of the treatment groups.(3)At 4,8 and 12 weeks after treatment,there was no significant difference in the expression levels of α-smooth muscle actin,Vimentin and matrix metalloproteinase 9 in the vaginal wall tissue of the balloon dilation group compared with the control group(P＞0.05),whereas the expression levels of α-smooth muscle actin and Vimentin were significantly decreased in the ovariectomy group and ovariectomy combined with vaginal balloon dilation group(P＜0.01)and the expression of matrix metalloproteinase 9 showed a significant increase(P＜0.01),with a more pronounced increase in the ovariectomy combined with vaginal balloon dilation group,and the increase reached a stable state at 8 weeks after surgery and could persist up to 12 weeks.To conclude,vaginal balloon dilatation could not maintain the degeneration of pelvic organ prolapse formed by the vaginal wall for a long period,and both ovariectomy and the combined method can be used.Ovariectomy combined with vaginal balloon dilatation can significantly accelerate and aggravate the formation of typical histological features of pelvic organ prolapse in vaginal wall tissues,effectively shorten the experimental period,and improve the efficiency.These effects reach a stable state at 8 weeks after surgery and can be sustained up to 12 weeks,which is practical and convenient for the study of pelvic organ prolapse animal models.

OBJECTIVE To explore the improvement effects of Suting pingchuan decoction （STPC） on bronchial asthma in rats and its potential mechanism. METHODS Male SD rats were randomly divided into blank group， model group， STPC low-， medium- and high-dose groups （4.14， 8.28， and 16.56 g/kg， respectively， based on the crude drug dosage）， and dexamethasone group （positive control， 1 mg/kg）， with 8 rats in each group. Except for the blank group， the other groups were sensitized by intraperitoneal injection of ovalbumin and challenged by nebulized inhalation of ovalbumin to establish a bronchial asthma model. From the day of nebulization challenge， rats of each group were administered the corresponding drug solution or normal saline by gavage 1 hour before aerosolization， once a day， for 7 consecutive days. During the experiment， behavioral changes in rats of each group were observed. After the last administration， the levels of inflammatory factors （interleukin-1β， interleukin-18） in bronchoalveolar lavage fluid （BALF）， and oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] in lung tissue were determined； pathological changes in lung tissue were observed； cell apoptosis in lung tissue， and the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） and the protein expressions of NLRP3， cleaved caspase-1， caspase-1， gasdermin D （GSDMD） and gasdermin D-N-terminal domain （GSDMD-N） in lung tissue were detected. RESULTS Compared with the blank group， rats in the model group showed symptoms such as scratching their ears and noses and frequent sneezing； the lung tissue structure was severely damaged， and there was obvious inflammatory cell infiltration. The levels of inflammatory factors in BALF， as well as the level of MDA， TUNEL-apoptotic cell rate， the mRNA expression of NLRP3， and the protein expressions of NLRP3， cleaved caspase-1， caspase-1， GSDMD-N and GSDMD in lung tissue were significantly increased or up-regulated， while the level of SOD in lung tissue was significantly decreased （ P ＜0.05 or P ＜0.01）. Compared with the model group， the above symptoms and pathological damages of lung tissue in each drug group were significantly improved， and all quantitative indicators （except for the protein expressions of GSDMD in the STPC groups， as well as the level of SOD， and the protein expressions of cleaved caspase-1， caspase-1 and GSDMD-N in the STPC low-dose group） were significantly reversed （ P ＜0.05 or P ＜0.01）. CONCLUSIONS STPC can improve airway inflammation and lung tissue damage in rats with bronchial asthma， reduce the level of oxidative stress， and decrease the release of inflammatory factors such as IL-1β and IL-18. Its mechanism of action may be related to the inhibition of pyroptosis activation mediated by the NLRP3/caspase-1/GSDMD signaling pathway.

OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

OBJECTIVE: To observe the effects of acupoint catgut embedding (ACE) on gut microbiota and fecal short-chain fatty acids (SCFAs) levels in patients with Parkinson's disease (PD) with constipation. METHODS: A total of 80 PD patients with constipation were randomly divided into an observation group and a control group, 40 cases in each group. Additionally, 40 healthy individuals were recruited as a healthy control group. The control group received conventional Western medical treatment for PD combined with polyethylene glycol (PEG), once daily for eight weeks. The observation group received additional ACE treatment at bilateral Tianshu (ST25), Zusanli (ST36), and Shangjuxu (ST37), once every two weeks for eight weeks. The healthy control group received no intervention. The spontaneous bowel movements (SBMs) per week and patient assessment of constipation quality of life (PAC-QOL) scores were assessed at baseline and after treatment in the two groups. Fecal samples were collected at the end of treatment for the observation and the control groups and at baseline for the healthy control group. Gut microbiota composition and diversity were analyzed using 16S rRNA method, and SCFA levels were measured using high-performance liquid chromatography (HPLC). RESULTS: Compared before treatment, the observation group showed a significant increase in SBMs (P<0.01), and PAC-QOL scores including physical discomfort, psychosocial discomfort, worry and concern, and total score were significantly reduced (P<0.01) after treatment; the control group also showed a reduction in PAC-QOL total score after treatment (P<0.01). After treatment, the observation group had significantly more SBMs (P<0.01), and lower PAC-QOL physical discomfort, psychosocial discomfort, worry and concern scores, and total score (P<0.01), and higher PAC-QOL satisfaction score (P<0.01) than the control group. Compared with the healthy control group, the control group showed decreased Chao1 and Ace indices (P<0.01). Compared with the healthy control group, the relative abundance of Prevotella and Roseburia was increased (P<0.05), while that of Enterobacter and Ruminococcus torques (six species in total) was decreased (P<0.05) in the control group. Compared with the control group, the observation group had increased relative abundance of Dialister, Parabacteroides, and Ruminococcus torques (P<0.05), and decreased relative abundance of Prevotella and Eubacterium ruminantium (P<0.05). Compared with the healthy control group, the control group had increased fecal SCFA levels (P<0.05); compared with the control group, the observation group had reduced fecal SCFA levels (P<0.05). Compared with the healthy control group, acetic acid, propionic acid, and butyric acid levels were elevated in the control group (P<0.05); compared with the control group, acetic acid, propionic acid, and butyric acid levels were decreased in the observation group (P<0.05). CONCLUSION ACE could increase spontaneous bowel movements and improve the quality of life in PD patients with constipation, which may be related to the regulation of gut microbiota composition and SCFA levels.
Humans ; Constipation/metabolism* ; Male ; Gastrointestinal Microbiome ; Acupuncture Points ; Female ; Middle Aged ; Parkinson Disease/complications* ; Aged ; Fatty Acids, Volatile/metabolism* ; Catgut ; Feces/microbiology* ; Acupuncture Therapy ; Quality of Life ; Adult