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.

Chronic post-surgical pain (CPSP) is a common long-term complication following lung surgery. Its high incidence significantly impacts patients’ quality of life and functional recovery, and imposes a substantial socioeconomic burden. This consensus aims to systematically establish a standardized integrated Chinese and Western medicine diagnostic and treatment framework for chronic post-lung surgery pain (CPLSP). Based on the latest domestic and international evidence-based medical research and multidisciplinary clinical experience, the working group comprehensively elaborates on core issues regarding CPLSP, including its definition, epidemiology, pathogenesis, clinical assessment, Western medical treatment, traditional Chinese medicine (TCM) treatment, and integrated strategies. The consensus emphasizes a patient-centered approach, adhering to the principles of multimodality, individualization, and stepwise management, highlighting the synergistic advantages of integrating Chinese and Western medicine throughout the entire perioperative management cycle encompassing "perioperative anti-inflammation, acute analgesia, and chronic rehabilitation." Through systematic literature retrieval and evidence integration, a total of 9 core recommendations were established to provide scientifically sound and clinically practical guidance.

ObjectiveTo establish a regional risk assessment system for hospital-acquired infections in neurosurgery department of general hospital, and to evaluate its prevention and control effectiveness. MethodsFailure mode and effect analysis (FMEA) was used to identify the core risk factors for infections in neurosurgery department. The risk priority number (RPN) of each risk factor was calculated to determine the priority intervention targets. Targeted interventions were developed and continuously refined through the plan-do-check-act (PDCA) cycles. Data from January to June 2023 (control group) and July to December 2023 (intervention group) were collected to compare the differences in environmental hygiene monitoring qualification rate, incidence rate of hospital-acquired infections among inpatients, and detection rate of bacterial antimicrobial resistance. ResultsHigh-risk factors for hospital-acquired infections in neurosurgery department included patient-related risk factors, inadequate implementation of isolation measures for special infections, and poor compliance with surgical site infection (SSI) prevention protocols. After intervention, the environmental hygiene qualification rate significantly increased from 81.55% to 100.00% (χ²=120.49, P<0.001). The overall hospital-acquired infection rate among inpatients decreased from 2.62% to 2.45%, the infection rate of per case declined from 3.12% to 2.84%, and the detection rate of multidrug-resistant organism infections reduced from 43.72% to 36.79%. Additionally, antimicrobial utilization rate decreased from 48.75% to 42.53% (χ²=34.09, P<0.001). ConclusionThe FMEA-based risk assessment system can effectively identify critical infection risks in neurosurgery department, and targeted interventions can significantly improve infection prevention and control performance.

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe （N2FBR） in idiopathic pulmonary fibrosis （IPF）， focusing on its effects on endoplasmic reticulum （ER） stress， apoptosis， stemness maintenance， and regenerative capacity of alveolar type Ⅱ epithelial cells （AT2 cells）， and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin （BLM）. Mice were randomly divided into blank control， model， low-， and high-dose N2FBR intervention groups （9.1， 18.2 g·kg^-1）， and prednisolone intervention group （6.5 mg·kg^-1）. Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin （HE） and Masson's trichrome staining. Hydroxyproline （HYP） content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors， including collagen type Ⅰ alpha 1 chain （ColIa1）， alpha-smooth muscle actin （α-SMA）， and tissue inhibitor of metalloproteinase 1 （Timp1）， were detected by real-time polymerase chain reaction （Real-time PCR）. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C （SPC） and cysteine-aspartic protease-3 （Caspase-3）. Endoplasmic reticulum （ER） stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase （PERK）. Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy （TEM）. The expression levels of key proteins involved in ER stress and apoptosis pathways， including PERK， activating transcription factor 4 （ATF4）， and Caspase-3， were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen （Ki-67） was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology （labeling AT2 cells with GFP） combined with Krt8 labeling was used to evaluate intermediate differentiation states， and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells （AT1） was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue， increased collagen deposition， elevated lung coefficient， decreased pulmonary function， and upregulation of fibrosis-related factors （P<0.01）. High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction， significantly reduced HYP content （P<0.01）， and significantly downregulated ColIa1， α-SMA， and Timp1 expression （P<0.01）. Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group， which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group， which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group， which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4， as well as the apoptosis-related protein Caspase-3， were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group， which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells， the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group （P<0.01）. Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive （Krt8⁺GFP⁺） cells increased in the model group， indicating differentiation arrest. This proportion was significantly reduced in the treatment group， and the morphology of GFP⁺ cells exhibited a flattened， extended shape， suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells， reduces AT2 cell apoptosis， restores lamellar body structure and function， enhances proliferation activity， and alleviates differentiation arrest to promote differentiation into AT1 cells， thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi， harmonizing Qi and blood， and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells， providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.

Objective To investigate the factors affecting the distribution of Pomacea and project the trends in the spread of suitable distribution areas of Pomacea in 2050 and 2070 in Dali Bai Autonomous Prefecture, so as to provide insights into Pomacea control in the prefecture. Methods The longitudes and latitudes of Pomacea sampling sites were captured based on Pomacea field survey data in 12 cities (counties) of Dali Bai Autonomous Prefecture from 2023 to 2024. A total of 19 climatic factors (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest month, mean temperature of the coldest month, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, mean temperature of the warmest quarter, and mean temperature of the coldest quarter) and representative concentration pathways (RCPs) were retrieved from the world climate database (www.worldclim.org). All climatic variables were employed to create a maximum entropy (MaxEnt) model. The predictive accuracy of the model was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), and the contributions of these 19 climatic factors to the distribution of Pomacea were analyzed in Dali Bai Autonomous Prefecture using Jackknife test. In addition, the suitable distribution areas of Pomacea were predicted with the MaxEnt model in Dali Bai Autonomous Prefecture in 2024 and in 2050 and 2070 under RCP4.5. Results Data pertaining to 91 Pomacea sampling sites were captured. ROC analysis revealed the MaxEnt model had an AUC value of 0.885 ± 0.088 for predicting the suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture. Of the 19 climatic factors, the maximum temperature of the warmest month had the highest contribution to the distribution of Pomacea in Dali Bai Autonomous Prefecture, followed by mean temperature of the driest quarter, mean temperature of the wettest quarter and minimum temperature of the coldest month. The suitable distribution area of Pomacea was predicted to be 14 555.69 km² in Dali Bai Autonomous Prefecture in 2024, and would expand gradually to the southeastern part of the prefecture in the future due to climatic factors. The suitable distribution areas of Pomacea were projected to expand to 21 475.61 km² in 2050 and 25 782.52 km² in 2070 in Dali Bai Autonomous Prefecture, respectively. Conclusions Temperature is an important contributor to the distribution of Pomacea in Dali Bai Autonomous Prefecture, and the suitable distribution area of Pomacea will gradually expand to the southeastern part of the prefecture in 2050 and 2070.

Pancreatic cancer is currently recognized as one of the most malignant solid tumors， with a 5-year survival rate of 13% over a long period of time， and 80% of the patients have lost the opportunity for surgery at the time of confirmed diagnosis. In addition， the efficacy of conventional radiochemotherapy and targeted therapy is limited by high tumor heterogeneity and the complex immunosuppressive microenvironment. In recent years， mRNA vaccines have become a new focus of tumor immunotherapy due to their unique technical advantages. Based on non-integrating mRNA templates， mRNA vaccines enable precise encoding of tumor neoantigens， which are efficiently expressed in the host and can induce multifaceted immune responses. As for pancreatic cancer， current studies mainly focus on the development and optimization of tumor-associated antigen vaccines and tumor-specific antigen vaccines， as well as next-generation sequencing-guided neoantigen epitope optimization， innovative targeted delivery systems， and artificial intelligence-powered predictive models for immune response， thereby promoting the application of mRNA vaccines in the precise treatment of pancreatic cancer. Further studies should make breakthroughs in the targeted blockade of critical immunosuppressive molecules within the tumor microenvironment， the precise identification of tumor-specific antigenic epitopes， and the development of highly efficient vaccines， so as to bring new hopes for patients with pancreatic cancer.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.