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 quantitatively assess the health risk of preservatives from beverages around primary schools in Anshun City, and to provide scientific basis for precise food safety supervision. Methods: From December 2023 to July 2024, 602 beverage samples were randomly collected from within 100 meters of 19 primary schools in Anshun City. The content of benzoic acid, sorbic acid, and dehydroacetic acid was detected according to GB 5009 series standards. Combined with children s physiological parameters (body weight 30 kg, daily intake 0.15 L), the Hazard Quotient (HQ) and Hazard Index (HI) models were used to evaluate health risks. Results: The total detection rate of preservatives from beverages around primary schools was 63.0%, and the total over limit rate was 9.0%. The detection rate of preservatives in flavored beverages was the highest (72.6%), and the highest over limit rate of preservatives in special purpose beverages was the highest (17.2%). The single preservative HQ (benzoic acid up to 0.47 ) and mixed HI (up to 0.55) of all samples were below 1(safety threshold). However, the HQ value of benzoic acid in flavored beverages (0.47) was 2.9 times that of sorbic acid (0.16), contributing significantly to health risk. Sensitivity analysis showed that if the daily consumption increased to 0.3 L, the HI value of flavored beverages would rise to 1.11, exceeding the safety threshold. Enterprise scale analysis showed that the exceedance rate of special purpose beverages in large enterprises reached 30.0%, while micro enterprises, accounting for a dominant market share (52.2%), constituted the main source of children s daily exposure to their products. Conclusions The overall health risk of perservatives in beverages sold near primary schools in Anshun City is controllable, but there is a noticeable risk of gradient. The risk of children’s exposure to preservatives through beverage consumption should not be ignored.

Objective To explore the feasibility of using high-definition thoracoscopy to identify sympathetic ganglia during thoracic sympathicotomy for primary palmar hyperhidrosis. Methods The clinical data of patients with primary palmar hyperhidrosis who underwent high-definition thoracoscopic sympathicotomy in Taikang Xianlin Drum Tower Hospital from June to July 2023 were retrospectively analyzed. Intraoperative visualization rates and anatomical variations of sympathetic ganglia were recorded, and the consistency between white-light thoracoscopy and near-infrared fluorescence imaging was compared. Additionally, surgical videos from previous fluorescence-guided procedures were reviewed. Results Finally 100 patients were collected, including 54 females and 46 males, with an average age of (21.92±6.56) years. All patients underwent endoscopic thoracic sympathicotomy at R3 level. The overall intraoperative ganglion visualization rate was 92.5% (740/800), with G2-G5 rates of 95.5% (191/200), 94.0% (188/200), 94.0% (188/200), and 86.5% (173/200), respectively. Ganglion variations occurred in 32.0% (237/740), predominantly at G3 (29.8%) and G4 (42.6%). In 5 indocyanine green-enhanced patients, the concordance rate between white-light and near-infrared fluorescence imaging was 100.0% (38/38). Video analysis of 14 near-infrared fluorescence-guided surgeries demonstrated a 99.1% (107/108) consistency rate. Postoperative palmar hyperhidrosis improvement reached 100.0% (100/100) with no Horner’s syndrome. Conclusion With the wide clinical application of high-definition thoracoscopy, accurate thoracic sympathicotomy has the feasibility of clinical application.

Objective: To provide evidence for improving emergency blood supply protocols by analyzing the clinical characteristics and disease distribution of emergency transfusion patients, especially those receiving≥10 units of red blood cells (RBCs). Methods: The data of 4 157 patients who urgently applied for large-volume blood transfusion in various hospitals in Shanghai from May 2024 to April 2025 were selected and analyzed statistically. Results: Tertiary gradeA hospitals accounted for the largest proportion of total transfusion volume (U) (48.79%, 8 420/17 256.5), with no statistically significant differences in RBC transfusion volumes among hospitals of different grades (P>0.05). All blood products are most widely used in tertiary hospitals. Obstetric blood transfusion (U)(19.07%, 3 277.5/17 190.5) was the most frequent. A-mong the hospitals of patients who received emergency blood transfusion with red blood cell suspension≥10 U, tertiary gradeA hospitals also had the largest transfusion volume (U)(47.19%, 1 107/2 346). In terms of disease types, the top three diseases in terms of blood transfusion volume (U) were obstetric transfusion (24.59%, 572/2 326), digestive diseases (14.53%, 338/2 326) and tumors (14.19%, 330/2 326). Conclusion: Tertiary grade A hospitals are the main demand units for emergency blood transfusion, with pregnant women and cancer patients being the core blood-using groups. It is suggested that the safety, timeliness and sufficiency of emergency blood transfusion be guaranteed by establishing a hierarchical blood supply mechanism, formulating single-disease blood transfusion plans and promoting precise blood transfusion guided by thromboelastography.

Renal lymphatic vessel density is clinically relevant in kidney disease but is still assessed by slow, subjective visual estimation. We evaluated a weakly supervised, attention-based multiple-instance learning framework for automated detection and quantification of renal lymphatic vessel density on D2-40-stained whole-slide images (WSIs). Methods: Two independent internal datasets from Tongji Hospital were collected, including 198 cases of chronic kidney disease (CKD) and 50 cases of hypertensive nephropathy (HTN). All biopsies were immunohistochemically stained for D2-40 and digitized as WSIs. Pathologists provided only slide-level labels (D2-40 high vs. D2-40 low). Tissue regions were automatically segmented, tiled into patches, and encoded using a pretrained convolutional neural network. Patch embeddings were then analyzed with a clustering-constrained attention multiple-instance learning (CLAM) model. Unlike conventional multiple-instance learning (MIL) methods that only weight instances, CLAM jointly performs attention-based instance selection and instance-level clustering to distinguish positive from negative evidence within each slide, yielding more discriminative slide-level features and interpretable attention maps. Performance was compared with a classic MIL model trained on the same features. Results: CLAM achieved area under the receiver operating characteristic curves of 0.942 and 0.858 on the CKD and HTN datasets, respectively, outperforming classic MIL (0.866 and 0.801). Attention maps highlighted lymphatic-rich regions consistent with renal pathologists’ assessments. Conclusions: This clustering-constrained, attention-based weakly supervised framework enables fully automated, reproducible quantification of renal lymphatic vessel density from WSIs, providing renal pathologists with rapid visual and numerical support for diagnosis and risk stratification in CKD and HTN.

Pancreatic ductal adenocarcinoma （PDAC） has an extremely poor prognosis， and resistance to gemcitabine is one of the key reasons for treatment failure， with an underlying mechanism closely associated with lipid metabolic reprogramming in tumor cells. This article aims to systematically elaborate on the multidimensional drug resistance network constructed by such reprogramming and the feasibility of targeted intervention. Lipid metabolic reprogramming comprehensively remodels the metabolic homeostasis of PDAC cells by enhancing lipid uptake， de novo synthesis， storage， and oxidative catabolism in a synergistic manner. This process alters membrane lipid composition to impede drug influx and promote efflux， thereby reducing intracellular drug concentration. Meanwhile， it activates pathways involving sterol regulatory element-binding protein and peroxisome proliferator-activated receptor δ， couples lipid synthesis with cell survival， stemness， and anti-apoptotic capacity， and synergizes with autophagy to provide survival support through “lipophagy”. In addition， it reshapes the tumor microenvironment through “lipid hijacking” and the secretion of immunosuppressive mediators. Based on the above mechanisms， targeting key lipid metabolic enzymes （such as fatty acid synthase， stearoyl-CoA desaturase， carnitine palmitoyltransferase 1） or their upstream regulators has shown certain potential in reversing such drug resistance in preclinical studies. Although clinical translation faces the challenges such as systemic toxicity， metabolic redundancy in tumors， and patient heterogeneity， the development of biomarkers， intelligent drug delivery systems， and combined therapies may provide new ideas for overcoming drug resistance.

BACKGROUND:The reasonable implantation range of femoral prosthesis in unicompartmental knee arthroplasty in patients with osteoporosis has not been investigated,and previous studies have often been based on unicompartmental knee arthroplasty models in normal bone,with fewer mechanical studies in models with non-normal bone.Complications after unicompartmental knee arthroplasty have been shown to be highly associated with osteoporosis. OBJECTIVE:To analyze the biomechanical effects of the coronal inclination of the Sled fixed platform femoral prosthesis on unicompartmental knee arthroplasty in patients with osteoporosis and to find the correlation between osteoporosis and mid-and long-term complications after unicompartmental knee arthroplasty. METHODS:Based on the digital imaging technology to obtain the data of the knee joint and prosthesis,a normal bone knee model is then created by using specialized software such as Mimics and Geomagic studio.Based on a validated normal bone knee model,an osteoporotic knee model was created by changing the material parameters.Totally 14 unicompartmental knee arthroplasty finite element models were created using Sled fixed platform femoral prosthesis:standard position(0°),varus and valgus angles:3°,6°,9° in the normal bone and osteoporosis groups.Stress changes on the surface of polyethylene liner,cancellous bone under tibial prosthesis,and cortical bone were calculated and analyzed in all unicompartmental knee arthroplasty models. RESULTS AND CONCLUSION:(1)In the osteoporotic models,the high stress values of the polyethylene liner surface and the cancellous bone under the tibial prosthesis increased with the increase of the tilt angle of the femoral prosthesis,and the high stress values of the cortical bone surface under the tibial prosthesis increased with the increase of the prosthesis valgus angles and decreased with the increase of the varus angles.(2)For the polyethylene liner surface as well as the subcortical bone surface of the tibial prosthesis,the high stress values of the models for each inclination angle in the osteoporosis group were greater than those of the corresponding models in the normal bone group.For the surface of the cancellous bone under the tibial prosthesis,the high stress values of the tilt angle models of the osteoporosis groups were smaller than those of the normal bone groups.(3)Osteoporosis may cause biomechanical abnormalities in the internal structures of the knee after unicondylar replacement,increasing the potential risk of postoperative aseptic loosening of the prosthesis and periprosthetic fractures.Varus and valgus of the femoral prosthesis in the coronal plane should be avoided as much as possible when performing medial unicompartmental knee arthroplasty with a Sled fixation platform in osteoporotic knees.

ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective:To investigate the efficacy of enteral nutrition combined with trocar puncture with a sump drain in the treatment of Crohn's disease(CD)complicated by intra-abdominal abscess.Methods:A descriptive case series study was conducted.Clinical data of CD patients with intra-abdominal abscess who received enteral nutrition and trocar puncture with a sump drain at the Intestinal Fistula and Intra-abdominal Infection Center of Nanjing BenQ Hospital between June 2018 and December 2022 were retrospectively collected.Laboratory parameters,including white blood cell(WBC)count,C-reactive protein(CRP),and procalcitonin(PCT),were recorded at baseline(pre-puncture)and on days 1,3,and 7 post-puncture.Changes in clinical indicators before and after intervention were compared.Results:All 19 CD patients with intra-abdominal abscess successfully underwent CT-guided trocar puncture with a sump drain,with fistulography confirming the presence of intestinal fistula.No post-procedural complications,including puncture site infection,new-onset intestinal fistula or intra-abdominal hemorrhage,were observed.The median treatment duration was 58.3 days(range:14～300 days).10 patients achieved spontaneous healing while 9 eventually underwent surgical intervention for unresolved fistulas.Post-puncture WBC levels decreased significantly on days 1,3,and 7 compared to baseline(P<0.05).Serum CRP levels increased markedly on day 1 post-puncture(P<0.05)but declined significantly by days 3 and 7(P<0.05).No statistically significant difference was observed in serum procalcitonin levels before and after puncture(P>0.05).Conclusion:The combination of enteral nutrition and trocar puncture with a sump drain is safe,feasible,and effective for managing CD complicated by intra-abdominal abscess.