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.

As a cheap and effective antibiotic,sulfonamides are often used in animal husbandry.However,their residues in animal-derived foodstuffs will threaten human health.Consequently,a high-performance liquid chromatography(HPLC)method integrated with supramolecular solvent microextraction was successfully established for simultaneous quantification of sulfonamide residues sulfachlorpyridazine,sulfamethoxazole,sulfamethoxypyridazine and sulfadimethoxine in milk matrices.This approach exhibited prominent characteristics of operational simplicity,environmental sustainability,and high extraction efficiency.The supramolecular solvents prepared by tributyl octylphosphine tetrafluoroborate and tetrahydrofuran were employed as extraction solvents.The analytes underwent isolation and concentration via dispersive liquid-liquid microextraction(DLLME)prior to quantitative determination using high-performance liquid chromatography(HPLC).The composition and microscopic morphology of the supramolecular solvent were characterized through a series of analytical techniques,including phase diagram,Fourier transform infrared spectroscopy,scanning electron microscopy,and inverted fluorescence microscopy and so on.The density and pH value of supramolecular solvents were determined.The extraction conditions were optimized through the one-factor experiments.The experimental results demonstrated that under the optimal extraction conditions,the four kinds of sulfonamide antibiotics exhibited excellent linearity within respective detection range(R2 ≥ 0.9998)and the limits of detection(LOD)were 0.67-1.45 μg/L.Compared with literature methods,this approach offered some advantages such as simplicity of operation and less reagent consumption,and could be used for analysis and detection of sulfonamide antibiotic residues in milk samples.The present method provided technical support for food safety regulation and paved a new way for the application of supramolecular solvents in the field of extraction and separation.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective:To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria (PNH) and evaluate their association with clinical manifestations.Methods:This study enrolled patients with PNH, who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023. The clinical information of participants was retrospectively recorded, and peripheral blood samples were collected. Gender- and age-matched normal controls (NC) were recruited accordingly. C5b-9, C3, C4b, and factor B (FB) deposition levels on peripheral red blood cells, white blood cells, and platelets were detected with flow cytometry. The correlation between complement deposition levels and clinical symptoms was analyzed.Results:This study involved 73 patients with PNH, including 42 (57.5%) males, with a median age of 36 (range: 14-76) years. 16 matched NC were collected. Among patients with PNH, 36 (49.3%) had classical PNH and 37 (50.7%) had aplastic anemia-PNH syndrome. Thromboembolic events (TEE) occurred in 18 (24.7%) patients. The median HGB, absolute reticulocyte count (Ret), and lactate dehydrogenase of PNH patients were 76 (37-116) g/L, 181.0 (45.9-495.8) ×10 9/L, and 1 875 (377 - 5 509) U/L, respectively. The median number of Flaer-negative white blood cells was 94.0% (13.0% - 99.9%) ; the median CD59 negative red blood cells was 46.7% (9.0% - 93.0%). The deposition of C5b-9, C3, C4b, and FB on red blood cells, white blood cells, and platelets in patients with PNH was significantly higher than that in NC (all P<0.05). C5b-9 deposition level was significantly higher than that of C3, C4b, and FB on all three blood cell lineages in PNH patients (all P<0.01). The deposition of all complement fragments on red blood cells was significantly lower than that on white blood cells and platelets (all P<0.01). C5b-9 deposition on red blood cells was positively correlated with Ret in PNH patients ( P=0.005). C3 ( P=0.001) and C4b ( P=0.017) deposition levels on white blood cells and C3 deposition on platelets ( P=0.002) in patients with TEE history were lower than those without. Conclusions:C5b-9, C3, C4b, and FB deposition levels on all three blood cells in patients with PNH were higher than NC. Increased C5b-9 on red blood cells may indicate active hemolysis. Reduced C3 and C4b levels on white blood cells and low C3 deposition on platelets may indicate TEE risk.

Objective:To evaluate the efficacy and safety of luspatercept combined with roxadustat in patients with refractory low-risk myelodysplastic neoplasms with ring sideroblasts (MDS-RS) patients.Methods:In this single-center, prospective, randomized controlled trial, patients with refractory MDS-RS were randomly assigned in a 1:2 ratio to receive either combination therapy (luspatercept + roxadustat) or luspatercept monotherapy. The primary endpoint was erythroid response at 12 weeks, while secondary endpoints included erythroid response at 24 weeks, achievement of transfusion independence ≥8 weeks within the first 12 weeks, and other hematologic indicators.Results:The combination therapy and monotherapy groups included 16 and 32 patients, respectively. Baseline demographic characteristics, laboratory tests, IPSS-R risk classification, transfusion burden, EPO levels, and previous treatment history were comparable between the two groups ( P>0.05). With similar doses of luspatercept and follow-up durations, no significant differences were observed between the groups at either 12 or 24 weeks in terms of erythroid response, transfusion independence, or other clinical indicators (all P-values>0.05). The incidence of adverse events was similar in both groups (all P-values>0.05) . Conclusion:Luspatercept combined with roxadustat shows comparable efficacy and safety to luspatercept monotherapy in the treatment of refractory low-risk MDS-RS. Clinical trial register: Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing (K3697)

Objective:To investigate the relationship between serum endothelia cell-specific molecules (endocan), 8-hydroxy-2′deoxyguanosine (8-OHdG) and restless legs syndrome (RLS) in patients with end-stage renal disease (ESRD) on hemodialysis.Methods:A total of 180 ESRD hemodialysis patients admitted to the Shenyang First People′s Hospital, the Liaoning Electric Power Center Hospital and the Northern Theater Command General Hospital of the Chinese People′s Liberation Army from May 2021 to May 2023 were prospectively selected and divided into RLS group (41 cases) and non-RLS group (139 cases) according to whether RLS occurred. According to the International RLS Rating Scale (IRLS), the patients with RLS were divided into mild group (12 cases), moderate group (19 cases) and severe group (10 cases). Serum endocan and 8-OHdG levels were detected by enzyme-linked immunosorbent assay. Pearson correlation was used to analyze the correlation between serum endocan, 8-OHdG levels and IRLS scores in RLS patients. Multivariate logistic regression model was used to evaluate the influencing factors of RLS in ESRD hemodialysis patients. The diagnostic value of serum endocan and 8-OHdG levels in ESRD hemodialysis patients was analyzed by receiver operating characteristic (ROC) curve.Results:Comparing with the non-RLS group [(4.03±1.23)ng/ml, (0.38±0.13)ng/ml], the levels of serum endocan in the RLS group [(6.10±1.95)ng/ml], 8-OHdG [(0.53±0.14)ng/ml] were higher ( t=8.180, 6.379, P<0.001). The levels of serum endocan of the RLS patients in the mild, moderate and severe groups [(3.61±1.01)ng/ml, (6.39±1.41)ng/ml, (8.54±2.68)ng/ml], 8-OHdG [(0.39±0.07)ng/ml, (0.51±0.05)ng/ml, (0.74±0.08)ng/ml] were increased successively ( F=23.065, 83.013, P<0.001). Pearson correlation analysis showed that serum endocan and 8-OHdG levels were positively correlated with IRLS scores in RLS patients ( r=0.813, 0.830, P<0.001). Multivariate logistic regression analysis showed that long dialysis time, elevated serum endocan and 8-OHdG were independent risk factors for RLS in ESRD hemodialysis patients, and elevated ferritin was independent protective factor (all P<0.05). ROC curve analysis showed that the area under the curve of RLS in ESRD hemodialysis patients diagnosed with serum endocan and 8-OHdG combined was 0.919 (95% CI: 0.870-0.955), which was larger than in patients diagnosed with serum endocan and 8-OHdG alone 0.791 (95% CI: 0.724-0.848), 0.780 (95% CI: 0.712-0.838). Conclusions:The increase of serum endocan and 8-OHdG is related to the occurrence and severity of RLS in ESRD hemodialysis patients. The combined detection of serum endocan and 8-OHdG levels is of high diagnostic value in the occurrence of RLS in ESRD hemodialysis patients.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

The incidence of non-alcoholic fatty liver disease(NAFLD)has been increasing annually.Current primary treatment strategies involve dietary modifications and increased physical activity to allevi-ate symptoms,yet there is a notable lack of targeted pharmacological interventions.Members of the micro RNA-29(miR-29)family(miR-29a,miR-29b,miR-29c)are known to play a critical regulatory role in lipid metabolism within hepatocytes;however,the underlying mechanisms remain to be elucidated.This study aims to identify the target genes and associated signaling pathways of the miR-29 family,thereby providing potential therapeutic targets for the development of NAFLD treatments.Firstly,the human liver cell line HepG2 was utilized as a model for adipogenic induction,and miR-29a/b/c-3p mimics were indi-vidually transfected.Through methods such as Oil Red O staining and triglyceride(TG)quantification,it was observed that the miR-29 family members significantly inhibited lipid accumulation in hepatocytes(P＜0.05).Subsequently,qRT-PCR and Western blot were utilized to detect the expression levels of ad-ipogenic marker genes(fatty acid synthase(FAS),acetyl coa carboxylase(ACACA),stearoyl-coen-zyme a desaturase 1(Scd 1))and autophagy marker genes(sequestosome 1(SQSTM1,also known as p62),autophagy related gene 5(Atg5)),and the results indicated that the members of the miR-29 fam-ily could significantly suppress the expression of FAS,ACACA,Scd1,and p62 genes in hepatocytes,while significantly enhancing the level of the Atg5 gene.Further investigations using signaling pathway activity analysis and dual luciferase reporter assays confirmed that the miR-29a/b/c could suppress the mTOR signaling pathway activity and directly interact with the ten-eleven translocation 2(TET2)gene.Finally,co-transfection experiments were performed to examine the potential synergistic effects among the miR-29-3p family members,and the results demonstrated that co-transfection of miR-29 family members more effectively inhibited lipid droplet accumulation in HepG2 cells and further suppressed the expression of the target gene TET2 compared to individual transfection.In summary,the miR-29 family members may reduce lipid accumulation in hepatocytes by inhibiting the mTOR signaling pathway via the TET2 gene,and they exhibit a positive synergistic effect.

Objective:To analyze the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with main splenic artery embolization in the treatment of patients with portal hypertension upper gastrointestinal bleeding complicated with extensive portal vein thrombosis (PVT).Methods:This study was a prospective, single-center, open-label, single-arm clinical trial. In the first phase, 81 patients with portal hypertension upper gastrointestinal bleeding who were admitted to Beijing Shijitan Hospital, Capital Medical University from January 2018 to December 2018 were consecutively enrolled, including 57 males and 24 females, with the age of (51.3±10.4) years. During TIPS surgery, the pressure of the portal vein before and after the balloon blocking the splenic artery was measured to clarify the contribution of the splenic artery to portal hypertension. In the second stage, from January 2019 to December 2022, 104 patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT were re-enrolled, including 71 males and 33 females, with the age of (50.9±12.5) years. TIPS combined with main splenic artery embolization was performed, and portal vein pressure was measured before and after embolization. Follow up on the postoperative esophageal and gastric varices of the patients in the second stage.Results:The portal vein pressures before and after the first stage of balloon occlusion of the splenic artery were (35.2±8.4) mmHg (1 mmHg=0.133 kPa) and (24.2±6.3) mmHg, respectively. The pressure after occlusion was lower than that before occlusion, and the difference was statistically significant ( t=10.54, P<0.001). The portal vein pressures before and after the second stage embolization were (36.1±9.5) mmHg and (21.1±4.7) mmHg respectively. The pressure after embolization was lower than that before embolization, and the difference was statistically significant ( t=13.47, P<0.001). In the second stage, among the 104 patients, the proportion of those whose varicose veins disappeared or improved 6 months after the operation was 43.3%(45/104) and 51.0%(53/104), respectively. There were no patients with aggravation or rebleeding due to rupture. One year later, 8 patients (7.7%) had aggravated or ruptured esophageal and gastric varices with bleeding. Two years later, 12 patients (11.5%) had aggravated or bleeding. Conclusion:TIPS combined with main splenic artery embolization can effectively reduce the portal vein pressure in patients with portal hypertension upper gastrointestinal bleeding complicated with extensive PVT, improve the degree of esophageal and gastric varices, and reduce the risk of gastrointestinal bleeding.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.