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.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

OBJECTIVE To analyze the blood components of Suanzaoren Decoction after oral administration using UHPLC-Q Exactive Orbitrap-MS technology.METHODS Female Sprague-Dawley(SD)rats were used as experimental subjects,and Suanza-oren Decoction was administered orally.Serum samples were collected,and the aqueous extract of Suanzaoren Decoction and the serum were analyzed using UHPLC-Q Exactive Orbitrap-MS technology to identify the prototype components and metabolites absorbed into the blood by comparing and analyzing with the LuMet-TCM database.RESULTS It showed that a total of 458 components were iden-tified in the aqueous extract of Suanzaoren Decoction,and 26 chemical components were identified in the blood,including 23 prototype components and 3 metabolites.CONCLUSION The prototype components absorbed into the blood discovered in this study may be the active ingredients of Suanzaoren Decoction,providing a reference for the research on the pharmacodynamic material basis of Suanza-oren Decoction.

Objective:To construct an evaluation system for the risk factors of PICC catheter malposition in patients with hematological diseases, providing a reference for the prevention of central venous access malposition in these patients.Methods:From July 2022, a literature review was conducted to retrieve literature published in database and website such as PubMed, Web of Science domestically and internationally related to the risk assessment system of PICC catheter malposition in hematology patients. After full-text screening and extraction, the articles were included in the system′s item pool. Through further discussions among the research group′s experts, in conjunction with evidence-based findings, the system′s consultation items were formulated. Using the Delphi expert consultation method, a standard for PICC catheter malposition risk assessment system applicable to hematology patients was ultimately formulated.Results:In this study, 25 experts were invited for consultation: 24 females and 1 male, with an average age of (48.36 ± 6.82) years. After two rounds of expert consultations and revisions, the risk factors for PICC catheter malposition in hematology patients were identified to include 4 first-level indicators: patient factors, treatment factors, catheter-related factors, and operational factors, along with 11 second-level indicators and 25 third-level indicators. The positive coefficients of the experts in the two rounds of consultations were 84% and 100%, respectively; the Kendall coordination coefficients were 0.22 and 0.55 (both P<0.05); and the expert authority coefficient was 0.93. Conclusions:The risk assessment scale for PICC catheter malposition in patients with hematological diseases has high expert recognition and good consistency, and has clinical practice and guiding value.

Diabetic encephalopathy(DE)is a complication of the central nervous system induced by diabetes,characterized by insidious onset and complex pathological mechanisms.Recent research has revealed that the pathological mechanisms of DE are closely associated with the imbalance of intercellular communica-tion across multiple organs.Exosomes,serving as vital media-tors of intercellular communication,are involved in the patholog-ical progression of DE and hold promise as diagnostic biomarkers and therapeutic targets for DE.Traditional Chinese medicine(TCM)can improve communication between brain cells and be-tween peripheral and brain tissues by regulating exosomes and their contents,thereby preventing and treating DE.Meanwhile,exosomes,as targeted delivery carriers of active molecules,can carry TCM monomers more easily across the blood-brain barrier to prevent and treat DE.In light of this,this review summarizes the regulatory role of exosomes in the pathological progression of DE and explores the enormous potential of TCM in the preven-tion and treatment of DE by regulating exosomes and using exo-somes as traditional Chinese medicine carriers,aiming to pro-vide new evidence for the prevention and treatment of DE with TCM.

Objective:To evaluate the feasibility and safety of open ventilation masks in patients with proliferative diabetic retinopathy (PDR) undergoing vitrectomy under local anesthesia.Methods:A randomized clinical trial was conducted.Eighty PDR patients (80 eyes) undergoing vitrectomy with local anesthesia were enrolled at Xuzhou Municipal Hospital from May to July 2024.Patients were randomly divided into an experimental group and a control group using a random number table method, with 40 cases (40 eyes) in each group.The experimental group received oxygen through an ophthalmic surgical open ventilation mask during the operation, while the control group used a traditional nasal cannula.The respiratory rate, heart rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation before and after oxygen inhalation during the operation were compared between the two groups.Patient comfort level, airway patency, anxiety status, satisfaction level, operation time, surgical success rate, and incidence of intraoperative complications were also compared.This study adhered to the Declaration of Helsinki and the study protocol was appreed by the Ethics Committee of Xuzhou Municipal Hospital (No.2024-KY-065).Results:After oxygen inhalation during the operation, improvements in respiratory rate, heart rate, and oxygen saturation were greater in the experimental group than in the control group, with statistically significant differences ( t=4.671, 7.894, 1.588; all P<0.05).The Borg, and Hamilton Anxiety Scale scores were lower in the experimental group than in the control group, with statistically significant differences ( t=2.828, 4.880; both P<0.05), while the Bruggrmann Comfort Scale score was higher than that in the control group ( t=2.774, P<0.05).There were no statistically significant differences in operation time, surgical success rate or incidence of complications between the two groups ( t=0.595, P=0.554; χ2=0.346, 0.263; both P>0.05).Satisfaction rate of patients in the experimental group was 97.5%(39/40), which was higher than 85.0%(34/40) in the control group, with a statistically significant difference ( χ2=3.914, P=0.048). Conclusions:For PDR patients undergoing vitreous surgery under local anesthesia, using an ophthalmic surgical open ventilation mask for oxygen inhalation can effectively enhance respiratory comfort level, alleviate anxiety, maintain stable vital signs, improve overall comfort level, and ensure smooth surgery, without observed adverse reactions related to mask use, which makes it worthy of clinical promotion and application.

Objective:To systematically evaluate the qualitative studies on the experience of role transition among caregivers of patients with young-onset dementia.Methods:A computer-based search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for qualitative studies on the experience of role transition among caregivers of patients with young-onset dementia. The retrieval time limit was from the establishment of the database to May 2024. The quality of the literature was evaluated by using the quality evaluation criteria of the Evidence-Based Health Care Center of the Joanna Briggs Institute, and the Meta-synthesis of the results was carried out by using the pooling integration method.Results:A total of 14 articles were included, 46 results were extracted, and nine categories were formed by induction. Three integration results were comprehensively obtained, namely, individuals and families were troubled by multiple problems, there was a strong demand for role support during the transition period, and positive coping led to role growth.Conclusions:Caregivers of patients with young-onset dementia have multiple problems and diverse care needs during the role transition period, and positive coping in this process can lead to role growth.

Objective:To compare the therapeutic efficacy and safety of local anesthesia and spinal anesthesia for the patients with varicocele(VC)who underwent microsurgical varicocelectomy(MV).Methods:We retrospectively analyzed the data of VC patients who underwent MV treatment at the Andrology Department of the Affiliated Ruikang Hospital of Guangxi University of Chinese Medicine from May 2020 to March 2023.Cases with complete clinical data and follow-up evaluation were selected and divided into a control group(spinal anesthesia)and an observation group(local anesthesia)according to different anesthesia methods.The surgical time(including anesthesia time),visual analogue scale(VAS)score for pain,hospital stay,treatment cost,sperm concentration,for-ward motile sperm rate,and normal sperm morphology rate after three months of surgery,as well as postoperative complications and re-currence rate were compared between the two groups.Results:A total of 107 eligible cases were included,with 56 cases in the con-trol group and 51 cases in the observation group.There was no significant difference in the VAS score for pain during and after four hours of surgery,as well as postoperative complications,and recurrence rate between the two groups(P＞0.05).There was an signif-icant increase in sperm concentration,forward motile sperm rate,and normal sperm morphology rate in both of two groups after three months of surgery(P＜0.05).However,there was no significant difference between the two groups three months after surgery(P＞0.05).The surgical time and hospital stay were shorter than those of the control group(P＜0.05).And the treatment cost in observa-tion group was lower than that of the control group(P＜0.05).Conclusion:Both local anesthesia and lumbar anesthesia for MV treatment of VC have good efficacy and safety.However,patients treated with MV under local anesthesia for VC have obvious advanta-ges in terms of operation time(including anesthesia time),hospital stay,and treatment cost,which is worthy of clinical promotion and application.

This study analyzed the variations and evolution characteristics of influenza B Victoria(BV)virus in the Yellow River Delta region of China during 2021-2024.Throat swabs were collected from people with influenza-like illness(ILI)from 2021 to 2024 in Binzhou and Dongying,China.Viral isolation was performed,and 22 representative influenza BV isolates were selected for whole genome sequencing.Phylogenetic analysis of whole-genome sequences was performed in MegAlign and MEGA software.A total of 27 674 samples were obtained,and the overall positivity rate of influenza virus(A/H3N2,A/H1N1,BV)was 11.1％.Our surveillance data indicated that influenza B virus was detected in 2 years,which showed positivity rates of 28.2％and 1.7％,respectively.Statistically significant differences in the positivity rates of influenza BV viruses were observed(x2=3 641.791,P＜0.001).The median pairwise sequence identities ranged from 98.7％to 99.3％for eight segments of 22 viral sequences.The isolates for the monitoring years 2021-2024 were located in clades V1A.3a.1 and V1A.3a.2.Intra-lineage reassortments were discovered in B/shandongbincheng17/2022.The NA gene of one isolate exhibited an increase in the 488NLTV N-glycoproteome site.The K338R mutation occurred in the PA gene.Three locus deletion or insertion mutations occurred in the MP gene.The BV influenza epidemic was prevalent every other year;the intensity ranged from strong to weak;and the duration ranged from long to short in the Yellow River Delta region of China during 2021-2022.Influ-enza B virus formed intra-lineage reassortments,and showed significant mutations in NA gene,PA gene,and MP gene.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.