Primary angiitis of the central nervous system （PACNS） is a rare immune-inflammatory disease confined to the small and medium blood vessels of the central nervous system， with unclear etiology and pathogenesis. The incidence of PACNS in the general population has not been accurately defined， and its clinical management is challenged by diagnostic difficulty， a high recurrence rate，and limited evidence supporting therapeutic interventions. The disease predominantly occurs in people aged 40‒60 years，with headache， cognitive impairment， and neurological deficits as the main clinical manifestations， which are non-specific.There are no characteristic indicators in laboratory tests， and cerebrospinal fluid examination can only rule out infection.Imaging findings include multiple infarctions and segmental vascular stenosis. Brain tissue biopsy is the gold standard for diagnosis. Clinically， the Calabrese and Mallek diagnostic criteria are often used， combined with supplementary criteria for stratified diagnosis. Treatment is based on glucocorticoids， with stratified induction， maintenance， and intensive therapy according to the type of involved blood vessels and disease severity， combined with immunosuppressants such as cyclophosphamide and mycophenolate mofetil. Biologics may be considered for refractory or recurrent cases.Long-term immunosuppressive therapy may reduce the risk of recurrence. Antiplatelet drugs， thrombolysis， and endovascular therapy can be used as needed. Currently， the diagnosis and treatment of PACNS still rely on diagnosis of exclusion and expert consensus，lacking high-level evidence.Future efforts should focus on exploring specific diagnostic markers and precise treatment regimens to promote standardized diagnosis and treatment.

ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

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.

Endoscopic full-thickness resection (EFTR) is a minimally invasive technique that is increasingly used for gastrointestinal stromal tumors (GISTs) originating from the muscularis propria. Despite its advantages over conventional surgery, such as complete tumor resection and faster recovery, EFTR faces challenges related to its efficacy, safety, and feasibility, particularly in gastric GISTs. By summarizing the literature published over the past decade, this review provides a comprehensive overview of the clinical outcomes of EFTR and the evolution of defect closure devices.

Hepatocellular carcinoma (HCC) imposes a major health and economic burden worldwide, with disproportionate effects in low- and middle-income countries (LMICs). Surveillance in high-risk populations, typically using semiannual ultrasound and alpha-fetoprotein testing, has been shown to be cost-effective by enabling earlier detection and improving survival. Yet, its overall value is reduced by poor adherence and the limited sensitivity of ultrasound, particularly in patients with metabolic-associated steatotic liver disease. Emerging approaches—including abbreviated magnetic resonance imaging, multi-biomarker models (e.g., gender, age, AFP, AFP-L3, and DCP), and liquid biopsy assays such as methylated DNA markers—demonstrate greater diagnostic accuracy and potential economic advantages compared with conventional methods. Integration of artificial intelligence into imaging may further enhance efficiency and reduce downstream costs. Moving toward precision surveillance, guided by individualized risk stratification that incorporates etiology, fibrosis stage, and molecular profiles, can optimize allocation of resources and maximize cost-effectiveness at the population level. Interventions to improve adherence, including mailed outreach and behavioral economic incentives, have shown both clinical benefit and cost savings, underscoring the role of implementation science. Because socioeconomic disparities influence both access and outcomes, economic models must explicitly address equity to achieve sustainable impact. Future research should prioritize prospective trials that evaluate not only clinical performance but also the real-world cost-effectiveness of novel technologies and stratified surveillance strategies. For LMICs, adapting proven models into affordable, context-appropriate programs is essential. By combining prevention, precision risk assessment, innovative technologies, and equitable implementation, HCC surveillance can deliver both clinical and economic value, reducing the global burden of disease.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

The efficient,precise,and rapid detection of trace copper ions(Cu2+)is of paramount importance in the realms of food safety,environmental monitoring,and medical health.By ingeniously utilizing the chemical properties of benzotriazole compounds in copper protection,and introducing an electrochemical reduction strategy,a silver nanoparticle composite structure supported by a nickel foam substrate was developed as an active platform for surface-enhanced Raman scattering(SERS)detection.This platform employed benzotriazole-5-carboxylic acid(BTAC)as a specific SERS probe molecule to achieve sensitive analysis of metal ion concentrations.The detection mechanism revealed a highly selective coordination between the Cu2+and the nitrogen atom in the triazole ring of BTAC,triggering subtle structural changes in the triazole ring.This was manifested by a significant and quantifiable shift in the characteristic peak of the SERS spectrum(particularly at 1001 cm-1),with a maximum shift of up to 30 cm-1.This phenomenon not only addressed the issue of reproducibility in quantitative analysis caused by the non-uniformity of SERS substrate materials but also significantly broadened the application boundaries of SERS technology for trace metal ion detection.It enabled ultra-sensitive detection of Cu2+concentrations ranging from 1×10-6 to 1×10-11 mol/L,with a detection limit as low as 1×10-11 mol/L,significantly enhancing detection sensitivity and accuracy.This work provided a novel and efficient strategy for rapid detection of trace Cu2+and enriched the application potential of SERS technology in food safety,environmental monitoring and biomedical analysis.

Objective To investigate the relationship between triple motif protein(TRIM)3,TRIM44 and clinicopathological parameters and prognosis in human papillomavirus(HPV)positive cervical cancer tissues.Methods The cancer tissues and adjacent normal cervical tissues(≥2 cm from the resection margin of the cancer)of 158 patients with HPV positive cervical cancer admitted to the hospital from February 2019 to Feb-ruary 2021 were selected,and the cancer tissues of 100 patients with HPV negative cervical cancer admitted to the hospital during the same period were selected.The positive expression rates of TRIM3 and TRIM44 in cancer tissues of HPV positive cervical cancer patients and their adjacent normal cervical tissues,and cancer tissues of HPV negative cervical cancer patients were detected and compared by immunohistochemistry.The relationship between the positive expression rate of TRIM3 and TRIM44 and the clinicopathological parame-ters of HPV positive cervical cancer patients was analyzed.The 3-year cumulative survival rate of patients with negative/positive TRIM3 expression and negative/positive TRIM44 expression were analyzed by Kaplan-Meier survival curve.The influencing factors of the prognosis of HPV positive cervical cancer patients were analyzed by COX regression model.Results Compared with adjacent normal cervical tissues and HPV nega-tive cervical cancer tissues,the positive expression rate of TRIM3 in HPV positive cervical cancer tissues was significantly decreased(P＜0.05),and the patients expression rate of TRIM44 was significantly increased(P＜0.05).Compared with the patients with FIGO stage Ⅰ A-Ⅰ B and no lymph node metastasis,the pa-tients with FIGO stage Ⅱ A and lymph node metastasis,the positive rate of TRIM3 expression decreased sig-nificantly(P＜0.05),while the positive rate of TRIM44 expression increased significantly(P＜0.05).A total of 3 patients were lost during the 3-year follow-up among 158 HPV positive cervical cancer patients,and 155 patients were finally followed up.Kplan-Meier survival curve showed that,the 3-year cumulative survival rate in TRIM3 negative expression group was significantly lower than that in TRIM3 positive expression group(P＜0.05).The 3-year cumulative survival rate in TRIM44 positive expression group was significantly lower than that in TRIM44 negative expression group(P＜0.05).COX regression analysis showed that lymph node metastasis,FIGO stage,negative expression of TRIM3 and positive expression of TRIM44 were risk factors for the prognosis of HPV positive cervical cancer patients(P＜0.05).Conclusion The expression of TRIM3 is low and the expression of TRIM44 is high in HPV positive cervical cancer tissues,which is relate to lymph node metastasis,FIGO stage and decrease 3-year cumulative survival rate.

The HACEK group microorganisms(Haemophilus parainfluenzae,Aggregatibacter actinomycetem-comitans,Cardiobacterium spp.,Eikenella corrodens,Kingella kingae)belong to Gram-negative bacilli and are members of the normal oropharyngeal microbiota,which can cause invasive opportunistic infection when the host immune barrier is damaged,with infective endocarditis being one of the most serious diseases.HACEK endocarditis is characterized by an insidious course,prolonged delay of diagnosis,and dependence on third-generation cephalo-sporins for treatment.In recent years,with the emergence and development of 16S ribosomal RNA gene sequencing technique,the rapid diagnosis of this disease is expected to be achieved.This paper summarizes the main clinical characteristics and research progress of infective endocarditis caused by HACEK group bacteria,aiming to provide reference for clinical diagnosis and treatment.