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.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

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.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

ObjectiveTo understand the infection characteristics and drug resistance of carbapenem-resistant Serratia marcescens (CRSM) in a general hospital in Shanghai, and to provide a theoretical basis for clinical anti-infective treatment and prevention of drug-resistant bacteria. MethodsClinical data on cases with CRSM infections detected in clinical specimens at a gradeⅢ level A general hospital in Shanghai from June 2022 to June 2024 were retrospectively collected, and their clinical distributions, factors of hospital-acquired infections, prognosis, and drug-resistant situation were analyzed simultaneously. ResultsA total of 38 cases with CRSM were detected from June 2022 to June 2024, and the number of CRSM strains accounted for 25.00% (38/152) of the number of SM strains. The 38 CRSM infection samples were all derived from sputum. CRSM were distributed in 9 clinical departments, and the top 3 departments having the highest percentages of CRSM among SM strains, were intensive care unit (ICU) (78.79%, 26/33), gastrointestinal surgery department (57.14%, 4/7), and thyroid hernia surgery department (50.00%, 1/2). Among the 38 patients with CRSM infections, 8 cases were identified as hospital-acquired infection, resulting in a hospital-acquired infection rate of 21.05. The mortality rate of the 38 cases of CRSM infected patients within 30 days after detection of CRSM was 23.68% (9/38). The results of multivariate logistic regression analysis showed that sequential organ failure assessment (SOFA) score ≥6.5 points (OR=15.33, P<0.001), septic shock (OR=4.85, P=0.032), and suffering from neoplastic diseases (OR=0.12, P=0.018) were the related factors for death within 30 days after the detection of CRSM in patients with CRSM infection. The results of drug sensitivity test showed that the 38 cases of CRSM exhibited 100.00% (38/38) sensitivity to trimethoprim/sulfamethoxazole, tigecycline, or ceftazidime/avibactam; demonstrated high resistance toβ-lactams except for ceftazidime (18.42%, 7/38), the latter of which was one of the third-generation of cephalosporins; showed elevated resistance to fluoroquinolones [levofloxacin (89.47%, 35/38), ciprofloxacin (94.74%, 36/38)]; maintained good tetracycline sensitivity [doxycycline (97.37%, 37/38), minocycline (76.32%, 29/38)]; and displayed high susceptibility to the aminoglycoside gentamicin (94.74%, 36/38) and elevated resistance to tobramycin (86.84%, 34/38). The detection rate of serine carbapenemase in the 38 strains of CRSM was 100.00%, while all strains tested negative for metallo-β-lactamases. ConclusionFrom June 2022 to June 2024, the detection rate of CRSM in a gradeⅢ level A general hospital in Shanghai was relatively high, especially in the ICU. CRSM has a high resistance rate to commonly used antibacterial drugs such as the first and second-generation cephalosporins, quinolones, and polypeptide antibacterial drugs. Therefore the dynamics of drug-resistant bacteria should be tracked in a timely manner to guide the rational clinical application of antibacterial drugs.

OBJECTIVE To systematically evaluate the efficacy and safety of different chemotherapy combination regimens for first-line treatment of metastatic colorectal cancer （mCRC）. METHODS PubMed， Cochrane Library， Embase and Web of Science were electronically searched to collect randomized controlled clinical trial （RCT） on first-line treatment for mCRC from January 1， 2000 to February 16， 2025. Two reviewers independently screened literature， extracted data and assessed the risk of bias of the included studies. Network meta-analysis was performed by using R4.4.3 and Stata 17.0 software. RESULTS A total of 28 RCTs， involving 16 intervention measures， were included. In terms of prolonging progression-free survival （PFS） and overall survival （OS）， FOLFOX （5-fluorouracil+oxaliplatin+calcium folinate regimen）+cetuximab had the highest probability of ranking first. In terms of improving objective response rate （ORR）， FOLFOXIRI （5-fluorouracil+oxaliplatin+irinotecan+calcium folinate regimen）+ bevacizumab and FOLFOX+bevacizumab+nivolumab had the highest probability of ranking first； in terms of the incidence of grade 3 or higher adverse reactions， FOLFOXIRI+panitumumab had the highest probability of ranking first； in subgroup analysis of KRAS wild-type patients， FOLFIRI （5-fluorouracil+irinotecan+calcium folinate regimen）+panitumumab and FOLFIRI+bevacizumab had the highest probability of ranking first in terms of prolonging PFS and OS， respectively； in terms of ORR， FOLFOXIRI+ cetuximab had the highest probability of ranking first. CONCLUSIONS In first-line treatment for mCRC， FOLFOX combined with targeted therapy has advantages in terms of efficacy and safety. However， individualized treatment strategies should be formulated based on the KRAS gene status and tumor location of patients.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.