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 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.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Objective To investigate the correlation of postoperative cytokine levels with infarct size and reperfusion injury in acute myocardial infarction(AMI)patients having achieved success-ful recanalization after PCI.Methods Clinical data of 164 AMI patients who underwent successful PCI in our department between March 2022 and March 2024 were collected and retrospectively analyzed.The levels of IL-6 and TNF-α were measured at 1 d after PCI,and base on the cutoff level,the patients were categorized into a high IL-6 group(≥5.72 ng/L,93 cases)and a low IL-6 group(＜5.72 ng/L,71 cases),and also into a high TNF-α group(≥5.27 ng/L,108 cases)and a low TNF-α group(＜5.27 ng/L,56 cases).General information,infarct volume and reperfusion injury were compared between the groups.Multivariate logistic regression analysis was used to identify the influencing factors of IL-6 and TNF-α.Pearson correlation analysis was employed to assess the correlation of IL-6/TNF-α levels with infarct size,while Spearman correlation analysis was utilized to evaluate their correlation with reperfusion injury.ROC curves were plotted to de-termine the predictive value of the two cytokines for reperfusion injury.Results The high IL-6 group showed significantly higher ratio of diabetes,larger proportion of reperfusion injury,greater infarct size,increased cardiac troponin I(cTnI)level,and longer PCI time than the low IL-6 group(P＜0.01),and similar results were seen in the high TNF-α group when compared with the low TNF-α group(P＜0.01).Multivariate logistic regression analysis identified PCI time(OR=3.492,95％CI:2.253-5.411),cTnI(OR=5.126,95％CI:1.104-23.787),infarct size(OR=1.178,95％CI:1.026-1.352),and reperfusion injury(OR=3.283,95％CI:1.099-9.809)as independent risk factors for elevated IL-6,while PCI time(OR=3.101,95％CI:2.027-4.742),cTnI(OR=3.498,95％CI:1.730-7.072),infarct size(OR=1.234,95％CI:1.051-1.449),and reperfusion injury(OR=3.518,95％CI:1.017-12.170)as independent risk factors for increased TNF-α.Pear-son and Spearman analysis showed that the IL-6 and TNF-α levels were positively correlated with infarct volume and reperfusion injury(P＜0.01).ROC curve analysis indicated that the AUC value of IL-6 and TNF-α in predicting reperfusion injury was 0.693(95％CI:0.616-0.762)and 0.681(95％CI:0.604-0.752),with a sensitivity of 60.49％and 81.25％,and a specificity of 71.08％and 78.81％,respectively.Conclusion In AMI patients after PCI recanalization,elevated IL-6 and TNF-α levels are positively correlated with infarct size and reperfusion injury,and the levels can serve as biomarkers for assessing the occurrence of reperfusion injury.

Malignant tumors(commonly referred to as cancer)represent a major global public health challenge and contribute significantly to the worldwide disease burden.Early screening plays a critical role in improving detection rates,enabling timely intervention,and enhancing pa-tient survival rates.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifical-ly rational,multi-cancer screening approach offers several advantages:it optimizes the use of bio-logical samples,reduces time costs for participants,enhances the efficiency and comprehensive-ness of screening,and minimizes overall expenses.Such an approach also facilitates the rational allocation of healthcare resources,ultimately helping to reduce the societal burden of cancer.To address this need,the Cancer Epidemiology Committee of the Chinese Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers in China.This consensus integrates multidisciplinary expertise and synthesizes the latest domestic and interna-tional researches on cancer screening,early detection,and treatment for prevalent malignancies.Drawing upon China's unique demographic and healthcare context,as well as practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the principles and methodologies established by the World Health Organization(WHO),aiming to:enhance the effectiveness of combined cancer screening in China,improve early detec-tion rates,and provide a scientific foundation for national cancer prevention and control strategies.

AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Malignant tumors(commonly referred to as cancers)represent a major global public health challenge and contribute substan-tially to the global disease burden.Early screening plays a crucial role in improving detection rates,enabling timely intervention,and enhan-cing patient survival.However,current cancer screening guidelines primarily focus on site-specific screening,which may not fully address the need for comprehensive early detection.A scientifically rational,multi-cancer screening approach offers several advantages:it optimizes the use of biological samples,reduces the time burden for participants,enhances the efficiency and comprehensiveness of screening,and min-imizes overall expenses.Moreover,this approach facilitates rational allocation of healthcare resources,ultimately helping to reduce the soci-etal burden of cancer.To address gap,the Cancer Epidemiology Committee of the China Anti-Cancer Association has developed the Expert Consensus on Combined Screening for Common Cancers.This consensus integrates multidisciplinary expertise and synthesizes the latest do-mestic and international researches on cancer screening,early detection,and treatment of prevalent malignancies.Drawing upon China's unique demographic and healthcare context and practical screening experiences,the consensus provides evidence-based recommendations on target populations,screening technologies,and procedural workflows for multi-cancer screening.These guidelines align with the prin-ciples and methodologies established by the World Health Organization(WHO),aiming to enhance the effectiveness of combined cancer screening in China,improve early detection rates,and provide a scientific foundation for national cancer prevention and control strategies.

Objective To preliminarily explore the safety of collecting colostrum in the third trimester,and to evaluate postpartum breastfeeding in pregnant women with hyperglycemia during pregnancy.Methods Pregnant women with hyperglycemia during pregnancy who had prenatal examinations in Obstetrics and Gynecology Hospital,Fudan University from Jul to Nov 2022 were prospectively divided into the colostrum collection group(n=52)in the third trimester and the control group(n=55)by randomized controlled grouping method.The t-test,χ2 test,Fisher's exact probability method and rank sum test were used for statistical analysis of the data to compare the delivery outcomes,neonatal outcomes and postpartum breastfeeding status between the two groups.Results There were no significant differences in the gestational weeks at delivery,delivery methods,breastfeeding rates at 42 days postpartum and 4 months postpartum between the two groups of pregnant women with hyperglycemia during pregnancy.There were also no significant differences in the Apgar scores at 1 minute and 5 minutes after birth and the neonatal hospitalization rate.The proportion of formula milk as the first supplementary feeding after delivery and the delayed lactation rate at 3 days postpartum in the colostrum collection group were significantly lower than those in the control group(P<0.05).The exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum in the colostrum collection group were significantly higher than those in the control group(P<0.05).Conclusion Collecting colostrum in the third trimester among pregnant women with hyperglycemia during pregnancy is safe,and it can reduce the rate of supplementary feeding with formula milk after delivery,and increase the exclusive breastfeeding rates at 24 hours postpartum and 3 days postpartum.

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.