Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Objective To explore the value of clinical-MRI radiomics combined model for differentiating borderline ovarian tumor(BOT)from epithelial ovarian cancer(EOC).Methods Totally 139 patients with BOT(BOT group)and 307 patients with EOC(EOC group)confirmed by postoperative pathology and underwent preoperative pelvic MRI were retrospectively enrolled and randomly divided into training set(n=312)and test set(n=134)at a ratio of 7∶3.Multivariable logistic regression was used to identify independent clinical predictors for differentiating BOT and EOC,then a clinical model was constructed.Radiomics features were extracted from the volumes of interest(VOI)of lesions on T2WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images,respectively,and single-sequence and multi-sequence MRI radiomics models were built using extreme gradient boosting(XGBoost)based on data in training set.The optimal MRI radiomics model was selected according to the highest area under the curve(AUC)in test set,and a clinical-MRI radiomics combined model was constructed combined the optimal radiomics model with independent clinical predictors.The performances of clinical model,the optimal MRI radiomics model and the combined model for differentiating BOT and EOC were compared in test set.SHapley Additive exPlanations(SHAP)analysis was applied to interpret key predictive features in the best model.Results Patients' age,carbohydrate antigen 153(CA153)and carbohydrate antigen 125(CA125)were all independent predictors for differentiating BOT and EOC(all P＜0.05).Multi-sequence MRI radiomics model was the optimal MRI radiomics model.The combined model showed superior performance(AUC=0.929)for discriminating BOT and EOC compared with clinical model(AUC=0.881)and multi-sequence MRI radiomics model(AUC=0.871)(both P＜0.05).SHAP beeswarm plot revealed that the top 10 important features of combined model included age,CA153 and CA125,as well as entropy,kurtosis and gray level non-uniformity from ADC and DWI sequences.Conclusion Clinical-MRI radiomics combined model based on multi-sequence MRI radiomics features and clinical features could be used to effectively differentiate BOT from EOC.

Objective:To construct a VP8-mRNA vaccine using human rotavirus spike protein VP8 domain as the immunogen and analyze its immunogenicity in mice.Methods:The VP8-mRNA sequence was designed, optimized, and synthesized. The VP8 gene of rotavirus G1P[8] type was used to construct the plasmid pUC57-VP8-Kan-SapⅠ, which was then sequenced. The plasmid confirmed by sequencing was subjected to large-scale amplification and extraction, followed by linearization, in vitro transcription, and capping. The purified capped products were encapsulated with lipid nanoparticles using a microfluidic control apparatus. The encapsulated VP8-mRNA vaccine was administered intramuscularly to mice at 10, 15, and 20 μg. Serum samples were collected for antibody detection by ELISA. Cellular immune responses were detected by flow cytometry and ELISPOT. Statistical analysis was performed using one-way or two-way analysis of variance and Tukey-Kramer test. Results:The encapsulated VP8-mRNA vaccine was rounded and spherical, with a particle size of about 100 nm, a polymer dispersion index of 0.088, and an encapsulation rate of 92.3%. Two doses of VP8-mRNA vaccine immunization could induce a good immune response in mice. The level of IgG antibody induced after immunization in the 15 μg group was comparable to that of the 20 μg group, and there was no statistical difference ( P>0.05), but the antibody levels in the two groups were significantly higher than that in the 10 μg group ( P<0.000 1). VP8-mRNA vaccine could induce neutralizing antibodies against rotavirus G1 and G9 types. The highest level of neutralizing antibodies against rotavirus type G1 was observed in the 15 μg group, which was significantly higher than that in the 10 μg group ( P<0.05). All immunization groups exhibited good neutralizing ability against rotavirus G9 type. The results of ELISPOT showed that lymphocytes from mice in each vaccine group were able to secrete IFN-γ when stimulated with VP8 peptide. Flow cytometry showed that the proportions of CD8 + T cell subsets in the vaccine groups were higher than that in the control group. Conclusion:The VP8-mRNA vaccine has good immunogenicity in mice and can induce good humoral and T-cell immune responses.

A throat swab sample from a pediatric case in Tongzhou District, Beijing was identified as enterovirus; the patient was a 1-year-and-8-month-old male sporadic case. Whole-genome sequencing revealed a viral genome length of 7 436 bp. BLAST alignment confirmed the serotype as EV-D68. Phylogenetic analysis of the whole genome indicated that this strain belongs to the B3 clade, showing closer genetic proximity to the 2018 Shanghai strain MW697453 with 99.53% whole-genome nucleotide homology. Genetic and amino acid variation analysis demonstrated that the B3 subclade to which this strain belongs exhibits a nucleotide deletion at positions 718–726, differing from deletion sites observed in other B3 clade strains. A key neuropathogenic amino acid site, T650A, was found to have undergone mutation. Recombination analysis confirmed no cross-clade recombination events in this strain. This study conducted genetic characterization of the strain's evolutionary relationship with EV-D68 strains from different regions and years in China, providing data support for formulating prevention and control measures against EV-D68 infection.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To investigate the correlation between insulin resistance markers[triglyceride-glucose(TyG)index],inflammatory indicators[neutrophil-to-lymphocyte ratio(NLR),C-reactive protein(CRP)],and traditional Chinese medicine(TCM)syndromes in patients with diabetic kidney disease(DKD)complicated by carotid atherosclerosis(CAS).Methods This retrospective study enrolled 300 DKD patients with CAS(case group)and 30 DKD patients without CAS(control group).Differences in TyG index,NLR,and CRP levels were compared between groups.The relationships between these markers and carotid intima-media thickness(IMT)/plaque area were analyzed,along with their variations across TCM syndromes.Logistic regression and receiver operating characteristic(ROC)curve analyses were performed to evaluate the predictive value of TyG index,NLR,and CRP for plaque stability and prognosis.Results(1)The TyG index,NLR,and CRP levels in patients with DKD and CAS were significantly higher than those in patients with DKD alone(P＜0.01).(2)The TyG index,NLR,and CRP were significantly positively correlated with IMT and plaque area(P＜0.01).(3)In patients with DKD combined with CAS,the TyG index,NLR,and CRP levels in those with unstable plaques were significantly higher than those with stable plaques(P＜0.01).(4)Among the distribution of TCM syndromes in patients with DKD combined with CAS,the qi and yin deficiency syndrome had the highest proportion(33.33％),followed by spleen and kidney yang deficiency syndrome(28.67％),yin and yang deficiency syndrome(22.00％),and turbid toxin and stasis obstruction syndrome(16.00％).(5)Among patients with DKD and CAS,the TyG index,NLR,and CRP levels in patients with different TCM syndromes decreased in the following order:turbid toxin and stasis obstruction syndrome,yin and yang deficiency syndrome,spleen-kidney yang deficiency syndrome,and qi and yin deficiency syndrome.(6)Logistic regression analysis results showed that TyG index,NLR,and CRP levels were closely associated with plaque stability in patients with DKD combined with CAS(P＜0.05 or P＜0.01).(7)ROC analysis showed that these markers have high prognostic value in DKD-CAS(P＜0.01).Conclusion TyG index,NLR,and CRP may serve as potential biomarkers for TCM syndrome differentiation and prognosis assessment in DKD-CAS.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4％(21/52),pCR 42.9％(9/21).The other 31 cases have complete response 5.8％(3/52),PR 25.0％(13/52),PD 11.5％(6/52),SD 17.3％(9/52).The overall objective response rate(ORR)was71.2％(37/52),and the disease control rate(DCR)was 88.5％(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.