Objective: To investigate the effect of neurite outgrowth inhibitor extracellular peptide residues 1-40 (NEP1-40) combined with poly (lactic-co-glycolic acid) (PLGA) and gelatin electrospun fiber membrane on facial nerve repair in rats. Methods: According to the principle of random grouping, 108 male SD rats were divided into four groups (n = 27 in each group, approved by the ethics committee), namely, the sham group, control group, PLGA group, and NEP1-40 + PLGA group. A facial nerve fracture model was established for all of the groups except for the sham group. The control group received no further treatment, the PLGA group and the NEP1-40+PLGA group were supported by PLGA membrane, and the NEP1-40+PLGA group received one immediate local injection of NEP1-40 (5 μg/μL) at a dose of 10 μL. Facial nerve function analysis, electrophysiological examination, transmission electron microscope observation, HE staining, and immunohistochemical staining of myelin marker S100β and axonal marker β3-tubulin were used to evaluate the recovery of injured facial nerves of rats at 2, 4 and 8 weeks. Results : At 8 weeks, the facial nerve function score of the NEP1-40+PLGA group was better than that of the control group and PLGA group (P < 0.001), and facial nerve function was significantly restored. Electrophysiological examination of nerve action potentials at the injured facial nerve showed that the amplitude in the NEP1-40+PLGA group was higher than that of the control group and PLGA group (P < 0.001), but there was no significant difference in latency and conduction velocity results between the groups (P > 0.05). At 2, 4, and 8 weeks, transmission electron microscopy showed that the number of myelinated nerve fibers and myelin sheath thickness in the cross-section of the injured facial nerve in the NEP1-40+PLGA group were greater than those in the other groups (P < 0.05). At 8 weeks, HE staining showed that the facial nerves in the control group had partially recovered, but the overall cell distribution was uneven and the boundary with surrounding tissues was slightly blurred. In contrast, the NEP1-40+PLGA group had a relatively uniform cell distribution and a clearer boundary with surrounding tissues. At 2, 4, and 8 weeks, the immunohistochemical results showed that in the cross-section of the injuried facial nerve, NEP1-40 increased the expression of neural markers S100 β and β3-tubulin, especially β3-tubulin, which was close to normal levels (P > 0.05) Conclusion NEP1-40 is beneficial for the generation of new myelin sheaths and axons at the site of injury, and it can promote the repair and regeneration of injured facial nerves to a certain extent, thus accelerating the recovery of injured nerve function.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.

Objective To observe the value of nomogram model based on clinical and ultrasonic characteristics for diagnosing lymphoma.Methods Data of 176 patients with suspected lymphoma due to enlarged superficial lymph nodes were retrospective analyzed.The patients were divided into lymphoma group(n=90,invasive subgroup[n=40]and non-invasive subgroup[n=50])or non-lymphoma group(n=86)based on pathological results.Clinical and ultrasonic data were compared between groups and subgroups.Multivariate logistic regression was used to screen the independent risk factors of lymphoma,and then a nomogram was constructed.Receiver operating characteristic curves were drawn to evaluate the efficacy of conventional ultrasound,conventional contrast-enhanced ultrasound(C-CEUS),high-frame-rate contrast-enhanced ultrasound(H-CEUS)and nomogram for diagnosing lymphoma.Results Multivariate logistic regression analysis revealed that age＞59 years,cortical stripe/reticular hyperecho of lymph nodes and"centrifugal firework"enhancement pattern showed with H-CEUS were all independent risk factors of lymphoma(all P＜0.05).Taken 59 years as the best cut-off value of patients'age,the sensitivity,specificity,accuracy and the area under the curve(AUC)for diagnosing lymphoma was 67.78%,58.10%,63.06%and 0.630,respectively.The sensitivity,specificity,accuracy and AUC of cortical stripe/reticular hyperecho of lymph nodes for diagnosing lymphoma was 73.33%,58.10%,65.91%and 0.657,respectively,while of"centrifugal firework"pattern enhancement in H-CEUS was 77.78%,69.80%,73.86%and 0.738,respectively.AUC of conventional ultrasound,C-CEUS,H-CEUS and nomogram for diagnosing lymphoma was 0.657,0.540,0.738 and 0.844,respectively.Conclusion Nomogram model based on clinical and ultrasonic characteristics had good diagnostic efficacy for lymphoma,and"centrifugal firework"pattern enhancement in H-CEUS could be regarded as the specific characteristic of lymphoma.

Objective To explore the potential mechanism of action of paeoniflorin in diabetes mellitus,the related targets and pathways were preliminarily discussed,based on the network pharmacology and molecular docking technology.Methods Analyze the potential targets of paeoniflorin using the Swiss Target Prediction database.Genecards and OMIM databases yielded the genes of diabetes-related illnesses.After taking the intersection of the two,protein-protein interaction network(PPI)was established using STRING and Cytoscape programs to search for key genes with strong correlation and complete gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Use AutoDockTools and Pymol programs to complete protein molecule docking validation.Results The pharmacologically-related study revealed 63 targets associated with paeoniflorin,4 758 genes related to diabetes,and 50 intersection targets.15 key genes including vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),V-Ha-ras harvey(HRAS),V-src sarcoma(SRC)and heat shock protein hs 90-alpha(HSP90AA1)were screened.RAs-associated protein 1,Ras,calcium and other signaling pathways were obtained by KEGG pathway analysis.Molecular docking results showed that paeoniflorin had good binding ability with key genes.Conclusion Paeoniflorin can treat diabetes through multiple targets and pathways,and this mechanism can provide a basis for the application of paeoniflorin in anti diabetes and drug research and development.

Objective To explore the impact of knocking down Sec31A on the malignant phenotype of head and neck squamous cell carcinoma(HNSCC)and its possible mechanisms.Methods Transcriptome sequencing data of HNSCC tissues and adjacent tissues were obtained from the TCGA database,and the expression levels of Sec31A were compared.Immunohistochemical staining was used to analyze the expression of Sec31A in HNSCC tissues.Kaplan-Meier survival analysis was used to compare the relationship between Sec31A and the prognosis of HNSCC patients.Small interfering plasmids si-Sec31A and si-NC were transfected into HNSCC cell lines HN6 and HN4,and the impact of knocking down Sec31A on the biological behavior of HNSCC cells was detected through CCK-8 exper-iments,plate cloning experiments,scratch healing experiments,and Transwell experiments.Changes in the expression levels of PI3K/AKT/mTOR pathway related proteins in cells were detected after knocking down Sec31A with HN6 and HN4 through Western Blot(WB)experiments.Stable transfected cell lines of HN6 siSec31A and HN6 siNC were constructed and inoculated subcutaneously in nude mice to further verify the tumorigenic effect of Sec31A in vivo.Results TCGA data showed that Sec31A was higher in HNSCC tissues than in adjacent normal tissues(P＜0.01),and high expression of Sec31A was significantly correlated with poor prognosis in pa-tients(P＜0.05).Immunohistochemical staining showed that Sec31A was expressed stronger in HNSCC tissues than in normal tissues.In HN6 and HN4 cells,knocking down Sec31A resulted in significantly weaker proliferation,migration,and invasion abilities compared to the control group.Through WB experiments,it was found that transfection of si-Sec31A with HN6 and HN4 significantly reduced the expression levels of p-PI3K,p-AKT,and p-mTOR proteins.After knocking down Sec31A with HN6,the transplanted tumor volume in nude mice was significantly smaller than that in the control group.Conclusion Knocking down Sec31A can inhibit the proliferation,migration and invasion of HNSCC cells,possibly through the PI3K/AKT/mTOR pathway.

Objective To evaluate the intraoperative identification of ectopic parathyroid tissue in the central neck region using autofluorescence point-spectral analysis(AFPSA)combined with immune colloidal gold technique(ICGT),for guiding total parathyroidectomy(TPTX)or clean parathyroidectomy(CPTX)in the management of secondary hyperparathyroidism(SHPT).Methods Retrospectively collected and compared the clinical data of 64 patients with SHPT from October 2019 to June 2023.In the observation group,TPTX was performed as the initial procedure in 36 cases,followed by sampling of suspicious targets using AFPSA in the central neck area and subsequent detection through ICGT.CPTX was then conducted if a positive result was obtained.On the other hand,the control group consisted of 28 cases where only TPTX was performed without any additional tests during surgery.The surgical data,parathyroid hormone(PTH)levels,blood calcium levels,blood phosphorus levels,alkaline phosphatase(ALP)levels,regression of clinical symptoms,changes in parathyroid function and occurrence of hypocalcemia were compared between these two groups.Results In the observation group,there were 9 cases of AFPSA-ICGT positivity,including 2 left-sided cases,4 right-sided cases,and 3 thymic cases;among these posi-tive cases,there were a total of 10 locations with mildly hyperplastic or nonhyperplastic microscopic parathyroid tissue.The difference in the number of total parathyroid glands removed(including ectopic)between the two groups was statistically significant(P<0.05).At both 3 and 6 months postoperatively,ALP levels in the observation group were significantly lower than those in the control group(P<0.01 and P<0.001 respectively);at 6 months postoperatively,differences in PTH and blood phosphorus levels between the two groups were also statistically significant(P<0.05 and P<0.001 respectively).Joint bone pain and skin itching recurred in some patients within the control group at six months after surgery(P<0.05),whereas recurrence of SHPT was less frequent within the observation group compared to controls(P<0.05);however,no statistically significant differences were observed regarding postoperative hypoparathyroidism or hyperparathyroidism as well as hypocalcemia between either groups.Conclusion The AFPSA-ICGT intraoperative test can be utilized to guide surgery for SHPT,enabling accurate and efficient identification as well as safe targeting of parathyroid tissues that may not exhibit obvious hyperplasia in the central cervical region.

Objective To analyze the factors influencing the early recovery of renal function in patients with sepsis-associated acute kidney injury(SA-AKI).Methods A retrospective analysis was conducted on 86 SA-AKI patients treated in the Intensive Care Unit at Zhongshan Hospital,Fudan University from January 2021 to December 2022,who met both the Sepsis 3.0 diagnostic criteria and the AKI diagnostic standards.Patients were divided into a recovery group and a non-recovery group based on whether their renal function recovered within 7 days after AKI onset.Clinical data and laboratory tests of patients were compared between the two groups.Univariate and multivariate logistic analyses were used to identify risk factors affecting renal function recovery in SA-AKI patients,and ROC curve was utilized to evaluate the predictive value of these factors for early renal function recovery in SA-AKI patients.Results The renal function of 37(43.02％)patients recoveried.Compared with the recovery group,the renal replacement therapy rate,in-hospital mortality and 28-day mortality of patients in the non-recovery group were higher(P＜0.001).The multivariate logistic analysis showed that age,APACHE Ⅱ score,urine output,urine neutrophil gelatinase-associated lipocalin(NGAL),and norepinephrine dose were independent related factors affecting renal function recovery in SA-AKI patients(P＜0.05).The final model logit(P)=-4.091+0.001×urine NGAL-0.001 Xurine volume+0.040 ×age+0.073 × APACHE Ⅱ score+1.906 × norepinephrine dose.The AUC of model predicting early SA-AKI recovery was 0.823,with 73.5％of sensitivity,and 81.1％of specificity.Conclusions In SA-AKI patients,age,APACHE Ⅱ score,urine output,urine NGAL,and the dose of norepinephrine independently affect early renal function recovery,and the combined assessment of these indicators has predictive value for the early renal recovery in these patients.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objectives:To investigate the characteristics of clinical and imaging outcomes and their differ-ences between transforaminal endoscopic decompression and limited decompression and fusion surgery in the treatment of adult degenerative scoliosis(ADS).Methods:From January 2018 to January 2021,53 patients suf-fering from ADS who underwent surgery in our department were retrospectively analyzed,and they were divid-ed into either minimally invasive surgery(MIS)group(31 patients,underwent transforaminal endoscopic decom-pression)or fusion group(22 patients,underwent limited decompression and fusion surgery).The following data were comparatively analyzed:the baseline characteristics,the preoperative Lenke-Silva level,the radiographical parameters(scoliotic Cobb angle,global spinal balance parameters,and spinopelvic parameters)that measured at preoperation,before discharge,at six months after surgery,and at the final follow-up,clinical outcomes that evaluated at preoperation,before discharge,three months after surgery,six months after surgery,and the final follow-up,the incidence of surgical complications,and the reoperation rate.Results:The mean follow-up period was 15.68±3.26 months.The mean age of the patients in the MIS group was significantly higher than that in the fusion group(78.64±5.19 years vs 64.95±4.31 years,P＜0.05).In the MIS group,the majority of the patients were classified as Lenke-Silva Ⅰ and Ⅱ,and all the patients suffered from unilateral lower limb radiculopathy;In the fusion group,more patients were of Lenke-Silva Ⅱ and Ⅲ levels,and 73％of the patients suffered from unilateral lower limb radiculopathy.The preoperative scoliotic Cobb angle in the MIS group was significantly smaller than that in the fusion group(23.92°±9.06° vs 39.58°±13.12°,P＜0.05).Postop-eratively,both groups of patients showed significantly improvement in back pain,leg pain,and functional dis-ability.At the final follow-up,the scores for back pain and functional disability showed preferably improve-ment in the MIS group than those in the fusion group(P＜0.05).During the postoperative follow-up,no coronal or sagittal imbalance was observed in both groups;At the final follow-up:the mean scoliotic Cobb angle pro-gressed 1.51° in the MIS group,while the correction of scoliosis reduced 1.82° in the fusion group.The op-erative time,intraoperative blood loss,incidence of complications,and the reoperation rate in the MIS group were significantly lower than those in the fusion group(P＜0.05).Conclusions:For ADS patients without rigid imbalance,both surgical interventions are able to significantly improve clinical symptoms.The short-term fol-low-up outcomes reveal that the endoscopic decompression superiors in less scoliosis progression after opera-tion and functional improvement than limited fusion surgery.