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.

ObjectiveTo explore the mechanism by which Zuoguiwan improves the pancreas development in the gestational diabetes mellitus （GDM） model by observing the effects of Zuoguiwan on the expression of key regulatory factors in different stages of pancreas development. MethodsPregnant Wistar rats were randomly assigned into blank， model， insulin detemir （20 U·kg^-1） and Zuoguiwan （1.89 g·kg^-1） groups （n=18）. GDM was induced by peritoneal injection of streptozotocin on day 6.5 （E6.5d） in the embryonic stage， and the blank group was given an equal volume of sodium citrate buffer. The modeling performance was assessed by measuring the blood glucose of pregnant rats. Except the blank group and model group， pregnant rats in other groups were administrated with corresponding drugs from E9.5d to delivery. The random blood glucose of pregnant rats was monitored， and the embryos and offspring rats were measured for the length and weighed on E12.5d， E18.5d and day 21 after birth （B21d）. The Lee's index of rats on B21d was calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the fasting insulin （FINS） levels of B22d rats and the Homeostasis Model Assessment for Insulin Resistance （HOMA-IR） was calculated. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total bilirubin （TBIL）， total cholesterol （CHO）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL） in E18.5d pregnant rats and B22d offspring were determined. The pathological changes in the pancreas of E12.5d， E18.5d and B22d rats were observed by hematoxylin-eosin （HE） staining. Western blot was used to determine the protein levels of pancreatic duodenal homeobox 1 （Pdx1）， pancreas-specific transcription factor 1a （Ptf1a）， and sex-determining region Y-box protein 9 （Sox9） in the pancreas of E12.5d embryos， Pdx1， Nkx2 homeobox 2 （Nkx2.2）， and hairy and enhancer of split-1 （Hes1） in the pancreas of E18.5d embryos， and Pdx1， v-maf musculoaponeurotic fibrosarcoma oncogene homolog A （Mafa）， and NK transcription factor-related homeobox gene family 6 locus 1 （Nkx6.1） in the pancreas of B22d rats. ResultsCompared with the blank group， the model group showed elevated blood glucose levels in pregnant rats on B0d， E9.5d， E12.5d， E15.5d， and E18.5d （P<0.05， P<0.01）， decreased body weight and body length （P<0.01） and increased Lee's index in the offspring. In addition， the B22d offspring showed rising levels of FBG， FINS， HOMA-IR， AST， and TG （P<0.01）， a declined level of HDL （P<0.01）， and pancreatic acinous cells with edema and loose arrangement. The pregnant rats on E18.5d exhibited raised levels of ALT， AST， and TG （P<0.05， P<0.01） in the pancreas and a declined level of HDL （P<0.05）. The E12.5d embryos showed up-regulated protein levels of Pdx1， Sox9， and Ptf1a in the pancreas （P<0.01） and the E18.5d embryos exhibited down-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas （P<0.01）. The protein levels of Pdx1， Nkx6.1， and Mafa in the pancreas of B22d offspring were down-regulated （P<0.01）. Compared with the model group， the insulin group exhibited lowered blood glucose in pregnant rats on B0d， E15.5d， and E18.5d （P<0.05， P<0.01）. The offspring in all treatment groups showcased increased body weight and body length （P<0.01） and decreased Lee's index. The B22d offspring exhibited declined levels of FBG， FINS， and HOMA-IR in the insulin group （P<0.01） and lowered levels of FBG and HOMA-IR in the Zuoguiwan group （P<0.01）. The B22d offspring in all the treatment groups showed reduced levels of ALT， AST， TBIL， CHO， TG， and LDL， a raised level of HDL， and alleviated edema of pancreatic acinous cells. The pregnant rats on E18.5d demonstrated declined levels of TG and ALT （P<0.05， P<0.01） and an elevated level of HDL （P<0.05）. The pancreas of E12.5d embryos presented down-regulated protein levels of Pdx1 and Sox9 and an up-regulated protein level of Ptf1a in the insulin group （P<0.05）. The pancreas of E12.5d embryos in the Zuoguiwan group presented down-regulated protein levels of Pdx1， Sox9， and Ptf1a （P<0.01）. All the treatment groups showed up-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas of E18.5d embryos （P<0.01） and Pdx1， Nkx6.1， and Mafa in the pancreas of B22d embryos （P<0.05， P<0.01）. ConclusionZuoguiwan can promote the growth and development and ameliorate the pathological changes in the pancreas of the offspring of GDM model by regulating the expression of Pdx1 pathway-related regulatory factors in different stages of pancreas development.

Objective:To investigate the response of mandibular condylar chondroprogenitors to flow fluid shear stress(FFSS).Methods:Chondroprogenitors were in vitro cultured and stimulated with FFSS that can cause cell degeneration,and treated with sec-ond-generation high-throughput RNA sequencing.Differential gene expression was screened using DESeq2 software for gene ontology(GO)functional enrichment analysis,kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and protein-protein interaction(PPI)network analysis.qRT-PCR was performed to validate the core genes screened by PPI.Results:A total of 1996 differentially expressed genes were obtained,mainly including inflammatory response and cell cycle related molecules.Among them,Actal,Atf3,Ccl2,116,Nfkbia,Ret and Vcaml were identified as the core genes.Conclusion:FFSS stimulation affects chondroprogenitor function by acting on inflammatory responses and cell cycle-related signaling pathways in chondroprogenitors.

Objective:To investigate the effects of the taurochenodeoxycholic acid(TCDCA)on cartilage degeneration in tem-poromandibular joint osteoarthritis(TMJ OA).Methods:36 female SD rats aged 6 weeks were randomly divided into 3 groups:con-trol group(CON),unilateral anterior crossbite group(UAC),UAC plus TCDCA injection group(UAC+TCDCA).UAC model was es-tablished in all rats in UAC and UAC+TCDCA groups.Samples were collected at 8 and 12 weeks(control group,UAC group,UAC+TCDCA group)after set up of the experiment(n=6),and TMJ morphological examination was performed.The expression of CYP7A1,BAAT and TGR5 in the tissue and cells was examined by immunohistochimical staining.Results:(1)Compared with the CON group of the same age,the cells in the condylar cartilage were disordered,the cartilage matrix was reduced and thinner in UAC group.Compared with UAC group of the same age,cell arrangement,cell number,cartilage matrix and cartilage thickness were im-proved in UAC+TCDCA group(P＜0.05).(2)Compared with the CON group of the same age,the positive cells for TCDCA-specific receptor TGR5 and the key enzymes CYP7A1 and BAAT were mainly distributed in the anterior hypertrophic layer and hypertrophic layer at each time point.The number of positive cells in the UAC group was significantly reduced compared with the CON group.Conclusion:TCDCA has obvious therapeutic effects on the degeneration in TMJ OA.

Objective To investigate the genetic characteristics and recombination of human-infected sapoviruses(SaVs)worldwide using bioinformatics.Methods The complete genome sequences of SaVs were downloaded from the National Center for Biotechnology Information(NCBI)while high-quality complete genomes were retained for analysis.Molecular phylogenetic trees of SaVs were constructed to analyze their genetic characteristics,followed by recombination analysis of human-infected SaV strains genetype Ⅰ,Ⅱ,Ⅳ,and V(G Ⅰ,G Ⅱ,GⅣ,and GⅤ)with recombination analysis software.Results SaVs exhibited substantial genetic diversity worldwide and infected a wide range of hosts.Human-associated SaVs included G Ⅰ,G Ⅱ,GⅣ,and GⅤ,with GⅤ shared between human and swine hosts.Genetype recombination analysis of SaVs revealed a high frequency of recombination in SaV G Ⅱ strains that involved diverse hosts in the field of SaV G V strains.Recombination breakpoints of the virus were concentrated in the major viral proteins 1(VP1)and minor viral proteins 2(VP2).Conclusion Based on systematic analysis of the genetic characteristics of human-infected SaVs,the genotype distribution and prevalence of SaVs are investigated,the recombination patterns of SaV revealed,and its genetic dynamics highlighted.These findings can offer insights into epidemiological trends of viruses and help devise effective prevention and control strategies.

Objective : To investigate the impact of SOX4 on ovarian granulosa cells，stable overexpression of SOX4 was achieved in human KGN cell line，followed by analysis of its effects on proliferation，migration and apoptosis. Methods : The recombinant lentiviral plasmid pLV-EF1a-GFP / Puro-SOX4 was generated through homologous recombination with linearized pLV-EF1a-GFP / Puro vector．Human ovarian granulosa cells ( KGN cell line ) were transduced with Lentiviral expression vectors．KGN cells infected with pLV-EF1a-GFP / Puro-NC were served as the LV-CON group，while those infected with pLV-EF1a-GFP / Puro-SOX4 were designated as the LV-SOX4 group．Following transfection，puromycin selection was employed to establish stable SOX4-expressing KGN cells．The expres- sion levels of SOX4 m RNA and protein in KGN cells from the LV-CON and LV-SOX4 groups were assessed using RT-qPCR and Western blot analysis．Cell proliferation was assessed using the CCK-8 assay in both LV-CON and LV-SOX4 groups．Cell migration ability was evaluated by means of a cell scratch test in these two groups．The proportion of apoptotic cells was determined via flow cytometry analysis in both LV-CON and LV-SOX4 groups. Results: The sequencing results of pLV-EF1a-GFP / Puro-SOX4 indicated a complete match between the inserted gene se- quence and the SOX4 mRNA sequence．The lentiviral titers were 7 × 108 TU / ml in the LV-CON group and 1 × 108 TU / ml in the LV-SOX4 group．The recombinant plasmid was successfully transfected into KGN cells with a transfection efficiency of over 90% under fluorescence inverted microscopy．The results of RT-qPCR and Western blot tests demonstrated a significant increase in the expression level of SOX4 in KGN cells of LV-SOX4 group compared to that of LV-CON group (t = 3. 10，P ＜0. 05 ; t = 14. 20，P ＜0. 05) ．The CCK-8 assay results demonstrated that the LV-SOX4 group exhibited a significant increase in cell proliferation (24 h : t = 45. 92，P＜0. 01 ; 72 h : t = 25. 60，P ＜0. 01) compared to the LV-CON group．The cell scratch assay indicated that the migratory capacity of KGN cells in the LV-SOX4 group was significantly enhanced (t = 7. 65，P ＜0. 01) compared to that in the LV-CON group. The LV-SOX4 group exhibited a significant reduction in apoptosis ratio (t = 25. 84，P＜0. 01) compared to the LV- CON group． Conclusion SOX4-overexpressing KGN cell line was successfully established，and the overexpression of SOX4 facilitated proliferation and migration while inhibiting apoptosis in human ovarian granulosa cells.

Objective:To explore the research hotspots of early enteral nutrition and analyze its development trend.Methods:The Web of Science core database was retrieved. HistCite and CiteSpace were used to conduct quantitative analysis and co-word clustering analysis of early enteral nutrition.Results:A total of 823 articles were retrieved, and the number of articles was increasing. The research hotspots of early enteral nutrition mainly included severe disease, esophageal cancer, acute pancreatitis, sepsis, malnourished patients and premature infants. At the same time, the selection of early enteral nutrition nutrients was also a research hotspot.Conclusions:Early enteral nutrition research in critically ill patients is mature, and other specialized fields can carry out specialized early enteral nutrition support based on the research on critically ill patients. In the future, comparative studies on the effects of different nutrients in early enteral nutrition can also be carried out.

Peripheral nerve injury (PNI) is a common disease in the oral cavity that can easily lead to loss of function and abnormal appearance. The application of dental pulp stem cells (DPSCs) combined with tissue engineering in the repair of PNI is a research hotspot. DPSCs have the advantages of abundant sources, simple extraction, low immunogenicity and a high proliferation rate in vitro. They can differentiate into Schwann cells (SCs). SCs can induce autophagy and secrete key neurotrophic factors, such as nerve growth factor, brain-derived neurotrophic factor, ciliary neurotrophic factor and glial cell-derived neurotrophic factor. SCs are beneficial for the repair of nerve injury. DPSCs in different periods have differences in immune regulation, anti-inflammatory effects, expression of neural markers, angiogenesis and so on, which provide more diversified choices for nerve repair. At present, the introduction of tissue engineering provides a more controllable and improved microenvironment for DPSCs, which is conducive to the application and development of DPSCs in regenerative medicine and tissue engineering. However, there are still many problems to be solved, such as the selection of stem cells, functional link recovery, uncontrollable direction of axon regeneration, regulation of the peripheral nervous system and mechanism of repair.

Oral squamous cell carcinoma (OSCC) is a common cancer that develops from oral epithelial cells, it has a high incidence, mortality and teratogenic rate, which poses a serious threat to people′s life and health.The Hippo signaling pathway plays a key role in tumorigenesis, regulation of stem cell homeostasis, tissue regeneration, and organ size control. In OSCC, activation of Hippo signaling pathway can inhibit malignant biological behavior, epithelial mesenchymal transformation and distant metastasis of tumors, and improve the survival rate of patients. Considering the importance of the Hippo signaling pathway in the development of cancer, this paper summarized the composition and regulatory mechanism of Hippo pathway, elaborated the role of Hippo signaling pathway in the occurrence and development of OSCC.At the same time, make a simple generalization about the potential therapeutic approaches and strategies to reduce the risk of drug resistance for OSCC patients targeting this pathway.

To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.