Objective:To discuss the effect of Yes-associated protein(YAP)silencing on the proliferation,migration,and invasion capabilities of the human cervical cancer(CC)SiHa cells.Methods:The human CC SiHa cells were cultured in vitro,and the lentiviral YAP shRNA was transfected into the SiHa cells to establish stably transfected YAP-shRNA experimental group(sh-YAP group)and empty plasmid control group(control group).Western blotting method was used to detect the silencing effect of YAP;immunofluorescence method was used to detect the microfilament number and morphology of actin filaments(F-actin)in the cells in both groups;CCK-8 method was used to detect the survival rates of the cells in two groups;Transwell chamber assay and wound healing assay were used to detect the numbers of migration and invasion cells and scratch healing rates of the cells in two groups;Western blotting method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)markers(E-cadherin and Snail),DNA damage repair-related proteins(γ-H2AX),and apoptosis-related proteins[c-MYC and B-cell lymphoma-2(Bcl-2)]in the cells in two groups.Results:The results of lentiviral YAP shRNA transfection into SiHa cells showed that the expression level of YAP protein in the SiHa cells was significantly decreased(P＜0.05).The immunofluorescence results showed that after YAP silencing,the F-actin in SiHa cells was sparse and regularly arranged,with a reduced number of cells and a shriveled appearance.The CCK-8 results showed that compared with control group,the survival rate of the SiHa cells in sh-YAP group was significantly decreased cultured for 24 and 48 h(P＜0.01).The results of Transwell chamber assay and the wound healing assay showed that compared with control group,the numbers of migration and invasion SiHa cells in sh-YAP group were significantly decreased(P＜0.01),and the cell scratch healing rates were signifiantly decreased(P＜0.05).The Western blotting results showed that compared with control group,the expression level of E-cadherin protein in the cells in sh-YAP group was increased(P＜0.05),and the expression levels of c-MYC,Bcl-2,and γ-H2AX proteins were decreased(P＜0.05 or P＜0.01).Conclusion:YAP gene silencing leads to the depolymerization of F-actin in the human CC SiHa cells and regulates the apoptosis and DNA damage repair,potentially reversing the EMT process,thereby inhibiting the proliferation and migration of the tumor cells.

Objective To investigate the effects of music therapy on cognitive function and immunity of sleep-deprived mice and the potential underlying mechanisms.Methods A novel music therapy was developed by integrating elements from both Western and Chinese music.A sleep-deprived mouse model was established to explore the effects of the music combination on learning and memory of mice using Morris water maze experiments.ELISA was used to detect immune-endocrine indicators in the blood and saliva of mice and to study the effects of this music combination on IgA levels.Transcriptome high-throughput sequencing and B-cell receptor(BCR)repertoire sequencing were adopted to explore the potential mechanisms through which music therapy influenced IgA production.Results The Morris water maze test revealed that the novel music therapy could promote the recovery of cognition and memory of sleep-deprived mice.Additionally,it was found that the music combination could increase IgA levels in both blood and saliva.Transcriptome high-throughput sequencing and BCR sequencing analysis showed that the music combination enhanced the abundance of the IgA immunoglobulin light chain variable region(Igkv4-53)and heavy chain constant region(Igha).Conclusion Music therapy can help restore cognitive function and increase IgA levels in sleep-deprived mice.The mechanism may be related to the enhanced abundance of immunoglobulin light chain variable region(Igkv4-53)and heavy chain constant region(Igha).

OBJECTIVE To provide reference for rational clinical use of mepolizumab. METHODS The reporting odds ratio method and Bayesian confidence propagation neural network method were used to conduct signal mining and analysis of adverse drug event （ADE） reports related to mepolizumab in the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2016 to the third quarter of 2022. RESULTS A total of 57 501 ADE reports were extracted with mepolizumab as the primary suspect drug， involving 16 358 patients. Among these reports， the proportion of males （23.51%） was lower than females （50.48%）. The reporting countries were primarily the United States （51.91%） and Canada （29.94%）. Consumers （71.18%） constituted the main reporting population. A total of 172 ADE-positive signals were identified， mainly involving 13 system organ classes such as the respiratory， thoracic and mediastinal disorders （41.63%）， as well as infectious and parasitic diseases （14.16%）. There were 60 high-risk signals， including 15 that were explicitly mentioned or related to adverse reactions in the drug instructions of mepolizumab and 45 signals （such as asthmatic crisis， sputum discoloured， purulent sputum， sleep disorder due to a general medical condition） were newly identified high-risk signals. Among them， 11 high-risk signals exhibited gender or age differences. CONCLUSIONS When clinically using mepolizumab， in addition to the adverse reactions mentioned in the drug instruction， special attention should also be given to changes in the nature of sputum， painful respiration， and sleep disorders.

Objective To analyze the clinical data of laparoscopic total hysterectomy after cervical cold knife conization (CKC) in patients with cervical intraepithelial neoplasia (CIN), and study the supplemental treatment methods after cervical cold knife conization in patients with CIN Ⅲ. Methods The clinical data of 101 patients with CIN Ⅲ were retrospectively analyzed, the patients were treatment with laparoscopic total hysterectomy after cervical cold knife conization. Results Among the 101 patients, the accordant pathological result of cervical biopsy under colposcopy and cervical cold knife conization was in 68 cases (67.3%), while 6 cases (5.9%) pathological upgraded to invasive carcinoma. The positive margins after cervical cold knife conization was in 23 cases, and negative margins was in 78 cases. Among the positive margins patients, 11 cases had residual lesion, including 2 cases of CINⅠ, 2 cases of CINⅡ, 5 cases of CIN Ⅲ, 2 cases of microinvasive carcinoma. The rate of residual lesions was 47.8%(11/23). Among the negative margins patients, 7 cases had residual lesion, including 4 cases of CINⅠ, 2 cases of CIN Ⅱ, 1 case of CIN Ⅲ. The rate of residual lesions was 9.0% (7/78). There was statistical difference in the rate of residual lesions between 2 groups (P<0.05). Conclusions The cervical biopsy under colposcopy has high risk of missing diagnosis of cervical cancer, thus it can not replace the diagnosis of cervical cold knife conization. There is still a certain percentage of residual lesions in the negative margins of cervical cold knife conization. The patients with recurrence or residual risk factors may be considered further surgical treatment.

[ ABSTRACT] AIM:To investigate the effects of Chaihu Shugan powder ( CSP) on lipid metabolism and the pro-teins involved in adenosine 5’-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver tissues of the rats with non-alcoholic fatty liver disease (NAFLD).METHODS: Sprague-Dawley rats were randomly di-vided into normal control ( NC) group, with HFD ( HFD) group and CSP group.The NAFLD models were established by feeding with HFD for 16 weeks in the rats.The rats in CSP group were intragastrically administered with CSP extracts (9.6 g· kg-1 · d-1 ) , and blood and liver samples were collected 16 weeks later.Serum and liver levels of total cholesterol ( TC) and triglyceride ( TG) , and serum levels of alanine aminotransferase ( ALT) and aspartate aminotransferase ( AST) were measured using an automatic biochemical analyzer.The histological changes of liver tissues were observed with HE staining, while the lipid deposition was observed with Oil Red O staining.The ultrastructural changes of the liver tissues were observed under transmission electron microscope.Moreover, the protein levels of AMPK, phosphorylated AMPK (pAMPK), SIRT1 and uncoupling protein 2 (UCP2) in the liver were detected by Western blot.RESULTS:The results of HE staining, Oil Red O staining and electron microscopy demonstrated that NAFLD rat model was successfully estab-lished.Compared with NC group, the serum and liver levels of TC and TG, and serum level of AST in model group were markedly elevated ( P<0.01) .Moreover, the protein levels of pAMPK and SIRT1 in HFD group were markedly reduced (P<0.01), whereas UCP2 level was elevated (P<0.01).Furthermore, liver levels of TC and TG, and serum level of AST in GSP group were markedly reduced as compared with HFD group ( P<0.05 ) .The protein levels of pAMPK and SIRT1 were elevated ( P<0.05 ) , whereas the UCP2 level was reduced as compared with HFD group ( P<0.01 ) .The protein level of AMPK between the 3 groups had no significant difference.CONCLUSION: CSP attenuates hepatic lipid disorder and hepatic lipid deposition in NAFLD rats induced by feeding with HFD for 16 weeks, which is associated with the activation of AMPK/SIRT1 pathway.