OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

ObjectiveHuman Ku70 protein mainly involves the non-homologous end joining (NHEJ) repair of double-stranded DNA breaks (DSB) through its DNA-binding properties, and it is recently reported having an RNA-binding ability. This paper is to explore whether Ku70 has RNA helicase activity and affects miRNA maturation. MethodsRNAs bound to Ku protein were analyzed by RNA immunoprecipitation sequencing (RIP-seq) and bioinfomatic anaylsis. The expression relationship between Ku protein and miRNAs was verified by Western blot (WB) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays. Binding ability of Ku protein to the RNAs was tested by biolayer interferometry (BLI) assay. RNA helicase activity of Ku protein was identified with EMSA assay. The effect of Ku70 regulated miR-124 on neuronal differentiation was performed by morphology analysis, WB and immunofluorescence assays with or without Zika virus (ZIKV) infection. ResultsWe revealed that the Ku70 protein had RNA helicase activity and affected miRNA maturation. Deficiency of Ku70 led to the up-regulation of a large number of mature miRNAs, especially neuronal specific miRNAs like miR-124. The knockdown of Ku70 promoted neuronal differentiation in human neural progenitor cells (hNPCs) and SH-SY5Y cells by boosting miR-124 maturation. Importantly, ZIKV infection reduced the expression of Ku70 whereas increased expression of miR-124 in hNPCs, and led to morphologically neuronal differentiation. ConclusionOur study revealed a novel function of Ku70 as an RNA helicase and regulating miRNA maturation. The reduced expression of Ku70 with ZIKV infection increased the expression of miR-124 and led to the premature differentiation of embryonic neural progenitor cells, which might be one of the causes of microcephaly.

Objective To observe the effect of parecoxib sodium combined with dexmedetomidine preemptive analgesia on postoperative analgesia in patients with modified radical mastectomy for breast cancer.Methods Patients who underwent modified radical mastectomy for breast cancer were randomly divided into control group and treatment group based on simple binary randomization by random number table method.In the control group,"0.05 mg·kg-1 midazolam+1.0-1.5 mg·kg-1 propofol+0.4 μg·kg-1sufentanil citrate+0.15 mg·kg-1 phenylsulfonyl cisatracurium"was used for induction and maintenance of anesthesia.In the treatment group,the induction and maintenance of anesthesia was performed with the protocol of"parecoxib sodium 40 mg+dexmedetomidine 0.5 μg·kg-1·h-1)continuous pumping"on the basis of control group,and mechanical ventilation was performed by tracheal intubation 5 min after induction.The effect of pre-analgesia,postoperative sedation,hemodynamic indexes,surgical improvement indexes and application safety were observed by groups.Results There were 46 patients in each group.Pain visual analogue scores at 6,12 and 24 h in treatment group were 2.09±0.72,4.17±1.07 and 4.07±1.05,lower than those in control group,which were 2.61±1.03,4.76±1.27 and 4.65±1.11,the differences were statistically significant(all P＜0.05).The Ramsay sedation scores of the treatment group and the control group at 6 h after surgery were(2.85±0.62)and(2.11±0.73)points,respectively;the sedation scores of Ramsay at 12 h were 1.41±0.28 and 1.06±0.15,respectively.At 24 h,the sedation scores of Ramsay were 1.15±0.18 and 0.64±0.13,respectively,and the difference was statistically significant(P＜0.05).HR and MAP of treatment group and control group at T2 and T3 were significantly lower than those at T1 and T0(P＜0.05),there were no difference in HR and MAP between treatment group and control group at T2 and T3(P＜0.05).Operation time,recovery time after operation and intraoperative blood loss in treatment group were significantly lower than those in control group,and the differences were statistically significant(all P＜0.05).The success rate of 12-hour postoperative analgesia in test group and control group was 82.61％(38 cases/46 cases)and 63.04％(29 cases/46 cases),respectively,and the difference was statistically significant(P＜0.05).The adverse drug reactions in treament group and control group mainly included bradycardia,headache,dizziness and nausea,and the incidence of adverse drug reactions in treatment group and control group were 13.04％(6 cases/46 cases)and 8.70％(4 cases/46 cases),respectively,the difference was no statistically significant(P＜0.05).Conclusion Parecoxib sodium combined with dexmedetomidine preemptive analgesia has significantly improved analgesia and sedative effects in modified radical mastectomy for breast cancer,can prolong sedation and analgesia time,and stably control the perioperative hemodynamics of patients.

Objective To analyze the effect of low-dose methylprednone sodium succinate combined with erythromycin in the treatment of Mycoplasma pneumoniae infection with elevated lactate dehydrogenase(LDH)in children.Methods Children with Mycoplasma pneumoniae pneumonia(MPP)complicated with elevated LDH were divided into control group and treatment group by random number table method.The control group was given erythromycin treatment,and the treatment group was given low-dose methylprednisolone sodium succinate combined with erythromycin treatment.Clinical efficacy and clinical symptom disappearance time were recorded in both groups.Pulmonary X-ray signs,immune function[T cell subsets(CD4+,CD8+,CD4+/CD8+)],immunoglobulin(Ig)A,IgM and serum LDH were compared between the two groups before and after treatment,and the adverse drug reactions of treatment were observed.Results There were 51 cases in control group and 51 cases in treatment group.The total effective rate in treatment group was 96.00％,which was significantly higher than 81.63％in control group(P＜0.05).The fever abatement times in treatment group and control group were(4.22±0.87)and(5.46±0.98)d;cough disappearance times were(6.31±0.98)and(7.49±1.10)d;disappearance times of pulmonary rales were(7.36±1.14)and(8.61±1.23)d,all with significant difference(all P＜0.05).After treatment,the patchy infiltrating shadow sign rates in treatment group and control group were 2.00％and 16.33％;the bronchial wall thickening sign rates were 4.00％and 18.37％,all with significant difference(all P＜0.05).After treatment,IgA levels in treatment group and control group were(0.55±0.11)and(0.68±0.12)g·L-1;IgM levels were(0.90±0.19)and(1.18±0.21)g·L-1;LDH levels were(229.45±10.30)and(240.18±11.17)U·L-1,all with significant difference(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 6.00％and 4.08％respectively,without significant difference(P＞0.05).Conclusion Erythromycin combined with low-dose methylprednone in systemic treatment of children with MPP and elevated LDH has a significant efficacy,and it can promote the reductions of inflammation and immune disorders and accelerate the disease outcomes,and it is safe and reliable.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans). Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test. Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20 μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.