Objective To discuss the effect and related mechanism on epithelial?mesenchymal transition(EMT)process and invasive ability of the trophoblasts JEG?3 by targeted silencing of Notch?1 gene. Methods Notch?1?siRNA interference fragment was designed and synthesized to sta?bly transfect JEG?3 cells. Changes in the invasive ability of trophoblasts were detected by Transwell chamber invasion assay. The expressions of Notch?1 ,E?cadherin ,vimentin and EMT transcriptive regulators slug ,snail ,twist were analyzed in transfected trophoblasts by Western blot. Results The relative expression of Notch?1 protein in JEG?3 and the invasive ability of JEG?3 were significantly decreased after transfection with Notch?1?siRNA,the expression of the epithelial indictor E?cadherin was significantly increased while the mesenchymal indicator vimentin was de?creased with the reduction of EMT transcriptive regulators slug,snail and twist. Conclusion The invasion of trophoblasts was affected by targeted si?lencing of Notch?1 gene and Notch?1 can reduce the invasion of trophoblasts through influencing EMT process.

Objective To evaluate the effect of edge-to-edge technique of anterior mitral valve prolapse using transthoraeic echocardiography(TTE). Methods Nineteen patients with anterior mitral valve prolapse underwent randomized operation using edge-to-edge technique. The grade of mitral regurgitation(MR),mitral valve are (MVA), the diameter of left atrial(LAD) and left ventricle(LVD), left ventricular ejection fracion(LVEF) and pulmonary artery systolic pressure(PASP) were evaluated. Results All the patients with anterior mitral valve prolapse had severe MR before the operation whereas the degree of MR changed into absence to mild degree after the procedure. There were significant statistic differences between pre- and post edge-to-edge procedure:LAD(51.63±10.03)mm vs (44.79±9.22)mm, P = 0.000, LVD(59.37±8.29)mm vs (52.68±7.31)mm, P = 0.000 ; PASP (45.37±18.34)mm Hg vs (33.00± 9.43)mm Hg, P = 0.002,1 mm Hg = 0.133 kPa;MVA(4.13±0.24)cm<'2> vs (2.90±0.28)cm<'2>, P = 0.000,while LVEF changed little[(66.0±9.0)% vs (67.0±6.0) %, p = 0.751]. Conclusions The edge-to-edge technique is a simple and effective surgical method which can remain subvalve structure,restore the normal morphology of left atria,left ventricle and maintain the function of left ventricle.

The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Intellectual developmental disorder with behavioral abnormalities and craniofacial malformations without epilepsy (IDDBCS). METHODS: A child who had visited the Lianyungang Maternal and Child Health Care Hospital in April 2021 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of his family members. RESULTS: The child, a 3-year-and-4-month-old male, had presented with global developmental delay and cranial malformation. Genetic testing revealed that he has harbored a heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene, for which both of his parents were of the wild type. This low-frequency variant may alter the structure and function of the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting). CONCLUSION The heterozygous c.1703delA (p.K568Sfs9) variant of the PHF21A gene probably underlay the IDDBCS in this patient.
Child ; Male ; Humans ; Infant ; Developmental Disabilities/genetics* ; Craniofacial Abnormalities/genetics* ; Seizures/genetics* ; Intellectual Disability/genetics* ; Problem Behavior ; Mutation

Objective To study the therapeutic regimen for the simple third or fourth grade of traumatic spleen rupture in patients with hemorrhagic shock. Methods A total of 58 patients with traumatic spleen rupture complicated with hemorrhagic shock admitted between January 2012 and June 2016 were enrolled for analysis. The causes of the casualties suffering from closed abdominal injuries including 31 traffic accident, 13 falling down from a height, 8 tumbling on the ground, 2 beaten trauma and 4 other traumatic injuries. All the patients were divided into the conventional surgery group or proximal selective spleen artery embolization (PASE) group. Comparisons of surgery and postoperative relevant parameters between two groups were analyzed, and the curative effects of the two kinds of treatments was evaluated. Results There were no statistically significant difference in age, sex, degree of spleen rupture, systolic blood pressure, heart rate, and hemoglobin concentration between two groups (P＞ 0.05). The time consumed for operation (T1),the time required for systolic blood pressure recovery (T2), and the allogeneic blood volume capacity (V2) transfused in PASE group were significantly lesser than those in the conventional surgery group (P＜0.05), however there was no difference in the autologous blood volume reinfusion (V1) (P＞ 0.05). Furthermore, the incidence of fever, infection of incision, ileus, ICU treatment, time required fro intestinal function time and hospital stay in PASE group were significantly lesser than those in conventional surgery group (P＜0.05), but the incidence of left upper abdominal pain in PASE group was higher (P＜0.05). Conclusions Selective spleen artery embolization can rapidly stabilize hemodynamics, and shorten the operation time. It also can reduce the complications and allogeneic blood use, shorten recovery time and hospital stay. It is a preferential choice for treatment of traumatic spleen rupture with shock, and worth popularizing in clinical.

Objective To investigate the inhibitory effect and mechanism of Metformin (Met) combined with irradiation in CT26WT cell lines or mouse models with transplanted tumors.Methods CT26WT cell line was treated with 0.5 μmol/L,1.0 μmol/L,5.0 μmol/L and 10.0 μmol/L Met,and CellTiter Glo kit was used to detect the inhibitory effect of Met at different concentrations on the viability of CT26WT cells.CT26WT cell line was treated with the control,Met (10 pmol/L),15 Gy irradiation and 15 Gy irradiation+Met (10 μmol/L).Clone formation assay was employed to detect the cell proliferation activity.Bablc mouse models of transplanted tumors (tumor size＞ 150 mm3) were established and randomly divided into the control,15 Gy irradiation,Met and 15Gy irradiation+Met groups.Mice were given with 750 mg/kg Met at 24 h before irradiation.Transplanted tumor volume was measured regularly to delineate the growth curve of transplanted tumors and survival curve.The expression levels of P-H2AX and Sting proteins in CT26WT cells and transplanted tumors were detected by Western blot.The infiltration of CD8a (+) T cells in transplanted tumor tissues was detected by immunohistochemistry.Results The relative cell survival rate was 100％,87.9％,87.8％,87.3％ and 76.5％ in the 0,0.5,1.0,5.0 and 10.0μmol/L Met groups,respectively (all P＜0.05).The inhibitory effect of 10.0 μmol/L was significantly stronger than that of 5.0 μmol/L (P＜0.001).The colone formation rate 34.0％,24.0％,22.3％ and 14.0％ in the control,Met,15 Gy irradiation,Met+ 15Gy irradiation groups,respectively (all P＜0.001).Western blot showed that compared with the control group,the expression of Sting protein was increased by 2.99-fold after Met treatment (P＜0.001),and increased by 1.37-fold and 4.41-fold in the 15 Gy irradiation and 15Gy irradiation+Met groups (both P＜0.01).Compared with the 15 Gy irradiation group,the expression of P-H2AX protein was significantly increased by 1.43 times after treatment with 15Gy+Met (P＜0.001).The transplanted tumor growth curve showed that the transplanted tumor growth in the 15 Gy+Met group was slower than that in the control group[(1007.0± 388.5) mm3 vs.(2639.0± 242.9) mm3,P＜ 0.05)].The overall survival time in the 15 Gy irradiation+Met group was 48 d,significantly longer than 32 d in the control group (P＜0.001).Compared with the control group,the expression of P-H2AX and Sting proteins in the 15 Gy+ Met group was increased by 8.8-fold and 1.6-fold (both P＜0.001).Immunohistochemical staining showed that the infiltration of CD8a (+) T cells in the 15 Gy irradiation+Met group was significantly higher than that in the control group (P＜0.01).Conclusions Met combined with radiotherapy can inhibit the proliferation and clone formation of colon cancer cells,probably by aggravating DNA damage and activating the Sting signaling pathway,eventually leading to the increase of CD8a (+) T cells in tumor tissues and enhancing the killing effect upon transplanted tumor cells.

Objective:To evaluate the ophthalmic service ability of county hospitals in China based on the improved DS evidence theory.Methods:Convenient sampling method was used to select the data of ophthalmology department of 9 county hospitals in eastern, central and Western China in 2019. The improved DS evidence theory method based on Mahalanobis distance weight coefficient was applied to evaluate the medical service ability, and the evaluation results were compared with the classical evidence theory method.Results:The regional development of ophthalmic service capacity in counties of China was uneven, and there were regional differences in the evaluation results of some indicators. Hospitals in the eastern region were generally leading in the evaluation of a number of indicators related to the amount of medical services. The numbers of inpatient operations, outpatient operations, bed turnover times, bed utilization rate, number of inpatients, number of outpatients, number of patients in the eastern region were 3.25, 1.60, 1.81, 1.61, 2.64, 2.63 and 4.47 times of the numbers of hospitals in western region. Compared with the classical evidence theory method, the analysis results of the improved DS evidence theory method were consistent with the actual business development of each hospital, and the evaluation results were credible, which could more effectively reduce the uncertainty in the evaluation results.Conclusions:Ophthalmic service ability of county hospitals in China needs to be continuously improved. Improved DS evidence theory can be adopted to make continuous evaluation.

Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Objective:To explore the value of pre-treatment contrast-enhanced computed tomography (CT)-based texture analysis in predicting response to non-small cell lung cancer (NSCLC) immunotherapy.Methods:From January to July 2018, a total of 51 lesions from 42 patients with advanced non-small cell lung cancer receiving immunotherapy at Shanghai Chest Hospital were selected in this retrospective study. Pre-treatment contrast-enhanced CT-based texture features were extracted by MaZda software. Ten optimal texture features were chosen based on three different methods: Fisher coefficient, mutual information measure (MI) and minimization of classification error probability combined average correlation coefficients(POE+ ACC), respectively. According to the efficacy of the first immunotherapy, 51 lesions were divided into non-progressive disease (non-PD, n=26) and progressive disease (PD, n=25). The differences were tested in each texture feature set between the two groups. The immunotherapy effects of target lesions were analyzed by principal component analysis(PCA), linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA). The sensitivity, specificity, accuracy, positive-predictive value (PPV) and negative-predictive value (NPV) were calculated. The area under the curve (AUC) was used to quantify the predictive accuracy of the three analysis models for each texture feature set and compare them with the actual classification results. Results:In all of three texture feature sets, the texture parameter differences of Perc.50%, Perc.90%, "S(5, 5)SumEntrp" and "S(4, 4)SumEntrp" were higher in PD group than those in non-PD group (all P<0.05). The classification result of texture feature set chosen by POE+ ACC and analyzed by NDA was identified as the best model (AUC=0.802, 95% CI: 0.674-0.930), and its sensitivity, specificity, accuracy, PPV and NPV were 72%, 88.5%, 80.4%, 85.7%, 76.7%, respectively. Conclusion:Pre-treatment contrast-enhanced CT-based texture characteristics of NSCLC may function as non-invasive biomarkers for the evaluation of response to immunotherapy.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.