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Objective: To investigate the effect of phosphocreatine (PCr) on angiotensin II (Ang II) induced proliferation and collagen synthesis of cardiac ifbroblasts in neonatal rats with its mechanism.
Methods: The cardiac ifbroblasts (CF) from neonatal rats were cultured in vitro and were divided into 4 groups.①Control group, the CF was cultured in non-serum DMEM,②Ang II group, the CF was cultured with Ang II at (1×10-6) mol/L,③PCr treated group, the CF was cultured with PCr at 10 mmol/L, and④Ang II+PCr group. The CF cell cycle percentage was detected by lfow cytometric assay, myocardial collagen content was observed by VG staining and protein expression of phosphorylated extracellular signal-regulated kinase (pERK1/2) was detected by immuneohistochemistry.
Results: ① Compared with Control group, the CF in Ang II group showed increased percentage of S phase and decreased percentage of G0/G1 and G2/M phases, increased collagen content and pERK1/2 protein expression, all P<0.01.② The CF cell cycle, collagen content and pERK1/2 protein expression were similar between Control group and PCr treated group, all P>0.05. ③ Compared with Control group, Ang II + PCr group had elevated pERK1/2 protein expression, P<0.01, while the CF cell cycle and collagen content were similar with Control group, P>0.05.④Compared with Ang II group, the CF in Ang II + PCr group had increased percentage of G0/G1 and G2/M phases, decreased percentage of S phase, decreased collagen content and pERK1/2 protein expression, all P<0.01.
Conclusion: PCr may partially inhibit Ang II induced CF proliferation and collagen synthesis which might be related to the inhibition of excessively activated ERK1/2. Therefore, PCr could improve Ang II induced myocardial ifbrosis in neonatal rats.

OBJECTIVETo explore the reasonable therapeutic strategy for different types of epicanthus.

METHODSPatients with epicanthus were classificated according to the shape, extent and inner canthal distance and treated with different methods appropriately. Modified asymmetric Z plasty with two curve method was used in lower eyelid type epicanthus, inner canthus type epicanthus and severe upper eyelid type epicanthus. Moderate upper epicanthus underwent '-' shape method. Mild Upper epicanthus in two conditions which underwent nasal augumentation and double eyelid formation with normal inner canthal distance need no correction surgery. The other mild epicanthus underwent '-' shape method.

RESULTSA total of 66 cases underwent the classification and the appropriate treatment. All wounds healed well. During 3 to 12 months follow-up period, all epicanthus were corrected completely with natural contour and unconspicuous scars. All patients were satisfied with the results.

CONCLUSIONSClassification of epicanthus hosed on the shape, extent and inner canthal distance and correction with appropriate methods is a reasonable therapeutic strategy.

Objectives: To study the changes of blood levels of soluble semaphorin 4D (sSema4D) and matrix metalloproteinases-14 (MMP-14);to explore the correlation between sSema4D and ventricular remodeling in patients of dilated cardiomyopathy with chronic heart failure.
Methods: Our research included in 2 groups:Dilated cardiomyopathy group, n=86 patients and Control group, n=32 healthy subjects. Blood levels of sSema4D, MMP14, Pro-BNP and hs-CRP were examined by ELISA. Left atrial diameter (LAD), right ventricular diameter (RVD), ejection fraction (EF), left ventricular end diastolic diameter (LVEDD), left ventricular fractional shortening (LVFS) were measured by echocardiography. Correlation analysis between blood levels of sSema4D, MMP-14 and the parameters for left ventricular remodeling was conducted.
Results: Blood levels of sSema4D and MMP14 were different between 2 groups, P<0.005. In Dilated cardiomyopathy group, sSema4D level was positively related to MMP-14 and LVEDD (r=0.462, P=0.001 and r=0.643, P<0.001) respectively.
Conclusion: Serum level of sSema4D might be related to ventricular remodeling in patients with dilated cardiomyopathy which could be used as risk factor for predicting the prognosis of heart failure in relevant patients.

Objective:To analyze the prognostic factors of robot-assisted radical cystectomy (RARC).Methods:The clinical data of 224 patients underwent RARC from December 2014 to December 2018 in Nanjing Drum Hospital were reviewed. There were 193 males and 31 females, aged 36-92 years, with mean of 68 years. There were 7 patients(3.1%)undergoing neoadjuvant chemotherapy, the ASA scores of 125 patients (55.8%) were more than 2, and the mean body mass index was 23.4(15.4-35.5)kg/m 2. All patients were treated with RARC, with 72(32.1%) patients undergoing intraoperative blood transfusion. Kaplan-Meier method was used to analyze recurrence-free survival rate (RFS), cancer-specific survival rate (CSS) and overall survival rate (OS). Cox multivariate risk ratio model was used to evaluate the correlation between survival outcome and perioperative and pathological factors in patients treated with RARC. Results:For pathological status, there were 82 of ≤T 1, 64 of T 2, 57 of T 3 and 21 of T 4. Of all the patients, 49(21.9%) had lymph node metastasis, 12(5.4%) had positive surgical margin, 82(36.6%) had lymphovascular invasion(LVI), and 41(18.3%) underwent adjuvant chemotherapy. Follow-up time was between 11-60 months, and the median follow-up time was 24 months. The 5-year cumulative OS, RFS and CSS were 57.15%, 48.84% and 59.60%, respectively. Univariate Cox regression analysis showed that T stage( HR=5.764, 95% CI 1.926-17.249, P=0.002; HR=4.086, 95% CI 1.611-10.364, P=0.003; HR=9.391, 95% CI 2.118-41.637, P=0.003), N stage( HR=6.446, 95% CI 3.438-12.087, P<0.001; HR=5.661, 95% CI 3.086-10.385, P<0.001; HR=5.980, 95% CI 2.982-11.992, P<0.001), LVI( HR=3.319, 95% CI 2.008-5.486, P<0.001; HR=2.894, 95% CI 1.782-4.701, P<0.001; HR=3.471, 95% CI 2.017-5.974, P<0.001), American Society of Anesthesia (ASA)score( HR=2.888, 95% CI 1.619-5.150, P<0.001; HR=1.765, 95% CI 1.060-2.940, P=0.029; HR=2.612, 95% CI 1.424-4.792, P=0.002), body mass index( HR=0.886, 95% CI 0.819-0.957, P=0.002; HR=0.885, 95% CI 0.819-0.955, P=0.002; HR=0.862, 95% CI 0.792-0.938, P=0.001), age( HR=1.580, 95% CI 1.250-1.997, P<0.001; HR=1.362, 95% CI 1.088-1.705, P=0.007; HR=1.530, 95% CI 1.190-1.968, P=0.001) and intraoperative blood transfusion( HR=1.899, 95% CI 1.160-3.108, P=0.011; HR=2.218, 95% CI 1.371-3.587, P=0.001; HR=2.227, 95% CI 1.312-3.782, P=0.003) were significantly related to survival outcome. Multivariate Cox regression analysis showed that T stage( HR=4.506, 95% CI 1.433-14.175, P=0.01; HR=3.159, 95% CI 1.180-8.454, P=0.022; HR=7.810, 95% CI 1.674-36.444, P=0.009), N stage( HR=6.096, 95% CI 2.981-12.467, P<0.001; HR=5.368, 95% CI 2.683-10.740, P<0.001; HR=5.539, 95% CI 2.497-12.288, P<0.001) and ASA score( HR=6.180, 95% CI 2.371-16.110, P<0.001; HR=2.702, 95% CI 1.175-6.215, P=0.019; HR=6.471, 95% CI 2.290-18.286, P<0.001) were independent predictors of RFS, CSS and OS, and adjuvant chemotherapy( R=0.434, 95% CI 0.202-0.930, P=0.032) could only predict OS. Conclusion:T stage, N stage and ASA were main independent predictors of postoperative survival outcomes, and adjuvant chemotherapy was independent predictor of OS.

Objective: To investigate the epidemic status and influencing factors of colorectal polyps among urban residents in Lanxi. Methods: A representative urban community was selected from Lanxi. A total of 935 local residents aged 18-80 years received questionnaire survey,physical examination,laboratory tests and colonoscopy. Multivariate Logistic regression analysis was applied to exam the potential influencing factors for colorectal polyps. Results : Eventually 880 residents were involved into the statistical analysis. Colorectal polyps were detected in 167 participants with a crude prevalence of 18.98% and adjusted prevalence for age and gender of 13.28%. The prevalence of colorectal polyps in men（28.70%）was significantly higher than that in women（12.92%,P<0.05）. The results of logistic regression analysis showed that age（OR=1.038,95%CI：1.018-1.057）,males（OR=1.919,95%CI：1.303-2.826）,the middle school level of education（OR=2.443,95%CI：1.507-3.961）and constitution of Yin-Asthenia（OR=0.203,95%CI：0.057-0.720）were influencing factors for colorectal polyps;among male participants,hypertension（OR=1.721,95%CI：1.018-2.908）was a risk factor for colorectal polyps;among female participants,age（OR=1.076,95%CI：1.042-1.111）,BMI（OR=1.099,95%CI：1.001-1.207）,the middle school level of education（OR= 3.507,95%CI：1.794-6.856）and constitution of Yin-Asthenia（OR=0.160,95%CI：0.033-0.770）were influencing factors for colorectal polyps. Conclusion Age,sex,education level and constitution of Yin-Asthenia were associated with the risk of colorectal polyps among residents in Lanxi;hypertension was associated with the risk of colorectal polyps in males,while age,BMI,education level and constitution of Yin-Asthenia were associated with the risk of colorectal polyps in females.

Objective: To identify the functional connectivity characteristics of insula, sensory and social related brain regions in boys with autism spectrum disorder(ASD), to explore the central nervous basis of sensory abnormality affecting core symptoms in boys with ASD. Methods: Resting state functional magnetic resonance imaging (rs fMRI) data were collected from 34 boys with ASD and 29 typical development boys (TD group). Based on functional connectivity analysis, the sensory related brain regions, insula, and social related brain regions were taken as regions of interest to calculate the functional connectivity (FC) level between the regions of interest, the differences between the two groups were compared and the results were corrected by FDR. The Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS) and Autism Spectrum Quotient-Children s Version (AQ-Child) were used to assess the core phenotypes of boys with ASD. Results: Compared with the TD group, the levels of FC between tactile brain regions and insula, olfactory brain regions and insula, auditory brain regions and insula in boys with ASD group were significantly increased. The level of FC between the insula and bilateral amygdala，insula and the medial prefrontal cortex(mPFC) were significantly increased( P <0.05).Pearson correlation analysis showed that the level of FC between auditory brain region(BA42)and left insula in ASD group was negatively correlated with the scores of communication subscale of ADOS( r =-0.44)，social interaction subscale of ADOS( r =-0.43), communication & social interaction subscale of ADOS( r =-0.49),attention to details subscale of AQ-Child( r =-0.41). The level of FC between the right insula and right amygdala was positively correlated with the attention switch subscale of AQ-Child( r =0.38), the level of FC between right insula and mPFC was positively correlated with the scores of repetitive behavior subscale of ADOS( r =0.48), the attention switch subscale of AQ-Child( r =0.49), total scale subscale of AQ-Child( r =0.41), total scale of CARS( r =0.41)( P < 0.05 ). Conclusion The levels of FC between insula and sensory related, social related brain regions are abnormal in children with ASD, which have significant correlations with clinical symptoms. In depth studies can be conducted to explore underlying neutral mechanisms.

OBJECTIVE: To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure. METHODS: The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants. RESULTS: In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively. CONCLUSION The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.
Epilepsy/genetics* ; Female ; Filamins/genetics* ; Heterozygote ; Humans ; Magnetic Resonance Imaging ; Mutation ; Periventricular Nodular Heterotopia/genetics* ; Seizures

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

OBJECTIVE: To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions. METHODS: All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend. RESULTS: Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05). CONCLUSION Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.
Pregnancy ; Humans ; Female ; Aged ; Abortion, Spontaneous/genetics* ; DNA Copy Number Variations ; Chromosome Aberrations ; Chromosome Disorders/genetics* ; Aneuploidy ; Abortion, Habitual/genetics*