Objective:To investigate the clinicopathological features, treatment and prognosis of neuroendocrine carcinoma of the breast.Methods:Clinical data of 26 patients with neuroendocrine carcinoma of the breast admitted to the Northern Jiangsu People's Hospital from July 2013 to Mar 2021 were analyzed.Results:All 26 cases were female, the average aged of (62.81±11.95) years, the first clinical manifestations were painless breast masses, the average size being of (23.34±9.47) mm. At the time of diagnosis, regional lymph node metastasis was found in 4 cases, 1 case developed distant metastasis. Most patients' were on stage Ⅱ by TNM staging, molecular typing was Luminal A, and invasive mammary carcinoma with neuroendocrine differentiation was most common, with positive rates of ER and PR of 96%, the positive rate of CgA and Syn were 69% and 100%, and there was not positive expression of HER2. All patients received surgical treatment, 25 patients underwent postoperative adjuvant therapy. Twenty-five patients were followed up for a median follow-up time of 39.50 months. During the follow-up, 3 cases developed distant metastasis, 1 case died, the mean survival time was (40.81±26.90) months, there was ao satistically significant difference compared with invasive mammary carcinoma ( t=1.291, P=0.209). The mean disease free interval is (39.96±27.58) months. The overall survival and disease free survival at 1, 2 and 5 years are 100%, 100% and 87%, respectively. Conclusions:Neuroendocrine carcinoma of the breast occurs more frequently in elderly women, often with large tumor size, low rate of regional lymph node and distant metastasis, moderate histological grade, early clinical stage, and the molecular typing is mostly Luminal A.The overall prognosis is fair.

Objective:To explore the role of parental origin verification in chromosomal microarray analysis (CMA) on the determination of the clinical significance of copy number variations (CNVs).Methods:This retrospective study collected clinical information from 73 core families who underwent prenatal diagnosis at Peking University First Hospital from November 2017 to December 2019. Indications for prenatal diagnosis included ultrasound abnormality in 54 cases (including 12 with thickened nuchal translucency (≥2.5 mm), four with fetal growth restriction, seven with abnormal pregnancy history, and 31 with isolated ultrasound abnormality), NIPT indicated high-risk in four cases, advanced age in nine cases, abnormal pregnancy history alone in three cases, intrauterine death in two cases and one with maternal mental retardation. Genomic DNA of amniotic fluid sample, chorionic villi, cord blood, fetal tissues, and fetal heart blood were extracted using genomic DNA extraction kit. The CNVs of prenatal samples in 73 subjects were analyzed using array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array). Peripheral blood DNA of the couples, and relevant families if necessary, were collected and analyzed in the same way. The results of parental origin detection in CMA were summarized.Results:A total of 76 CNVs were detected in these 73 samples, out of which nine were pathogenic and parental origin detection revealed that six were de novo, two were maternally, and one was paternally inherited; six CNVs were likely pathogenic, including three de novo, two maternally inherited and one paternally inherited; 20 CNVs were variants of uncertain significance, including five paternally inherited, three maternally inherited and 12 de novo; 41 CNVs were likely benign, among which 38 were inherited from parents with normal phenotype. Conclusions:Parental origin verification plays an important role in explaining the clinical significance of detected fetal CNVs and thereby can help to analyze its clinical effect and reproductive risk.

OBJECTIVE: To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing. METHODS: Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree. RESULTS: NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene. CONCLUSION The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.
Adaptor Proteins, Signal Transducing/genetics* ; Apoptosis Regulatory Proteins/genetics* ; Charcot-Marie-Tooth Disease/genetics* ; Child ; Female ; Fibula/abnormalities* ; Homozygote ; Humans ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

OBJECTIVE: To explore the effects of nano-silicon dioxide( SiO_2) on the survival and poly( ADP-ribose)polymerase-1( PARP-1) expression in human bronchial epithelial cells( 16 HBE cells). METHODS: i) The 16 HBE cells were treated with nano-SiO_2 at concentrations ranging from 0 to 100 mg/L for 24. 0 hours,and CCK-8 assay was used to examine cell viability. ii) The 16 HBE cells were divided into 6 groups: solvent control group( equal volume solvent treatment),micro-SiO_2 control group( treated with 20 mg/L micro-SiO_2),5,10,and 20 mg/L nano-SiO_2 groups( treated with the corresponding final dose of nano-SiO_2),and curcumin group. The curcumin group was given pretreatment with curcumin at a final concentration of 10 μmol/L for 2. 0 hours followed by treatment with a final concentration of 20 mg/L of nano-SiO_2. Cells in each group were harvested at time points of 4. 0,12. 0 and 24. 0 hours after treatment. The relative expression of PARP-1 mRNA and protein in 16 HBE cells was detected by quantitative real-time polymerase chain reaction and Western blotting respectively. RESULTS: i) The survival of 16 HBE cells decreased with increasing nano-SiO_2 treatment dose,showing a dose-effect relationship( P < 0. 01). ii) The expression of PARP-1 mRNA and protein in 16 HBE cells were dose-dependently decreased after nano-SiO_2 stimulation at the 12. 0 and 24. 0 hours time points( P < 0. 01). The expression of PARP-1 mRNA and protein in 5,10,and 20 mg/L nano-SiO_2 groups decreased at the above mentioned time points( P < 0. 05),compared with the solvent control group at the same time points. The expression of PARP-1 mRNA and protein in 20 mg/L nano-SiO_2 group was lower than that in the micro-SiO_2 control group at the same 12. 0 and 24. 0 hours time point( P < 0. 05). The above two indexes of cells were higher in curcumin group than that of 20 mg/L nano-SiO_2 group at the 12. 0 hours time point( P < 0. 05). CONCLUSION: Nano-SiO_2 stimulation can lead to decrease survival of 16 HBE cells in a dose-dependent manner and down-regulation of PARP-1 expression may be one of the mechanisms of proliferation and inhibition of 16 HBE cells induced by nano-SiO_2. Curcumin has certain protective effect on nano-SiO_2-induced 16 HBE cell injury.

Objective To study the influence of clinical nutritional support on the effects of mechanical ventilation (MV), and to find the factors affecting the outcome of patients undergoing MV. Methods A case-control study was conducted. The clinical data of 235 patients undergoing MV admitted to intensive care unit (ICU) of Tongde Hospital of Zhejiang Province from January 2015 to June 2017 were retrospectively analyzed. The patients were divided into two groups according to whether weaning successfully within 7 days. The clinical data of patients in the two groups were collected including gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, underlying disease, nutritional indicators, nutritional support, and complications. The outcome of withdrawal within 7 days was served as a dependent variable, all observed indicators were served as independent variables, and Logistic regression analysis was carried out to screen the influencing factors of the weaning results within 7 days. Results 235 patients undergoing MV were enrolled, 128 patients were successfully withdrawn within 7 days, and 107 were unsuccessfully withdrawn. Compared with the successful weaning group, the patients of weaning failure group were older, and had higher APACHEⅡ score and lower albumin (Alb) and hemoglobin (Hb), more patients with internal medical underlying diseases and receiving parenteral nutrition (PN) and mixed nutrition, and the incidences of secondary infection, vomiting, abdominal distension, abnormal bowel sound, gastric retention, and diarrhea were higher. However, there was no statistical significance in gender between the two groups. The variables of statistical significance in univariate analysis were enrolled in the multifactor analysis model showing that age [odds ratio (OR) = 1.269, 95% confidence interval (95%CI) = 1.119-1.439, P < 0.001], APACHEⅡ score (OR = 1.643, 95%CI = 1.423-1.897, P < 0.001), internal medical underlying diseases (OR = 6.298, 95%CI = 4.012-9.887, P < 0.001), secondary infection (OR = 8.323, 95%CI = 2.568-26.975, P < 0.001), abdominal distension (OR = 3.368, 95%CI = 1.586-7.152, P = 0.002), abnormal bowel sounds (OR = 2.856, 95%CI = 1.215-6.713, P = 0.017), gastric retention (OR = 1.996, 95%CI = 1.183-3.368, P = 0.010), diarrhea (OR = 3.035, 95%CI = 1.337-6.890, P = 0.008) were risk factors for unsuccessful weaning,and compared with PN, enteral nutrition (EN; OR = 0.191, 95%CI = 0.098-0.372, P < 0.001) and mixed nutrition (OR = 0.375, 95%CI = 0.150-0.938, P = 0.037) were protective factors of successful weaning. The gender, Alb and Hb before and after MV, vomiting, gastrointestinal hemorrhage were not associated with weaning outcome within 7 days. Conclusions Elder, high APACHEⅡ score, internal medical underlying diseases, or secondary infection, abdominal distension, abnormal bowel sounds, gastric retention, diarrhea were risk factors of weaning failure within 7 days in patients undergoing MV. Compared with PN, EN and mixed nutrition were protective factors for successful weaning. For patients undergoing MV, EN should be performed early in the case of full recovery, hemodynamic stability, and serious metabolic disorders.

Objective:To investigate the clinicopathological differences in laterally spreading tumor (LST) from the rectum and colon.Methods:Clinicopathological records of 198 patients with LST (116 cases in rectum,82 cases in colon) from the Second Xiangya Hospital of Central South University between January 2012 and January 2017 were evaluated.Results:A total of 198 colorectal LST were included.According to the endoscopic classification,nodular mixed type (LST-GM),homogeneous type (LST-GH),flat elevated type(LST-FE) and pseudodepressed type (LST-PD) were 127(64.1％),13(6.6％),41(20.7％) and 17(8.6％),respectively.LST-GM was predominant in the rectum (71.7％),while LST-FE was predominant in the colon (78.0％),with significant difference (P＜0.01).The mean size of LST was (52.03±35.62) mm or (25.37±11.56) mm in the rectum or the colon,with significant difference between them (P＜0.01).High grade intraepithelial neoplasia frequency was higher in the rectum than that in the colon (31.0％ vs 18.3％),while the low grade intraepithelial neoplasia frequency was lower in the rectum than that in the colon (61.2％ vs 75.6％) (both P＜0.05).The mean size of LSTGM and LST-GH diameter were larger in the rectum than that in the colon,and the malignant potential of LST-GM was higher in the rectum than that in the colon.The percentage of high grade intraepithelial neoplasia + invasive carcinoma was 41.8％ and 22.2％,respectively (both P＜0.05).LST in colon was mostly treated with endoscopic mucosal resection,while LST in rectum was treated by endoscopic submucosal dissection predominantly.Conclu sion:LSTs from the rectum and colon show different clinicopathological characteristics to some extent.LST-GM is predominant in the rectum,while LST-FE is predominant in the colon.The malignant potential of LST-GM is higher in the rectum than that in the colon.

OBJECTIVE:To study the effects of Clebopride(CBP)bioadhensive sustained-release tablets on experimental gas-tric ulcer and gastrointestinal motility disorder. METHODS:Gastric ulcer rat model was induced by ethanol and aspirin,and then divided into model group (normal saline),common tablet (CBP tablet 0.072 mg/kg) and sustained-release tablet high-dose and low-dose groups (CBP bioadhensive sustained-release tablet 0.072,0.036 mg/kg);normal rats were included in normal control group (normal saline);they were given relevant medicine intragastrically,twice a day for sustained-release tablet,three times a day for other. Ulcer area were observed 2 and 4 days after medication to calculate healing rate of ulcer(n=6). Gastrointestinal mo-tility disorder mice model was induced by atropine,and then divided into model group (normal saline),common tablet group (CBP tablet 0.1 mg/kg)and sustained-release tablet high-dose,medium-dose and low-dose groups(CBP bioadhensive sustained-re-lease tablet 0.1,0.05,0.025 mg/kg);normal mice were included in normal control group(normal saline);they were given rele-vant medicine intragastrically,once a day,for consecutive 3 days. The rate of gastric emptying and small intestinal propulsion were detected (n=6). RESULTS:Compared with normal control group,ulcer area of rats increased in model group;compared with model group,that of rats decreased in common tablet group and sustained-release tablet high-dose,low-dose groups,with statisti-cal significance (P<0.01);healing rates of gastric ulcer were 32.35%-48.24% 2 days after medication,and those were above 70% 4 days after medication. Compared with normal control group,the rate of gastric emptying and small intestinal propulsion in mice decreased in model group;compared with model group,those of mice increased in common tablet group and sustained-re-lease tablet high-dose,medium-dose,low-dose groups. The effects of sustained-release tablet high-dose and medium-dose groups were better than that of common tablet group;those difference had statistical significance (P<0.01 or P<0.05). CONCLU-SIONS:CBP bioadhensive sustained-release tablets have im-provement effects against gastric ulcer of rats and gastrointesti-nal motility disorder of mice.

Objective To evaluate the effect of two polymorphisms(rs761737 and rs2269058) of RNF8 and the interactions with cigarette smoking and alcohol consumption on sperm DNA fragment index (DFI)and primary male infertility .Methods Based on case-control design ,polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology was used to de-tect the genotype of rs761737 and rs2269058 in RNF8 between 332 primary male infertile patients (composed by 87 patients of azoospermia ,166 patients of oligoasthenozoospermia and 79 patients of normozoospermia ) and 329 controls ,and Sperm Chromatin Dispersion(SCD) assay was used to assess sperm DNA fragment index (DFI) .Results Genotype and allele frequencies distribution of rs761737 and rs2269058 between cases and controls had no statistically significant difference (P>0 .05) .Sperm DFI in infertile group (46 .2 ± 22 .3)% was significantly higher than that of control group (21 .4 ± 9 .2)% (P<0 .05) ,stratified analysis suggested that Sperm DFI in oligoasthenozoospermia group (50 .0 ± 22 .1)% was also significantly higher than that of normozoospermia group (38 .2 ± 20 .7)% .The statistic differences of Sperm DFI in individuals who carried different genotypes of rs 761737 and rs2269058 in oligoasthenozoospermia group and normozoospermia group had no statistically significant difference (P>0 .05) .There was an inter-action between RNF8 rs2269058 and Cigarettes smoking(P<0 .05 ,OR=2 .37 ,95% CI 1 .06-5 .27) .Conclusion Although RNF8 rs761737 and rs2269058 have no effects on primary male infertility and sperm DFI ,cigarettes smoking increase the risk of primary male infertility in individuals who carry RNF8 rs2269058 AC+AA genotype .Sperm DFI is an important test to assess sperm quali-ty ,it is vital to reveal the etiology of primary male infertility and provide therapy guidance to clinicians .