The incidence of surgical site infections in China.

Surgical site infections (SSIs) are a common type of healthcare-associated infection. We performed a literature review to demonstrate the incidence of SSIs in mainland China based on studies since 2010. We included 231 eligible studies with ≥30 postoperative patients, comprising 14 providing overall SSI data regardless of surgical sites and 217 reporting SSIs for a specific site. We found that the overall SSI incidence was 2.91% (median; interquartile range: 1.05%, 4.57%) or 3.18% (pooled; 95% confidence interval: 1.85%, 4.51%) and the SSI incidence varied remarkably according to the surgical site between the lowest (median, 1.00%; pooled, 1.69%) in thyroid surgeries and the highest (median, 14.89%; pooled, 12.54%) in colorectal procedures. We uncovered that Enterobacterales and staphylococci were the most common types of micro-organisms associated with SSIs after various abdominal surgeries and cardiac or neurological procedures, respectively. We identified two, nine, and five studies addressing the impact of SSIs on mortality, the length of stay (LOS) in hospital, and additional healthcare-related economic burden, respectively, all of which demonstrated increased mortality, prolonged LOS, and elevated medical costs associated with SSIs among affected patients. Our findings illustrate that SSIs remain a relatively common, serious threat to patient safety in China, requiring more action. To tackle SSIs, we propose to establish a nationwide network for SSI surveillance using unified criteria with the aid of informatic techniques and to tailor and implement countermeasures based on local data and observation. We highlight that the impact of SSIs in China warrants further study.

SARS-CoV-2 and male infertility: from short- to long-term impacts.

PURPOSE: The coronavirus 2019 (COVID-19) pandemic-caused by a new type of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-has posed severe impacts on public health worldwide and has resulted in a total of > 6 million deaths. Notably, male patients developed more complications and had mortality rates ~ 77% higher than those of female patients. The extensive expression of the SARS-CoV-2 receptor and related proteins in the male reproductive tract and the association of serum testosterone levels with viral entry and infection have brought attention to COVID-19's effects on male fertility. METHODS: The peer-reviewed articles and reviews were obtained by searching for the keywords SARS-CoV-2, COVID-19, endocrine, spermatogenesis, epididymis, prostate, and vaccine in the databases of PubMed, Web of Science and Google Scholar from 2020-2022. RESULTS: This review summarizes the effects of COVID-19 on the male reproductive system and investigates the impact of various types of SARS-CoV-2 vaccines on male reproductive health. We also present the underlying mechanisms by which SARS-CoV-2 affects male reproduction and discuss the potentially harmful effects of asymptomatic infections, as well as the long-term impact of COVID-19 on male reproductive health. CONCLUSION: COVID-19 disrupted the HPG axis, which had negative impacts on spermatogenesis and the epididymis, albeit further investigations need to be performed. The development of vaccines against various SARS-CoV-2 variations is important to lower infection rates and long-term COVID risks.

[Bioinformatics analysis of primary biliary cholangitis key genes and molecular mechanisms].

Objective: To extract the differentially expressed key genes of primary biliary cholangitis (PBC) using bioinformatics methods, so as to provide information for further study into the mechanism. Methods: The GSE119600 dataset was downloaded from the GEO database to obtain differentially expressed genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Protein-protein interaction (PPI) network reconstruction, Cytoscape software visualization, and core gene screening were performed. The area under the receiver operating characteristic curve (ROC AUC) was used to assess the diagnostic effectiveness of genes and plot the pROC software package. The x-Cell software was used to calculate the enrichment score of 34 immune cells in each sample. Finally, four key genes (PSMA4, PSMA1, PSMB1, and PSMA3) were selected. Blood samples were analyzed using the qPCR method. Results:: A total of 373 immune-related differentially expressed genes were identified. Eight genes (PSMC6, PSMB2, PSMB1, PSMA3, PSMA4, PSMA1, PSMD7, and PSMB5) were screened from the 178 nodes and 596 edges as hub genes of the PPI network, which were significantly related to amino acid metabolism, hematopoietic stem cell differentiation, cell cycle, and immune processes. PSMA4, PSMA1, PSMB1, and PSMA3 were defined as immunological biomarkers for PBC with an AUC value of the ROC curve > 0.7. Immunoinfiltrating cell analysis showed that the proportion of eosinophils was significantly higher in PBC patients compared to the control group, whereas the proportion of CD4+ memory T cells, plasma cells, Th2 cells, and cDC cells was significantly lower in PBC patients than the control group. Plasma cells were associated with all four immunological biomarkers. Seven PBC patients and seven healthy subjects were selected for peripheral blood qPCR validation, which demonstrates that PSMB1, PSMA3, PSMA1, and PSMA4 levels were significantly lower in PBC patients than healthy subjects, with a statistically significant difference. Conclusion:: Bioinformatics screened eight key genes, of which four were key immunological markers and may serve as a basis for clinical diagnosis and mechanism exploration.

[Clinical study of digital six-axis external fixation frame based on CT data for tibiofibular fractures].

Objective: To investigate the clinical effect of applying the digital six-axis external fixation frame based on CT data in the treatment of tibiofibular fractures. Methods: The clinical data of 43 patients with tibiofibular fractures treated by the self-developed digital six-axis external fixation frame based on CT data at Integrated Orthopedic Department of Traditional Chinese Medicine (TCM) and Western Medicine,HongHui Hospital from January 2018 to January 2021 were retrospective analysis.There were 27 males and 16 females,aged (36.0±9.4) years(range:25 to 50 years).AO classification:15 cases of 42A,11 cases of 42B, and 17 cases of 42C.There were 7 open fractures and Gustilo fracture classification:2 cases of type Ⅰ,4 cases of type Ⅱ,and 1 case of type Ⅲ.The two or three plane rings were connected with six connecting rods to form a complete six-axis external fixation frame,and the distal and proximal fracture blocks were connected to the distal and proximal rings by fixation pins,and the lengths of the six connecting rods needed to be adjusted were calculated by using the supporting software according to the CT data after surgery,and then the lengths of the connecting rods were adjusted one by one to complete the reduction of the fracture. The reduction accuracy of this six-axis external fixation brace was evaluated by measuring postoperative radiographs; postoperative recovery and complications were collected,the time of brace removal was recorded,and the function of the affected limb was evaluated according to the Johner-Wruhs score at the final follow-up. Results: Postoperative radiographs showed that all patients achieved satisfactory reduction with lateral displacement(M(IQR)) of 2.3(2.5) mm (range:0.3 to 7.3 mm),anteroposterior displacement of 2.1 (2.4) mm (range:0.3 to 5.7 mm),anteroposterior angulation of 2.5(2.4)°(range:0 to 5°),internal and external angulation of 2.1(1.5)°(range:0 to 4°), and no significant internal or external rotational deformity was detected on the exterior.On the second postoperative day,all patients were able to walk with partial weight-bearing on crutches. All 43 patients were followed up for more than 6 months,with a follow-up period of (33.3±7.3) weeks (range:24 to 42 weeks).The external fixation frame was removed after the fracture healed.The external frame was removed at 20(3)weeks (range:18 to 25 weeks) postoperatively. Up to the final follow up, no secondary fracture occurred in any of them.The Johner-Wruhs score of the affected limb at the last follow-up was excellent in 39 cases and good in 4 cases. Conclusion: The digital six-axis external fixator based on CT data for tibiofibular fractures has the advantages of precise reduction,firm fixation,simple operation,rapid fracture healing,and minimal trauma, which is a minimally invasive method for treating tibiofibular fractures,especially suitable for patients with poor skin and soft tissue conditions such as open injuries.

[Early reduction of serum RANTES can predict HBsAg clearance in patients with chronic hepatitis B treated with nucleos(t)ide analogues combined with peginterferon alpha].

Objective: To observe the dynamic changes of serum RANTES during the treatment with nucleos(t)ide analogues combined with pegylated interferon alpha (peginterferon-α), and further analyze the predictive effect of RANTES on HBsAg clearance in patients with chronic hepatitis B. Methods: 98 cases of chronic hepatitis B with quantitative HBsAg < 3 000 IU/ml and HBV DNA < 20 IU/ml after≥1 year NAs treatment were enrolled. Among them, 26 cases continued to receive NAs monotherapy, 72 cases received NAs combined with pegylated interferon alpha therapy. The changes in RANTES during treatment were observed. The receiver operating characteristic curve was used to analyze the early changes of RANTES to predict the HBsAg clearance during 48 weeks. Results: During 48 weeks, 15 cases (20.83%) had achieved HBsAg clearance in combination group, while no patient had achieved HBsAg clearance in NAs group. The overall serum RANTES level had decreased from baseline in NAs and combination group. At week 48, in the combination group, the serum RANTES level was decreased more significantly in patients with HBsAg clearance than patients without. Further analysis showed that, in combination group, HBsAg clearance rate of patients with serum RANTES decreased at week 12 and 24 was higher than patients with elevated (29.17% vs. 4.17%, P = 0.014; 28.00% vs. 4.55%, P = 0.052), and quantitative HBsAg reduction was larger significantly [(1.49 ± 1.26) log(10)IU/ml vs. (0.73 ± 0.81) log(10)IU/ml, P = 0.017; (1.54 ± 1.27) log(10)IU/ml vs. (0.57 ± 0.56) log(10)IU/ml, P = 0.004]. Receiver operating characteristic curve analysis showed that the baseline quantitative HBsAg and the reduction in quantitative HBsAg and serum RANTES during the early period were predictors of HBsAg clearance after 48-week combination therapy. Furthermore, the combination of baseline quantitative HBsAg and 12 - or 24-week reduction of serum RANTES were better predictors of HBsAg clearance than that of baseline quantitative HBsAg combined with HBsAg decrease at week 12 or 24. The area under the receiver operating characteristic curve of the former was 0.925 and 0.939, while that of the latter was 0.909 and 0.929, respectively. Conclusion: Early reduction of serum RANTES at week 12 and 24 can predict HBsAg loss in CHB patients receiving addition of peginterferon-α to ongoing NAs Therapy, so serum RANTES could be one of the key immunological markers for predicting HBsAg clearance.

[Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation].

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

Development of a dynamic food chain model for assessment of the radiological impact from radioactive releases to the aquatic environment.

The software tool POSEIDON-R was developed for modelling the concentration of radionuclides in water and sediments as well as uptake and fate in the aquatic environment and marine organisms. The software has been actively advanced in the aftermath of the Fukushima Dai-ichi accident. This includes development of an uptake model for the benthic food chain, a kinetic-allometric compartment model for fish and recent advancements for the application of 3H. This work will focus on the food chain model development and its extension to key artificial radionuclides in radioecology such as 3H. Subsequently, the model will be applied to assess the radiological dose for marine biota from 3H, 90Sr, 131I, 134Cs and 137Cs released during and after the Fukushima Dai-ichi accident. The simulation results for 3H, 90Sr, 131I, 134Cs and 137Cs obtained from the coastal box (4-4 km) located at the discharge area of the Fukushima Dai-ichi NPP, and the surrounding regional box (15-30 km) are compared with measurements. The predictions are by and large consistent with experimental findings, although good validation for 3H, 90Sr and 131I is challenging due to lack of data. On the basis of the model predictions a dose assessment for pelagic and benthic fish is carried out. Maximum absorbed dose rates in the coastal box and the regional box are respectively 6000 and 50 µGy d-1 and are found in the pelagic non-piscivorous fish. Dose rates exceeding ICRP's derived consideration levels of 1 mGy d-1 are only found in the direct vicinity of the release and shortly after the accident. During the post-accidental phase absorbed dose rates consistently fall to levels where no deleterious effects to the marine biota are expected. The results also demonstrate the prolonged dose rate from 134Cs and 137Cs, particularly for benthic organisms, due to caesium's affinity with sediment, re-entry of caesium from the sediment into the food chain and external exposure from its high energetic gamma emissions. Uptake of non-organic tritium (HTO) and organically bound tritium (OBT) is modelled and shows some accumulation of OBT in the marine organism. However, dose rates from tritium, even during the accident, are low.

Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect.

OBJECTIVE: To evaluate comprehensively, using chromosomal microarray analysis (CMA) and exome sequencing (ES), the prevalence of chromosomal abnormalities and sequence variants in unselected fetuses with congenital heart defect (CHD) and to evaluate the potential diagnostic yields of CMA and ES for different CHD subgroups. METHODS: This was a study of 360 unselected singleton fetuses with CHD detected by echocardiography, referred to our department for genetic testing between February 2018 and December 2019. We performed CMA, as a routine test for aneuploidy and copy number variations (CNV), and then, in cases without aneuploidy or pathogenic CNV on CMA, we performed ES. RESULTS: Overall, positive genetic diagnoses were made in 84 (23.3%) fetuses: chromosomal abnormalities were detected by CMA in 60 (16.7%) and sequence variants were detected by ES in a further 24 (6.7%) cases. The detection rate of pathogenic and likely pathogenic genetic variants in fetuses with non-isolated CHD (32/83, 38.6%) was significantly higher than that in fetuses with isolated CHD (52/277, 18.8%) (P < 0.001), this difference being due mainly to the difference in frequency of aneuploidy between the two groups. The prevalence of a genetic defect was highest in fetuses with an atrioventricular septal defect (36.8%), ventricular septal defect with or without atrial septal defect (28.4%), conotruncal defect (22.2%) or right ventricular outflow tract obstruction (20.0%). We also identified two novel missense mutations (c.2447G>C, p.Arg816Pro; c.1171C>T, p.Arg391Cys) and a new phenotype caused by variants in PLD1. CONCLUSIONS: Chromosomal abnormalities were identified in 16.7% and sequence variants in a further 6.7% of fetuses with CHD. ES should be offered to all pregnant women with a CHD fetus without chromosomal abnormality or pathogenic CNV identified by CMA, regardless of whether the CHD is isolated. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

[Application of a new type of angle-adjustable osteotomy guide in closing wedge distal femoral osteotomy].

Objective: To explore the feasibility of fast and accurate osteotomy using a new angle adjustable osteotomy guide (AAOG) in closing wedge distal femoral osteotomy(CWDFO). Methods: The clinical data of 14 patients (17 knees) with valgus knee treated with CWDFO at Department of Integrated Chinese and Western Medicine Orthopedics, Honghui Hospital, Xi'an Jiaotong University from January 2018 to July 2019 were analyzed retrospectively. There were 3 males and 11 females, aging (41.4±16.4) years (range: 18 to 56 years). The body mass index was (23.5±3.5) kg/m(2) (range: 18.1 to 28.9 kg/m(2)). The guide pins were placed with the assistance of the self-designed AAOG. Before the surgery, Solidworks software was used to calculate the correction angle and the osteotomy radius accurately. The osteotomy guide was adjusted according to these two parameters. During the surgery, the adjusted osteotomy guide was placed to the surface of bone closely and the guide pins were drilled into the bone through the guide holes. The position of the guide pins was confirmed under fluoroscopy. The osteotomy was finished under guide of pins and fixed with Tomofix plate (Synthes). The times and duration of placement of the guide pins, the times of X-ray examination, the planned and actual thickness of the osteotomy wedge, the top and bottom area of the osteotomy wedge, the posterior distal femoral angle(PDFA), the correction of the weight line, and the American Knee Society Score(AKSS) and Tegner scores were collected and compared by paired t test or Kruskal-Wallis non-parametric test. Healing time after osteotomy and complications were recorded. Results: The guide pins were successfully placed once in 10 knees, adjusted once in 5 knees and twice in 2 knees. The time spent in placing all the 6 pins was 82.4 seconds (range: 51 to 125 seconds), and the times of X-ray examination was 1.5 times (range: 1 to 5 times). The top and bottom areas of the osteotomy wedge were (5.52±0.52)cm(2) and (5.36±0.49)cm(2). PDFA was (85.2±2.6)° preoperatively and (85.5±1.4)° postoperatively (t=-0.401, P>0.05). The thickness of the osteotomy was (11.3±1.9)mm according to the preoperative plan, and the actual thickness was (8.1±1.7)mm. All the patients were followed up for 6 months after surgery and AKSS and Tegner scores improved significantly (all P<0.05). The correction of the weight lines was within the ideal range. Fractures of the hinge point occurred in 3 knees. All of the osseous healing without complications. Conclusion: The new osteotomy guide helps to place the guide pins rapidly and precisely according to the preoperative planning, which should be widely used in clinical applications with promising outcomes.

[Association between tooth missing and non-alcoholic fatty liver disease].

Objective: To evaluate the association between the number of teeth missed and the prevalence of non-alcoholic fatty liver disease (NAFLD) in adults. Methods: A cross-sectional study was carried out in 26 983 adults from Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. The number of teeth missed (excluding third molars) was recorded and classified into four categories: 0, 1-, 3- and ≥6. NAFLD was diagnosed by at least two liver ultrasonography examinations. Adjusted multivariable logistic regression analysis was used to access the association between the number of missed teeth and NAFLD in adults. Results: The overall prevalence of NAFLD was 7 270 and the number of the subjects with at least one tooth missed was 9 667. The multivariable-adjusted ORs (95%CI) of NAFLD across the categories of tooth missing (0, 1-, 3- and ≥6) were as follows: 1.00, 1.04 (0.93-1.15), 1.08 (0.93-1.26) and 1.38 (1.09-1.76) (trend test P=0.030) in males; 1.00, 0.96 (0.82-1.12), 1.11 (0.91-1.35) and 1.22 (0.90-1.64) (trend test P=0.450) in females. Conclusion: The number of missed teeth was positively associated with a higher prevalence rate of NAFLD in males with over 6 teeth missed, but not in females.

Systematic analysis of copy-number variations associated with early pregnancy loss.

OBJECTIVES: Embryonic numerical and structural chromosomal abnormalities are the most common cause of early pregnancy loss. However, the role of submicroscopic copy-number variations (CNVs) in early pregnancy loss is unclear, and little is known about the critical regions and candidate genes for miscarriage, because of the large size of structural chromosomal abnormalities. The aim of this study was to identify potential miscarriage-associated submicroscopic CNVs and critical regions of large CNVs as well as candidate genes for miscarriage. METHODS: Over a 5-year period, 5180 fresh miscarriage specimens were investigated using quantitative fluorescent polymerase chain reaction/CNV sequencing or chromosomal microarray analysis. Statistically significant submicroscopic CNVs were identified by comparing the frequency of recurrent submicroscopic CNVs between cases and a published control cohort. Furthermore, genes within critical regions of miscarriage-associated CNVs were prioritized by integrating the Residual Variation Intolerance Score and the human gene expression dataset for identification of potential miscarriage candidate genes. RESULTS: Results without significant maternal-cell contamination were obtained in 5003 of the 5180 (96.6%) cases. Clinically significant chromosomal abnormalities were identified in 59.1% (2955/5003) of these cases. Three recurrent submicroscopic CNVs (microdeletions in 22q11.21, 2q37.3 and 9p24.3p24.2) were significantly more frequent in miscarriage cases, and were considered to be associated with miscarriage. Moreover, 44 critical regions of large CNVs were observed, including 14 deletions and 30 duplications. There were 309 genes identified as potential miscarriage candidate genes through gene-prioritization analysis. CONCLUSIONS: We identified potential miscarriage candidate CNVs and genes. These data demonstrate the importance of CNVs in the etiology of miscarriage and highlight the importance of ongoing analysis of CNVs in the study of miscarriage. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Handwashing sinks as the source of transmission of ST16 carbapenem-resistant Klebsiella pneumoniae, an international high-risk clone, in an intensive care unit.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates (carrying the carbapenemase gene blaNDM-5) of sequence type 16 caused hospital-acquired bloodstream infection or gut colonization in two patients in an intensive care unit (ICU). It was hypothesized that handwashing sinks were the source, and all handwashing sinks in the ICU were sampled. Whole-genome sequencing and analysis revealed that one sink was the source of CRKP colonization/infection in both patients, instead of direct transmission of a common clone between the patients. This study highlights handwashing sinks as an important source of multi-drug-resistant organisms. Sink management, including prohibition of disposal of body fluids and daily disinfection with chlorine, curbed the transmission.

Supra-auricular and post-auricular resection of pre-auricular and post-auricular sinuses.

OBJECTIVE: This study aimed to classify the pre-auricular sinus before performing radical dissection, so as to achieve optimal aesthetic results. METHODS: The recent five-year clinical data of 53 patients with a congenital pre-auricular sinus and infection treated in the hospital were reviewed. According to the sinus course, pre-auricular and post-auricular types were defined, and regional dissection was performed using the modified supra-auricular or post-auricular approach. RESULTS: All patients achieved primary intention healing of the incision, and were followed up for six months to five years. No recurrence was found, and the incision scar was completely concealed. CONCLUSION: Surgical approaches for regional dissection might be adopted based on the different types of pre-auricular sinuses, and further radical dissection might be performed to achieve optimal aesthetic results.

[Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma].

OBJECTIVE: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. METHODS: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. RESULTS: (1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. CONCLUSION: Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

Screening and analysis on the differentially expression genes between diploid and autotetraploid watermelon by using of digital gene expression profile / Triagem e análise da expressão diferencial dos genes entre melancia diplóide e autotetraplóide através do perfil de expressão gênica digital

Abstract Synthetic polyploids are key breeding materials for watermelon. Compared with diploid watermelon, the tetraploid watermelon often exhibit wide phenotypic differences and differential gene expression. Digital gene expression (DGE) profile technique was performed in this study to present gene expression patterns in an autotetraploid and its progenitor diploid watermelon, and deferentially expressed genes (DEGs) related to the abiotic and biotic stress were also addressed. Altogether, 4,985 DEGs were obtained in the autotetraploid against its progenitor diploid, and 66.02% DEGs is up-regulated. GO analysis shows that these DEGs mainly distributed in 'metabolic process', 'cell' and 'catalytic activity'. KEGG analysis revealed that these DEGs mainly cover 'metabolic pathways', 'secondary metabolites' and 'ribosome'. Moreover, 134 tolerance related DEGs were identified which cover osmotic adjustment substance, protective enzymes/protein, signaling proteins and pathogenesis-related proteins. This study present the differential expression of stress related genes and global gene expression patterns at background level in autotetraploid watermelons. These new evidences could supplement the molecular theoretical basis for the better resistance after the genome doubling in the gourd family.

Resumo Poliploides sintéticos são materias fundamentais para melhoramento genético da melancia. Comparativamente ao seu homólogo diploide, a melancia tetraploide apresenta amplas diferenças genotípica e fenotípica e diferença de expressão gênica. A expressão gênica digital ou DGE (digital gene expression) foi utilizada neste estudo para representar o perfil de expressão gênica da melancia autotetraploide e seu progenitor diploide e a expressão diferencial de genes relacionados ao estresse biótico e abiótico. Os resultados mostraram que 4.985 DEGs foram observados no organismo autotetraploide, sendo que, deste total, 66.02%foram supra-regulados. A análise de ontologia gênica (GO) mostrou que estes DEGs estão relacionados principalmente com processos metabólicas, célula e atividade catalítica, abrangendo de acordo com a análise de genes e genoma (KEGG) rotas metabólicas, metabolismo secundário e ribossomos. Além disso, 134 genes de defesa foram identificados, abrangendo substâncias de ajuste osmótico, enzimas/proteínas de proteção, proteínas sinalizadoras e proteínas relacionadas à patogênese. Este estudo mostrou a expressão diferencial de genes relacionados ao estresse e o perfil global de expressão gênica de melancia autotetraploide, estes resultados podem complementar, a nível molecular, o entendimento do fator resistência após a duplicação do genoma em cucurbitáceas.

Screening and analysis on the differentially expression genes between diploid and autotetraploid watermelon by using of digital gene expression profile.

Synthetic polyploids are key breeding materials for watermelon. Compared with diploid watermelon, the tetraploid watermelon often exhibit wide phenotypic differences and differential gene expression. Digital gene expression (DGE) profile technique was performed in this study to present gene expression patterns in an autotetraploid and its progenitor diploid watermelon, and deferentially expressed genes (DEGs) related to the abiotic and biotic stress were also addressed. Altogether, 4,985 DEGs were obtained in the autotetraploid against its progenitor diploid, and 66.02% DEGs is up-regulated. GO analysis shows that these DEGs mainly distributed in 'metabolic process', 'cell' and 'catalytic activity'. KEGG analysis revealed that these DEGs mainly cover 'metabolic pathways', 'secondary metabolites' and 'ribosome'. Moreover, 134 tolerance related DEGs were identified which cover osmotic adjustment substance, protective enzymes/protein, signaling proteins and pathogenesis-related proteins. This study present the differential expression of stress related genes and global gene expression patterns at background level in autotetraploid watermelons. These new evidences could supplement the molecular theoretical basis for the better resistance after the genome doubling in the gourd family.

Clinical application of targeted next-generation sequencing in fetuses with congenital heart defect.

OBJECTIVES: To assess the value of targeted next-generation sequencing (NGS) in prenatal diagnosis of congenital heart defects (CHD) and to investigate the genetic etiology of prenatal CHD. METHODS: Forty-four fetuses with CHD, normal molecular karyotype and negative chromosomal microarray results underwent targeted NGS. Fetal genomic DNA was extracted directly from amniotic fluid cells in each prenatal case. A customized targeted-NGS panel of 77 CHD-associated genes was designed to detect variants in the coding regions and the splicing sites of these genes. The detected variants were classified as pathogenic, likely pathogenic, of uncertain significance, likely benign or benign, following the guidelines recommended by the American College of Medical Genetics and Genomics. RESULTS: The detection rates of targeted NGS for pathogenic and likely pathogenic variations were 13.6% (6/44) and 2.3% (1/44), respectively. The turnaround time of the test was 3 weeks. The six pathogenic variations were identified on the genes CHD7 (CHARGE syndrome), CITED2 (tetralogy of Fallot, ventricular septal defect and atrial septal defect), ZFPM2 (tetralogy of Fallot), MYH6 (atrial septal defect, familial isolated dilated cardiomyopathy) and, in two cases, KMT2D (Kabuki syndrome). The likely pathogenic variation was detected on JAG1, which is associated with tetralogy of Fallot and Alagille syndrome. Sanger sequencing in the fetuses and their parents indicated that all seven mutations were de novo. Variations of uncertain significance were detected in 79.5% of cases. CONCLUSIONS: Targeted NGS in fetuses with isolated and non-isolated CHD achieved a high diagnostic yield in our cohort, with an acceptable turnaround time for the prenatal setting. Our results have important implications for clinical management and genetic counseling. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Screening and analysis on the differentially expression genes between diploid and autotetraploid watermelon by using of digital gene expression profile

Abstract Synthetic polyploids are key breeding materials for watermelon. Compared with diploid watermelon, the tetraploid watermelon often exhibit wide phenotypic differences and differential gene expression. Digital gene expression (DGE) profile technique was performed in this study to present gene expression patterns in an autotetraploid and its progenitor diploid watermelon, and deferentially expressed genes (DEGs) related to the abiotic and biotic stress were also addressed. Altogether, 4,985 DEGs were obtained in the autotetraploid against its progenitor diploid, and 66.02% DEGs is up-regulated. GO analysis shows that these DEGs mainly distributed in metabolic process, cell and catalytic activity. KEGG analysis revealed that these DEGs mainly cover metabolic pathways, secondary metabolites and ribosome. Moreover, 134 tolerance related DEGs were identified which cover osmotic adjustment substance, protective enzymes/protein, signaling proteins and pathogenesis-related proteins. This study present the differential expression of stress related genes and global gene expression patterns at background level in autotetraploid watermelons. These new evidences could supplement the molecular theoretical basis for the better resistance after the genome doubling in the gourd family.

Resumo Poliploides sintéticos são materias fundamentais para melhoramento genético da melancia. Comparativamente ao seu homólogo diploide, a melancia tetraploide apresenta amplas diferenças genotípica e fenotípica e diferença de expressão gênica. A expressão gênica digital ou DGE (digital gene expression) foi utilizada neste estudo para representar o perfil de expressão gênica da melancia autotetraploide e seu progenitor diploide e a expressão diferencial de genes relacionados ao estresse biótico e abiótico. Os resultados mostraram que 4.985 DEGs foram observados no organismo autotetraploide, sendo que, deste total, 66.02%foram supra-regulados. A análise de ontologia gênica (GO) mostrou que estes DEGs estão relacionados principalmente com processos metabólicas, célula e atividade catalítica, abrangendo de acordo com a análise de genes e genoma (KEGG) rotas metabólicas, metabolismo secundário e ribossomos. Além disso, 134 genes de defesa foram identificados, abrangendo substâncias de ajuste osmótico, enzimas/proteínas de proteção, proteínas sinalizadoras e proteínas relacionadas à patogênese. Este estudo mostrou a expressão diferencial de genes relacionados ao estresse e o perfil global de expressão gênica de melancia autotetraploide, estes resultados podem complementar, a nível molecular, o entendimento do fator resistência após a duplicação do genoma em cucurbitáceas.