[Analysis of etiology and complications in children with stage 5 chronic kidney disease].

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.

[Clinical characteristics of convalescent children infected with SARS-CoV-2 Omicron variant in Tianjin].

Objective: To analyze the clinical characteristics of SARS-CoV-2 Omicron variant infected children in convalescence in Tianjin. Methods: A total of 104 pediatric patients infected by SARS-CoV-2 Omicron variant Tianjin First Central Hospital (designated hospital for SARS-CoV-2 infection in Tianjin) for convalescent treatment from January 22nd, 2022 to February 24th were included for a retrospective study.Clinical data including clinical typing, SARS-CoV-2 IgG and IgM test and 2019-nCoV nucleic acid test were collected.The cases were divided into 2-dose group and zero-dose group based on the doses of inactivated SARS-CoV-2 vaccine. The children were divided into repositive group and negative group, according to the nucleic acid test during hospitalization. Chi-square test was used for the comparison between the groups. Results: The age of these 104 children was 10.0 (0.3, 14.0) years on admission, 53 children were males and 51 were females, 92 cases (88.5%) had mild symptoms, 12 cases (11.5%) had common symptoms.The age and SARS-CoV-2 IgG level of zero-dose group was lower (2.0 (0.3, 10.2) vs. 10.0 (3.2, 14.0) years, 10 (2, 17) vs. 193 (157, 215), χ²=-5.57, Z=-48.76,both P<0.001) than that of 2-dose group. The zero-dose group had a high rate of transmission among family members and a high level of SARS-CoV-2 IgM level (13/14 vs. 62.2% (56/90), 0.4 (0.2, 0.8) vs. 0.4 (0.2, 1.1),χ²=5.09, Z=-48.95, both P<0.05) than the 2-dose group. Repositive group had a high rate of underlying diseases and SARS-CoV-2 IgM level was higher (2/13) vs. 1.1% (1/91), (0.6 (0.2, 1.0) vs. 0.3 (0.2, 0.7), χ²=8.29, Z=2.70, both P<0.05) than negative group. The SARS-CoV-2 IgG level of repositive group was lower than that of negative group (160 (78, 197) vs. 213 (186, 231), χ²=-3.20, P<0.05). Conclusions: Children infected with SARS-CoV-2 Omicron variant in Tianjin were mainly transmitted by family members, and most of them had mild symptoms. Two-dose group had higher IgG levels and lower IgM levels than zero-dose group.The probability of SARS-CoV-2 nucleic acid test repositivity increased in children with underlying diseases and lower IgG levels.

[Genotype-phenotype analysis and prognosis in children with primary distal renal tubular acidosis].

Objective: The purpose of this study was to investigate the relationship between genotypes and clinical phenotypes of primary distal renal tubular acidosis (dRTA) in children. Methods: Clinical information, genetic testing information and follow-up data (until March 2021) of children with dRTA from Children's Hospital of Chongqing Medical University (from January 2010 to December 2020) were analyzed retrospectively. According to different pathogenic genes, patients were divided into SLC4A1 gene and ATP6V0A4+ATP6V1B1 gene groups. Age at onset, clinical manifestations and laboratory findings were compared. Self-comparisons of height standard deviation score (HtSDS), weight standard deviation score (WtSDS), blood pH and serum potassium before and after treatment were tested. T-test, Fisher's exact test and rank sum test were used to analyze among groups. Results: Among 27 children with dRTA (16 boys and 11 girls), the age of onset was 33.4 (10.0, 36.0) months.There were 22 patients (81%) with SLC4A1 gene variation, 3 patients (11%) with ATP6V1B1 gene variation and 2 patients (8%) with ATP6V0A4 gene variation. Totally 22 patients (81%) with renal calcium deposition, 19 patients (70%) hypokalemia, 18 patients (67%) short stature, 16 patients (59%) malnutrition, 16 patients (59%) rickets, and 15 patients (56%) polydipsia and polyuria. Noteworthily, the genotyping results indicated that the age at onset in SLC4A1 gene group was older than that in ATP6V0A4+ATP6V1B1 gene group, with a statistically significant difference (27.3 (12.0, 36.0) vs. 8.2 (2.5, 15.0) months, H=6.33, P=0.012). However, there were no significant differences in clinical manifestations or laboratory test results (all P>0.05). Furthermore, the course of disease was 3.9 (1.3, 6.0) years and the follow-up period was 3.1 (1.0, 4.5) years in 27 patients. In addition, there were no significant differences in recovery rate of clinical manifestations and last laboratory findings between SLC4A1 gene group and ATP6V0A4+ATP6V1B1 gene group (all P>0.05). HtSDS and WtSDS of those patients significantly increased after treatment (-3.2±1.9 vs. -2.1±1.1, -2.5±1.5 vs. 0±1.9, t=-2.94, -5.44, both P<0.01). Serum K+ and blood pH were restored eventually ((3.2±0.5) vs. (4.0±0.5) mmol/L, 7.27±0.07 vs. 7.37±0.07, t=-4.92, -5.25, both P<0.01). Totally 14 patients had normalized serum potassium, 12 patients had normalized blood pH, but only 4 patients had normalized serum bicarbonate concentration and normal base excess. Conclusions: The age of onset of patients who had SLC4A1 gene mutation was older than that of patients with ATP6V0A4 gene and ATP6V1B1 gene mutations. However, there was no obvious correlation between the condition and prognosis of the dRTA patients and pathogenic genes. Early diagnosis, early treatment, regular follow-up and timely adjustment of the dosage of medication can significantly improve the prognosis of dRTA in children. Serum bicarbonate concentration and actual base excess might not be the necessory indicators to assess clinical recovery.

Study of the Structure and Properties of ZnS Utilized in a Fluorescence Biosensor.

ZnS materials have been widely used in fluorescence biosensors to characterize different types of stem cells due to their excellent fluorescence effect. In this study, ZnS was prepared by vulcanizing nano-Zn particles synthesized using a DC arc plasma. The composition and structure of the ZnS materials were studied by X-ray diffraction (XRD), and their functional group information and optical properties were investigated by using IR spectrophotometry and UV-vis spectrophotometry. It has been found that the synthesized materials consist of Zn, cubic ZnS, and hexagonal ZnS according to the vulcanization parameters. Crystalline ZnS was gradually transformed from a cubic to a hexagonal structure, and the cycling properties first increase, then decrease with increasing sulfurization temperature. There is an optimal curing temperature giving the best cycling performance and specific capacity: the material sulfurized thereat mainly consists of cubic ß-ZnS phase with a small quantity of Zn and hexagonal α-ZnS. The cubic phase ZnS has better conductivity than hexagonal ZnS, as evinced by electrochemical impedance spectroscopy (EIS). The ZnS (as prepared) shows board absorption, which can be used in fluorescence biosensors in cell imaging systems.

[Mechanism of scavenger receptor-A in high glucose-induced inflammatory injury of mesangial cells].

Objective: To investigate the effect of high glucose on scavenger receptor-A (SR-A) in human glomerular mesangial cells (HMC) and explore the mechanism of inflammatory injury mediated by SR-A in HMC cultured in high-glucose medium. Methods: According to the concentration of D-glucose in culture medium, HMC were divided into normal glucose group (5.5 mmol/L) and high glucose group (30 mmol/L), with mannitol group as hypertonic control. High glucose group was transfected with SR-A small interfering RNA (siSR-A) and the transfection control (siNC) group were set up. Western blotting technology was used to detect the levels of SR-A, NOD-like receptor family pyrin domain-containing 3 (NLRP3), interleukin-1ß (IL-1ß) protein. Immunofluorescent staining was applied to measure the SR-A in HMC. The mRNA of NLRP3, Caspase-1, IL-1ß, FN, ColⅣ, α-SMA and GRP78 were detected by real-time quantitative PCR. The relative activity of Caspase-1 was detected by enzyme method and the concentration of IL-1ß in culture medium was detected by enzyme linked immunosorbent assay. Flow cytometry was used to measure the cell cycles of HMC. One-way ANOVA and SNK-q test were used for statistical analysis. Results: The protein level of SR-A in high glucose group was higher than that in normal glucose group and mannitol group (1.23±0.21 vs. 0.68±0.10, 1.23±0.21 vs. 0.78±0.13, all P<0.05). In addition, mean fluorescence intensity of SR-A, protein levels of NLRP3 and IL-1ß, mRNA of NLRP3, Caspase-1 and IL-1ß, relative activity of Caspase-1 as well as the concentration of IL-1ß in high glucose group were all significantly higher than those in normal glucose group and mannitol group (all P<0.05).After transfection induced silencing, SR-A protein in high glucose siNC group was higher than that in high glucose siSR-A group and normal glucose siNC group (1.23±0.10 vs. 0.20±0.01, 1.23±0.10 vs. 0.87±0.01, all P<0.01). In high glucose siNC group, the NLRP3, IL-1ß proteins, the NLRP3, Caspase-1 and IL-1ß mRNA, all of the mRNA levels of FN, ColⅣ, α-SMA, GRP78 and the proportion of DNA synthesis phase were all higher than those in high glucose siSR-A group and normal glucose siNC group (all P<0.05). Conclusion: High glucose can promote abnormal cell proliferation, increase mesangial matrix production and enhance oxidative stress response through upregulating SR-A expression, and ultimately aggravate cellular inflammatory damage in HMC, which may be associated with NLRP3-Caspase-1-IL-1ß pathway regulated by SR-A expression.

[Laboratory investigation for one gastroenteritis outbreak caused by Campylobacter jejuni].

Objective: To understand the etiological characteristics of an acute gastroenteritis outbreak. Methods: Real-time polymerase chain reaction (PCR) and bacteria cultures were performed for the samples, including stool samples from patients and cooks, environmental swabs, raw food material (chicken meat), collected during the outbreak. Pulsed-field gel electrophoresis, antibiotics susceptibility test and whole-genome sequencing were performed for the Campylobacter jejuni isolates. Results: Four stool samples from patients were positive for Campylobacter jejuni by real-time PCR, in which 1 Campylobacter jejuni strain was isolated from a case who had no antibiotic treatment. Twelve Campylobacter jejuni and 7 Campylobacter coli isolates were obtained from 4 raw chicken meat samples. The Campylobacter jejuni strain isolated from the case was resistant to nalidixic acid, ciprofloxacin, chloramphenicol, florfenicol and tetracycline. The MLST analysis with the whole-genome sequences confirmed that the Campylobacter jejuni isolate from the case belonged to ST10075. Antimicrobial resistance genes cmeABCR, tetO/M and blaOXA-61 were found in the genome of the isolate from the patient by the whole-genome sequencing. No mutation in 23S rRNA was found and the C257T mutation in gyrA was identified in this isolate. Conclusion: Laboratory analysis indicated that Campylobacter jejuni infection might be the major cause of this gastroenteritis outbreak.

[Meta-analysis of clinical effects of microskin grafting and Meek microskin grafting in repairing extensively deep burn wounds].

Objective: To systematically evaluate the clinical effects of microskin grafting and Meek microskin grafting in repairing extensively deep burn wounds using meta-analysis. Methods: Foreign language databases including PubMed and Cochrane Library were searched with the terms of " Meek micrografting, burn" , and Chinese databases including Chinese Journal Full-Text Database, Chinese Biomedical Database, VIP database, and Wanfang Data were searched with the terms in Chinese version of ", Meek," to retrieve the publicly published randomized controlled trials on the microskin grafting and Meek microskin grafting in repairing extensively deep burn wounds from the establishment of each database to March 20, 2019. The outcome indexes included the survival rate of skin graft, primary healing rate, operation time, and surgical treatment cost after the first operation, as well as the wound healing time and length of hospital stay. RevMan 5.3 and Stata 14.0 statistical software were used to conduct a meta-analysis of eligible studies. Results: A total of 821 patients with extensively deep burns were included in 15 studies, including 410 patients in microskin group who received microskin grafting and 411 patients in Meek microskin group who received Meek microskin grafting. The bias risks of the 15 studies included were uncertain. Compared with those of microskin group, the survival rate of skin graft and primary healing rate of patients in Meek microskin group were significantly increased, with relative risks of 0.76 and 0.66 (95% confidence interval=0.66-0.88, 0.50-0.88, P<0.01), the surgical treatment cost was significantly reduced, with a standardized mean difference of 3.19 (95% confidence interval=1.36-5.01, P<0.01), and the operation time, wound healing time, and length of hospital stay were significantly shortened, with standardized mean differences of 6.05, 2.39, and 2.35 (95% confidence interval=3.66-8.44, 1.43-3.35, 2.03-2.68, P<0.01). Subgroup analysis showed that microskin grafting combined with allogenic skin graft might be a heterogeneous source of operation time. Sensitivity analysis showed that the combined effect size was stable in the operation time, surgical treatment cost, and wound healing time. There was no publication bias in the survival rate of skin graft, operation time, wound healing time, and length of hospital stay (P>0.05), while the primary healing rate and surgical treatment cost had publication bias (P<0.01). Conclusions: Compared with microskin grafting, Meek microskin grafting improves the rates of skin graft survival and primary healing, shortens operation time, wound healing time, and length of hospital stay, and reduces the treatment cost in treating extensively deep burn wounds.

[Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region].

Objective: To understand the clinical characteristics, change of liver function, influencing factors and prognosis in hospitalized patients with coronavirus disease-19 (COVID-19) combined with liver injury. Methods: The general conditions, biochemical indicators of liver, blood clotting mechanism, routine blood test, UGT1A1 * 28 gene polymorphism and other data of 40 cases with COVID-19 admitted to the isolation ward of Tangdu Hospital were retrospectively analyzed. The clinical characteristics, influencing factors and prognosis of liver injury in patients with liver injury group and those with normal liver function group were compared. The mean of two samples in univariate analysis was compared by t-test and analysis of variance. The counting data was measured by χ(2) tests. The non-normal distribution measurement data were described by the median, and the non-parametric test was used. Statistically significant influencing factors were used as the independent variables in univariate analysis. Multiple logistic regression analysis was used to analyze the main influencing factors of liver injury. Results: Of the 40 cases, 25 were male (62.5%) and 15 were female (37.5%), aged 22 to 83 (53.87 ± 15.84) years. Liver injury was occurred in 22 cases (55%) during the course of the disease. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level was initially increased (4.4 to 3.5 times of the normal value) along with decrease of albumin in the second week, and the difference was statistically significant (P < 0.001). Ten cases (43.5%) had highest abnormal total blood bilirubin (54.1 µmol/ L). There was no correlation between the increase in transaminase and the increase in total blood bilirubin (R = -0.006, P = 0.972). Three cases had prothrombin activity (PTA) of ≤50%, 10 cases had elevated FDP, and 13 cases had elevated D-dimer, all of whom were severe or critically ill. Liver function injury was more likely to occur in patients who used many types of drugs and large amounts of hormones (P = 0.002, P = 0.031), and there was no correlation with the TA6TA7 mutation in the UGT1A1 * 28 gene locus. Multiple regression analysis showed that the occurrence of liver injury was only related to critical illness. The liver function of all patients had recovered within one week after conventional liver protection treatment. Conclusion: COVID-19 combined with liver function injury may be due to the slight elevation of transaminase, mostly around the second week of the disease course. Severe patients have a higher proportion of liver injury, and critical type is an independent risk factor for liver injury.

MiR-19 enhances pancreatic cancer progression by targeting PTEN through PI3K/AKT signaling pathway.

OBJECTIVE: Abnormal expression of micro ribonucleic acids (miRNAs) has become an important marker of cancer. However, the exact molecular mechanisms of miRNAs were not very clear. Here, we decided to investigate the miR-19 effect and molecular mechanism on pancreatic cancer, which was blank until now. PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was applied for testing miR-19 and gene of phosphate and tensin homolog deleted on chromosome ten (PTEN) expression. Western blot was used for detecting the protein expression. Methyl thiazolyl tetrazolium (MTT) assay and transwell assay were carried out to measure cell proliferation, invasion, and migration. RESULTS: We showed that miR-19 expression was increased in cancerous tissues and was associated with the survival of patients, tumor node metastasis (TNM) stage, tumor size, and lymph node metastasis. MiR-19 mimic enhanced cell proliferation, invasion, and migration, while suppressing miR-19 cell progression was suppressed. With the help of TargetScanHuman and luciferase reporter assay, we verified PTEN as a specific target of miR-19. Moreover, PTEN expression was reduced by miR-19 mimic and was increased by miR-19 inhibitor. We next found that PTEN was elevated in cancerous tissues and its expression was negatively correlated with miR-19 expression. Furthermore, miR-19 regulated cell progression via activating phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. CONCLUSIONS: We demonstrated that miR-19 facilitated cell progression through modulating PI3K/AKT signaling pathway by targeting PTEN, which provided a potential therapeutic target for pancreatic cancer patients.

[Long-term efficacy analysis of laparoscopic-assisted anorectoplasty for high and middle imperforate anus].

Objective: To explore the long-term efficacy of laparoscopic-assisted anorectoplasty and conventional anorectoplasty in the treatment of children with high and middle anal atresia. Methods: A retrospective cohort study was used. Inclusion criteria: (1) children with high and middle anal atresia; (2) complicated with rectourethral or rectovesical fistula; (3) complete follow-up data. Exclusion criteria: (1) complicated with 21-trisomy; (2) cerebral palsy and other mentaldisabilities; (3) Currarino syndrome; (4) FG syndrome. Clinical data of 88 patients with middle and high anal atresia, who complicated with rectourethral fistula or rectovesical fistula, and underwent anoplasty at Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University from January 2009 to June 2014 were enrolled in the study and analyzed. There were 24 cases with middle atresia and 64 cases with high atresia. All the cases were divided into 2 groups based on the operative method: laparoscopic group (laparoscopic-assisted anorectoplasty, 49 cases), pena group (posterior sagittal anorectoplasty, 39 cases). The demographic features of two groups were comparable. There were no statistically significant differences in gender, age, body mass, classification of anomaly types and sacral ratio (all P>0.05). Student t test and Chi square tests were used to compare the surgical conditions (operative time, postoperative hospital stay and complications), anal function (Kelly score), constipation (Krickenbeck constipation score) and anorectal pressure. Results: Children of both groups all completed operation ssuccessfully. There were no statistically significant differences between laparoscopic group and pena group in the operative time [(120±31) minutes vs. (112±23) minutes, t=1.343, P=0.091] and postoperative hospital stay [(7.1±2.3) days vs. (10.7±3.3) days, t=6.021, P=1.000]. Complications were more common in the pena group [16.3% (8/49) vs. 35.9% (14/39), χ(2)=4.436, P=0.035]. The main complications in laparoscopic group were anal prolapse (8.2%, 4/49) and anal stenosis (6.2%, 3/49), while in pena group were anal stenosis (12.8%, 5/39) and perioperative perianal skin erosion (10.3%, 4/39). As for the anal function, the degree of feces, defecation control and sphincter contractility, the single scoring differences of Kelly scoring system were not statistically significant between the two groups, but the proportion of good function in the laparoscopic group was higher than that in the pena group [67.3% (8/49) vs. 38.5% (15/39), χ(2)=7.308, P=0.007]. Constipation occurred in 6 (12.2%) patients in the laparoscopic group, of whom 5 were improved by diet regulation and 1 required laxatives, while 9 (23.1%) patients developed constipation in the pena group, of whom 4 were improved by diet regulation and 5 required long-term laxatives. The difference of constipation ratio was not statistically significant (χ(2)=1.802, P=0.180). There were no cases of Krickenbeck constipation grade 3. Compared to the pena group, the laparoscopic group had higher anal resting pressure [(33.35±9.69) mmHg vs. (27.68±10.74) mmHg, t=2.599, P=0.011], higher dilating pressure [(9.00±5.61) mmHg vs.(6.51±3.24) mmHg, t=2.462, P=0.016], higher maximal squeeze pressure [(65.80±17.23) mmHg vs. (56.74±18.93) mmHg, t=2.389, P=0.019] and longer maximal contraction time [(21.16±5.02) seconds vs. (18.44±7.24) seconds, t=2.079, P=0.041]. The rectal resting pressure [(5.36±3.00) mmHg vs. (4.61±3.93) mmHg, t=1.015, P=0.312] was not statistically significantly different. Conclusions: Compared with posterior sagittal anorectoplasty, laparoscopic-assisted anorectoplasty in the treatment of high and middle anal atresia has better long-term efficacy with less perioperative complications.

Whole solid tumour volume histogram analysis of the apparent diffusion coefficient for differentiating high-grade from low-grade serous ovarian carcinoma: correlation with Ki-67 proliferation status.

AIM: To investigate whether apparent diffusion coefficient (ADC) histogram parameters based on whole solid tumour volume could differentiate high-grade (HGSOC) from low-grade serous ovarian carcinoma (LGSOC) and to correlate those parameters with the Ki-67 proliferation index. MATERIALS AND METHODS: One hundred and seven patients with HGSOCs and 19 patients with LGSOCs confirmed at surgery and histology who underwent conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) were analysed retrospectively. ADC histogram parameters (including the mean, standard deviation [SD], 10th, 25th, 50th, 75th, and 90th percentiles, kurtosis, and skewness) were obtained using the whole solid tumour volume region of interest (ROI). The Mann-Whitney U test, Pearson's chi-square test, Fisher's exact test, kappa test, Spearman's correlation, and receiver operating characteristic (ROC) curves were used for statistical analyses. RESULTS: For ADC histogram parameters, the mean (p<0.001), SD (p=0.003), and all percentiles (10th, 25th, 50th, 75th, and 90th percentile; all p<0.001) were significantly lower in HGSOC than in LGSOC, and the area under the ROC curve (AUC) was 0.717-0.807. Skewness was significantly higher in HGSOC than in LGSOC (p<0.001, AUC = 0.773); however, kurtosis was not significantly different between HGSOC and LGSOC (p=0.140). The 25th and 75th percentiles, SD and 10th percentile, and 75th percentile showed the highest sensitivity of 91.6%, specificity of 79.0%, and accuracy of 88.1%, respectively. All histogram parameters (except for kurtosis) were poorly correlated with the Ki-67 index (|r| = 0.191-0.274, p<0.05). CONCLUSION: ADC histogram parameters based on whole solid tumour volume can be helpful for differentiating between HGSOC and LGSOC.

[Quantitative study on the development of fetal ventricles and cisterna magna in second and third trimesters with MRI].

Objective: To analyze the changes of growth and development of normal fetal ventricles and cisterna magna with gestational age(GA) and the correlation with fetal gender in the second and third trimester,and establish the MR prenatal diagnosis reference standards. Methods: A total of 633 fetuses (mean GA (27.0±4.1) weeks (18.9-40.6 weeks))without central nervous system abnormalities were retrospectively collected from the Obstetrics and Gynecology Hospital of Fudan University from June 2012 to August 2017. The lateral ventricle trigonometric width (LVTW), third ventricle width (TVW), fourth ventricle width (FVW), anterior-posterior diameter of the fourth ventricle(APDFV), cavum septum pellucidum width (CSPW) and cisterna magna width (CMW) were obtained in the standard measure planes on MR image.The correlation between the biometrics and GA and the correlation between the biometrics and fetal gender were analyzed respectively, and the normal reference values of the biometrics were calculated. Spearman correlation analysis, Pearson correlation analysis,linear regression analysis, independent samples t-test and paired samples t-test were used for statistic analysis. Results: (1)Fetal LLVTW,RLVTW,TVW,CSPW and CMW in second and third trimesters were correlated with GA at medium and low levels(the correlation coefficient r were 0.311, 0.277, 0.207, 0.226, 0.295, respectively, all P<0.01). FVW and APDFV were statistically correlated with GA, and the linear regression equations were as follows: y=0.022×GA-0.043 (adjusted R(2)=0.642); y=0.018×GA-0.159 (adjusted R(2)=0.690). (2)Fetal LLVTW,RLVTW,FVW,APDFV and CSPW were not correlated with fetal gender in second and third trimesters(r=-0.078,-0.057,-0.087,-0.004 and 0.024, P=0.124,0.258,0.085,0.931 and 0.618, all P>0.05). TVW and CMW were statistically correlated with fetal gender(r=-0.310, -0.180, P=0.000, 0.006, all P<0.05). (3) The mean values of LLVTW and RLVTW were (0.71±0.13) cm and (0.68±0.13) cm, respectively, and significant difference was found between them(t=3.180, P=0.002). The mean value of CSPW was (0.59±0.15) cm. And the mean values of male and female fetuses for TVW and CMW were (0.17±0.05) cm, (0.16±0.06) cm and (0.68±0.15) cm, (0.58±0.15) cm, respectively. The corresponding prenatal MRI diagnostic criteria were as follows: LLVTW 1.1 cm, RLVTW 1.0 cm, CSPW 1.0 cm, TVW 0.3 cm, CMW (male 1.1 cm, female 1.0 cm). Conclusions: The normal fetal ventricles and cisterna magna are increased with the GA in the second and third trimesters. TVW and CMW are related to fetal gender. The establishment of normal reference values of fetal ventricles and cisterna magna based on GA and fetal gender are conducive to enhance the accuracy of MRI prenatal diagnosis.

A new delineation method research of the clinical target volume for pancreatic cancer adjuvant radiotherapy.

PURPOSE: The purpose of this work was to establish a map model of the local recurrence location after pancreatic cancer resection and to generate a new delineation method of clinical target volume, with the aim to effectively improve the adjuvant radiotherapeutic gain ratio. METHODS AND MATERIALS: The clinical and imaging data of 48 patients with resected pancreatic head cancer and pancreatic body cancer with local recurrences were collected. Local recurrences were all plotted with reference to the geometric centre of the local recurrent foci. Based on the coordinates of the local recurrences with respect to the celiac artery or the superior mesenteric artery, a three-dimensional local recurrence map model was established on the computed tomography image. The adjuvant radiation clinical target volumes encompassing 90% of all local failures and encompassing 90% of postoperative pancreatic head cancer local failures were created respectively. This new delineation method and RTOG 0848 protocol were applied in five simulated cases, then corresponding types of target volumes and plans were generated for comparison. RESULTS: The clinical target volume encompassing 90% of all local failures was generated by expanding the combined celiac artery and superior mesenteric artery contour by 1.4cm superior, 1.9cm inferior, 2.6cm left-lateral, 3.1cm right-lateral, 1.9cm anterior and 1.6cm posterior. The corresponding expansions of clinical target volume encompassing 90% of postoperative pancreatic head cancer local failures were 1.4cm, 1.4cm, 2.1cm, 3.1cm, 1.6cm and 2.0cm. The volumes of "new" target PTV-90_edited, PTV-90_H_edited, and the standard target PTV_edited were 217.64±58.67 cm3, 207.78±50.94 cm3 and 320.72±50.94 cm3 in simulated cases. Comparison showed that the "new" target volumes were much smaller than the standard volumes per RTOG 0848 protocol, and the dose received by organs at risk was also lower in the "new" plans. CONCLUSIONS: A majority of postoperative local recurrences in patients with pancreatic head and body cancer are contained within a smaller region surrounding the celiac artery and superior mesenteric artery. The "new" volumes targeting high risk local failures may allow dose escalation and enhanced local control while minimizing radiation-related toxicity.

MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.

OBJECTIVE: Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood. Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant. PATIENTS AND METHODS: Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines. Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines. Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p. Moreover, we showed that miRNA-485-5p regulated EC tumorigenesis by down-regulating OGT expression in vitro and in vivo. RESULTS: The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR. Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells. The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences. Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p. Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells. CONCLUSIONS: Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.

[Expression of type 1 and type 2 cytokines from serum of coal miners and the evaluation in surveillance of coal workers' pneumoconiosis at earlier stage].

Objectives: To explore the expression regulation of type 1 and type 2 (Th1 and Th2) cytokines from serum of coal miners and the evaluation in surveillance of coal workers' pneumoconiosis, 630 coal miners were studied. Methods: A total of 90 male patients diagnosed as coal workers' pneumoconiosis (CWP) in a institute for occupational health and 19 male workers newly diagnosed as CWP patients was chosen as CWP group with simple random sampling method from a coal mine group from January 2013 to December in 2015. 180 male coal miners with abnormal but not diagnosed as CWP were selected as CWP suspected group with simple random sampling methods, meanwhile 180 male coal miners with normal chest X-ray photograph was as dust-exposed group by 1∶1 matched as age. And 161 healthy males accepted pre-employed examination were selected as control group, CWP suspected group, dust-exposed group and control group called as non-CWP group. According to screening test and diagnosis test, the basic information and occupational history of all subjects were collected, and cytokines including IL-1ß, IL-8, IFN-γ, IL-6 and IL-10 of serum were detected. Receiver operator characteristic (ROC) curve was used to determine the optimal cutoff value of each cytokine. Area under curve (AUC), the validity and reliability were calculated and judged. Results: The average age of control group, dust-exposed group, CWP suspected group and CWP group were (27.4±5.0) , (43.4±10.7) , (48.2±6.2) , (64.7±7.0) years old, respectively. The median level of IL-1ß, IL-8, IFN-γ and IL-6 in cases group (1 638.30, 2 099.49, 815.18,140.32 pg/ml) were higher than that of non-cases group (1 445.57, 1 402.26, 736.38, 95.73 pg/ml) (P<0.05) . The level of IL-8 (1 503.99 pg/ml) in CWP suspected group was higher than that of control group (1 295.67 pg/ml) and dust-exposed group (1 376.94 pg/ml) , but the level of IL-10 (654.08 pg/ml) was lower than that of control group (596.64 pg/ml) . The ratio of IFN-γ/IL-6 ranged from 5 to 8, and the ratio in CWP group (5.87) was lower than that of non-CWP group (7.61) . The IL-6 and IL-8 among the subjects of dust-exposed group in terms of the age distribution of among had reached statistical significance. According to ROC, the cutoff value of IL-1ß, IL-6, IL-8, IL-10 and INF-γ reached 1 582.65, 116.53, 1 791.54, 581.08 and 792.69 pg/ml, respectively. The AUC was 0.668, 0.895, 0.859, 0.716 and 0.637, respectively. It was found that IL-6 and IL-8 could be used as biomarkers in detecting CWP, the sensitivity and specificity was 82.6% and 84.6%, 78.0% and 84.8%, respectively; Youden's index was 0.674 and 0.628 and the consistency rate was 84.3% and 83.7%, while Kappa value was 0.55 and 0.52. Conclusion: There was Type 1 and type 2 cytokine dysregulation in CWP patients. IL-6 and IL-8 can be used as effective biomarkers to forecast lung injury before X-ray changes.

[Application of chest CT scan in gestational trophoblastic neoplasia with lung metastasis].

Objective: To explore the role of CT scan for the diagnosis of lung metastasis in stage Ⅲ gestational trophoblastic neoplasia (GTN) . Methods: To figure out the role of CT scan for lung metastasis in GTN initial diagnosis, treatment and follow-up, 93 GTN patients with lung metastasis from January, 2015 to December, 2016 were retrospectively analyzed in Obstetrics and Gynecology Hospital of Fudan University. Results: (1) Among 93 GTN patients with lung metastasis, 70 patients with the International Federation of Gynecology and Obstetrics (FIGO) score ≤6 were defined as low risk GTN and 23 patients score score ≥7 were defined as high risk GTN. Forty nine patients had negative chest X-ray findings and 39 cases with pulmonary lesions were identified both by chest X-ray compared to CT scan. Five cases were excluded due to no consensus could make for the results of chest X-ray. The true positive rate of chest X-ray for lung metastasis were 41% (29/70) in low risk GTN and 43% (10/23) in high risk GTN patients without statistical difference (χ(2)=0.090, P=0.925) . For those patients with positive chest CT scan and negative chest X-ray finding, pulmonary lesions in 32 (65%, 32/49) cases were blocked by heart, chest wall or diaphragm in chest X-ray. Seventeen (35%,17/49) patients with lung lesions less than 5 mm had negative chest X-ray results due to the lower sensitivity compared to CT scan. (2) In 88 patients with stage Ⅲ, 78 patients had successful initial treatment, but 4 of them were recurrence in twelve months follow-up. Ten patients were chemotherapy resistance for the initial treatment. The initial chemotherapy remission rate in low risk GTN patients was higher than that in high risk ones (χ(2)=4.911, P=0.027) . In 49 cases with negative chest X-ray, there was no correlation with the rate of remission,chemotherapy resistance and recurrence in stage Ⅲ patients (P>0.05) . (3) For those patients who had poorly response to initial chemotherapy, the diameters of lesions in lung were unchanged or increased during the treatment, form (5.1±4.1) mm to (7.4±2.8) mm. The pulmonary lesions were continuously shrunk from (7.8±5.3) mm to (4.7±4.4) mm for those patients with complete and partial remission including the recurrent GTN patients (Z=-2.713, P=0.007) . Conclusions: Patients with GTN in stage Ⅲ have down staging if only use chest X-ray for imaging at the initial diagnosis. Chest CT scan is recommended for primary imaging evaluation of FIGO staging in qualified medical organization. For those patients with persistent abnormal serum hCG level and negative chest X-ray, chest CT scan is strongly recommended to identify the persist or resistant lung lesions and follow up.

[Management of T3 supraglottic carcinoma: a retrospective study].

Objective: To discuss the strategy of therapeutic management of T3 supraglottic carcinoma. Methods: A retrospective analysis of 459 patients with T3 supraglottic carcinoma treated in our hospital was performed. We evaluated the results of different managements, including surgery alone, preoperative radiotherapy, postoperative radiotherapy and radiotherapy alone. The extent of the lesion was also put into analysis. Statistical analysis of the overall survival (OS), cause-specific survival (CSS), local control (LC), regional control(RC), function-conservation (FC) were performed with the statistical package from SPSS. Results: In all patients, the rates of 5-year OS, CSS, LC, RC and FC were 64.2%, 71.2%, 87.8%, 78.8% and 64.5% respectively. The OS, LC and FC of the patients treated by surgery alone, preoperative radiotherapy and postoperative radiotherapy had no significant difference, and were remarkably better than that of patients treated by radiotherapy alone (P<0.001). In 412 patients treated by surgery, 300 patients received function-conservation laryngectomy. 209 patients (50.7%, 209/412) survived and maintained well-function of larynx for 5 years, which was significantly better than those in the radiotherapy alone group (27.7%, 13/47). The patients with the lesion invading the pre-epiglottic space but limited in supraglottic area had better OS (70.2%), LC (93.5%) and FC (85.1%). The rate of 5-year neck lymphatic metastasis was 56.2%(258/459), and the 5-year OS of patients with N0, N1, N2 and N3 stage were 76.0%, 66.2%, 50.5% and 13.0% respectively. Conclusions: Surgical treatment was the best therapeutic approach for T3 supraglottic laryngeal carcinoma. Most patients with T3 lesions are suitable for function-conservation laryngectomy. Surgical procedure was determined by tumor invaded location and extension. The combined therapy of surgery and radiotherapy had no significant advantage.

Mechanism of age-related changes of bone marrow mesenchymal stem cells in senile osteoporosis.

This study was carried out to explore the age-related changes of bone marrow mesenchymal stem cells (BMMSCs) in mice as well as the influence of autophagy on the age-related changes of BMMSCs. BMMSCs aging-associated protein acetylation P53, P21 and P16 expressions in young and senile mice, protein expression of telomerase reverse transcriptase (TERT) as well as reactive oxygen species (ROS) level were detected and compared; the expression of BMMSCs autophagy associated gene, autophagy related protein molecule and LC3 molecule were detected; the influence of differently concentrated rapamycin and 3-MA on BMMSCs autophagy level was observed to select effective concentrations; the influence of rapamycin and 3-MA on BMMSCs cell cycle-related gene expression, apoptosis related gene expression and ROS level were discussed. Results revealed that the senile BMMSCs group had higher acetylation P53, P21 and P16 expression and fluorescence intensity than the young group, but its TERT expression, Beclin1 and LC3 gene expression and fluorescence intensity were lower than the young group. Both rapamycin and 3-MA inhibited CyclinD1 (CCND1) and CyclinD2 (CCND2) expression. Rapamycin promoted the expression of apoptosis-related genes Caspase3 and Caspase8 in the senile group, while 3-MA inhibited them in both the young and senile groups. It can therefore be concluded that senile BMMSCs have multiple age-related changes, performing as decrease of osteogenic capability and multiplication capacity, increase of acetylation P53, P21 and P16 protein expression, apoptosis and ROS level as well as decrease of telomerase activity. Furthermore, the autophagy level in senile BMMSCs reduced compared with young cells; autophagy activation can decrease ROS level and autophagy suppression improves ROS level; and autophagy regulation affects cell cycle and apoptosis.