High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

PURPOSE: Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. METHODS: A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). RESULTS: Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. CONCLUSION: We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

[Identification of lymph node metastasis related genes in prostate cancer using weighted gene co-expression network analysis].

Objective: To explore the molecular markers related to lymph node metastasis of prostate cancer (PCa) based on bioinformatics technology and carry out clinical verification. Methods: The differentially expressed genes of PCa with lymph node metastasis were screened from geo data, and the hub genes of the gene co expression network were constructed. The hub genes were incorporated into the support vector machine model to evaluate its prediction efficiency. The hub genes were verified in the TCGA data set and analyzed for immune infiltration. The clinical data of 80 patients with prostate cancer in the Fourth Hospital of Hebei Medical University from January 2019 to December 2022 were collected. The logistic risk model was used to evaluate the prediction efficiency of hub gene metastasis. Results: Five hub genes (GSK3B, TP53, PSMC6, SUMO1, PIK3CA) were identified, and the support vector machine model constructed by them had good diagnostic value (the accuracy rate was 83.87%). TCGA validation results showed that only PSMC6 was significantly differentially expressed in PCa tissues with lymph node metastasis (P<0.001). The results of immune infiltration analysis showed that the expression of PSMC6 was significantly correlated with 9 kinds of immune cells (B cells, DC, IDC, etc.). Clinical information analysis showed that the expression of PSMC6 was significantly correlated with lymph node metastasis, PSA value, T stage and Gleason score (P<0.01). Univariate logistic results showed that T stage (OR=3.230, 95%CI:1.192-8.757, P=0.021), Gleason score (OR=4.627, 95%CI:2.212-9.677, P<0.001), PSMC6 (OR=25.235, 95%CI:5.326-119.560, P<0.001) could be used as predictors of lymph node metastasis. Multivariate logistic analysis showed that PSMC6 (OR=16.537, 95%CI:2.928-93.393, P=0.001) could be used as an independent risk factor for predicting lymph node metastasis. Conclusion: PSMC6 may be used as a potential molecular marker for judging lymph node metastasis in patients with PCa.

[Distribution characteristics of tumor infiltrating lymphocytes in EBV-associated lymphoepithelioma-like carcinoma and their clinical significance].

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

Precision Measurement of the Lamb Shift in Muonium.

We report a new measurement of the n=2 Lamb shift in Muonium. Our result of 1047.2(2.3)_{stat}(1.1)_{syst} MHz comprises an order of magnitude improvement upon the previous best measurement. This value matches the theoretical calculation within 1 standard deviation allowing us to set limits on Lorentz and CPT violation in the muonic sector, as well as on new physics coupled to muons and electrons which could provide an explanation of the muon g-2 anomaly.

Sex-specific metabolic risk factors and their trajectories towards the non-alcoholic fatty liver disease incidence.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. This study examined sex-specific associations between NAFLD and metabolic factors and investigated the trajectory of risk factors. METHODS: We retrospectively investigated 16,140 individuals from Beijing Health Management Cohort. Univariate and multivariate time-dependent Cox regression analyses were performed to identify independent risk factors for new-onset NAFLD. The trajectory of risk factors was investigated using the latent growth curve model and growth mixture model. RESULTS: Over a median follow-up of 3.15 years, 2,450 (15.18%) participants developed NAFLD. The risk factors for NAFLD in men were increased body mass index (BMI); waist circumference (WC); triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin (Hb), and serum uric acid (SUA) levels; and platelet (PLT) count and decreased serum creatinine-to-body weight (sCr/bw) and high-density lipoprotein cholesterol (HDL-C) levels. In women, the risk factors were increased BMI, WC, and fasting plasma glucose (FPG), TG, LDL-C, SUA, white blood cell (WBC), and PLT and decreased sCr/bw and HDL-C levels. In addition, BMI, LDL-C, sCr/bw and PLT changing trajectories were associated with NAFLD in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends was associated with NAFLD risk in women. CONCLUSIONS: Development of NAFLD is associated with BMI, LDL-C, sCr/bw and PLT changing trajectories in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends are associated an increased risk of NAFLD in women. Deterioration of metabolic risk factors status can be a predictor of NAFLD many years before its occurrence.

[An epigenetic clock model for assessing the human biological age of healthy aging].

Objective: To construct an epigenetic clock model for assessing and calibrating human biological age. Methods: Convenience sampling was used to select 186 subjects from the longevity cohort of Guangxi Zhuang Antonornous Region from July 1 to November 30, 2019, and 124 subjects from the physical examination population of the Seventh Medical Center of the PLA General Hospital from October 1 to December 31, 2020. Self-designed questionnaire was applied to collect demographic characteristics and family history of disease. Physical examination was applied to determine heart rate and blood pressure. Fasting peripheral venous blood was drawn for determination of fasting plasma glucose, plasma total cholesterol, triglyceride, plasma high-density lipoprotein cholesterol, plasma low-density lipoprotein cholesterol and telomere length. Methylation levels of EDARADD cg09809672, IPO8 cg19722847, NHLRC1 cg22736354, P2RX6 cg05442902 and SCGN cg06493994 were detected by targeted methylation site sequencing. A total of 54 subjects with unqualified quality control of DNA methylation and telomere length were excluded, and 256 subjects' data were finally analyzed. Trend test was used for the change of methylation level among different ages groups, multiple linear regression method was used to build prediction models of biological age. Kendal rank correlation analysis was used to evaluate the correlation of age gap (Gregorian calendar age minus biological age) with telomere length. Independent sample t-test was used to compare the health-related indicators between subjects with different age gap within different age groups. Results: The M(Q1, Q3)of age of subjects were 67 (51, 91) years old, including 166 females (64.84%). With increase of age, the methylation levels of gene loci were decreased (EDARADD cg09809672, IPO8 cg19722847 and P2RX6 cg05442902) and increased (NHLRC1 cg22736354 and SCGN cg06493994) (all P values<0.05). The established biological age prediction model was as follows: Y=-53.121×EDARADD cg09809672-137.564×IPO8 cg19722847+141.040×NHLRC1 cg22736354-67.893×P2RX6 cg05442902+149.547×SCGNcg06493994+4.592×sex+64.185 (R2=0.86, P<0.001), where Y was the biological age, and the items in the equation were methylation level, sex (male =1, female =2) and intercept in sequence. The Kendall rank correlation coefficient between age gap and telomere length was 0.731 (P<0.001). Compared with the subjects whose age gaP<0, the subjects with age gaP≥0 had higher systolic blood pressure in adolescence [(88.50±8.89) and (109.83±9.48) mmHg, respectively, 1 mmHg=0.133 kPa]; lower TC [(5.48±0.23) and (3.98±0.54) mmol/L, respectively, ] and TG [(3.51±0.32) and (3.41±0.20) mmol/L] in young adults; lower fasting blood glucose in middle age [(6.17±0.67) and (5.37±0.79) mmol/L, respectively, ] and higher diastolic blood pressure in nonagenarian age [(76.99±6.78) and (83.97±9.36) mmHg, respectively, ] (all P values<0.05). Conclusion: The constructed epigenetic clock model can be used to evaluate and calibrate human biological age.

[Application progress of home self-sampling for human papillomavirus and human immunodeficiency virus testing].

Self-sampling is a method by which the subject collects the own specimens for disease detection. It has the advantages of strong privacy, convenient and simple operation, free time and place, etc. It can improve the compliance of people in remote areas, affected by traditional concepts, limited by working hours and underdeveloped transportation and medical treatment to participate in disease detection and screening. With the development of "Internet+health care" and "Internet+nursing service", home-based self-sampling testing will become a developing situation for disease detection and screening. Human immunodeficiency virus and Human papillomavirus infection bring a heavy burden to individuals and society. In the absence of effective and widespread primary prevention, secondary prevention, namely "early detection, early diagnosis and early treatment" is an effective measure to control the adverse consequences. At present, there are many researches on HPV and HIV self-sampling test, whose test results are highly reliable and highly accepted in the population, and is of great significance for improving the coverage rate of cervical cancer screening and the diagnosis rate of HIV carriers.

Genome editing efficiency of four Drosophila suzukii endogenous U6 promoters.

The invasive spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae) has caused serious economic losses to the fruit industry. The conventional control methods have many limitations and genetic engineering technologies such as CRISPR/Cas9-mediated gene drive are promising approaches. In the CRISPR/Cas9 system, the transcriptional regulatory elements play an important role in the activities of gRNA. Thus, in order to improve the genome editing efficiency of the CRISPR/Cas9 system in D. suzukii, we cloned and tested four endogenous U6 promoters to drive mutagenesis of the white gene. Our results showed that all the four promoters could be used with variable efficiency. The promoter DsU6-3 had the highest genome editing efficiency among the four DsU6 promoters. Compared with the DsU6-3 promoter, the DmU6:3 promoter showed lower efficiency to drive mutagenesis in D. suzukii. These findings expand the range of promoters available to express gRNAs in D. suzukii, facilitating the basic and applied research on this important pest.

[Differential diagnosis of pure ground glass nodules in lung with spectral CT imaging].

Objective: To evaluate the differential diagnostic performance of quantitative parameters derived from the spectral CT imagingin pure ground-glass nodules. Methods: A total of 44 patients with pure ground glass nodules underwent chest energy spectrum CT and with known subsequently pathological findings in the Imaging Department of the Second Affiliated Hospital of Soochow University from August 2017 to September 2019 were retrospectively analyzed. Among them, there are 18 males and 26 females, aged from 26 to 79 (51±12) years. They were divided into as the inflammatory group (n=12), pre-invasive adenocarcinoma group (n=17) and invasive adenocarcinoma group (n=15). The aforementioned three groups were further reclassified as non-invasive adenocarcinoma group (inflammatory lesion+pre-invasive lesion) and invasive adenocarcinoma group in order to evaluating the values of water concentration (WC) for the determination of adenocarcinoma infiltration status. The values of WC derived from the arterial and venous phase of the lesion, iodine concentration (IC), standardized iodine concentration (NIC) were measured respectively.The slope of the energy spectral curve (K40-70KeV) derived from the arterial and venous phase of the lesion was also calculated. One-way ANOVA analysis was performed to compare the differences of the three groups and the multiple comparison method was used for further comparing. Intraclass correlation efficient (ICC) was used to assess the consistency of the three times of measurements. The area under curve(AUC) of Receiver Operating Characteristic (ROC) was conducted to evaluate the diagnostic performance of water based values. Results: The values of WC in the arterial and venous phases were significantly different. As in the inflammatory group, the pre-invasive lesion group and the invasive adenocarcinoma group, the values of WC was (291.95±58.66) mg/cm3, (297.61±63.96) mg/cm3and (374.52±60.62) mg/cm3 of the arterial phase, and (277.07±33.78) mg/cm3, (291.74±50.49) mg/cm3 and (373.33±75.12) mg/cm3 of the venous phase, respectively(all P<0.05). Further comparison demonstrated that no significant difference was observed for the values of WC derived from the arterial phases and venous phases between the inflammatory lesion group and the pre-invasive lesion group (all P>0.05).There were an significant differences between the invasive adenocarcinoma group, the inflammatory lesion group and the pre-invasive lesion group (all P<0.05). The values of WC derived from the venous phase achieved the largest AUC (0.770) for differentiating invasive adenocarcinoma from non-invasive adenocarcinoma (inflammatory lesions+pre-invasive lesions) in the pure ground glass nodules. The sensitivity and specificity were 66.67% and 93.10%, respectively, when using 349.31 mg/cm³ as the optimal threshold. The slope of the spectral curve and iodine-related parameters (IC, NIC) derived from arterial or venous phases among the three groups were not significantly different (all P>0.05). Conclusion: The values of WC derived from the spectral CT can better distinguish inflammatory, pre-invasive lesions and invasive adenocarcinoma, which is helpful for the qualitative analysis for pure ground glass nodules.

[On-site epidemiological investigation of a carbon monoxide poisoning incident].

Nighteen people at a restaurant experienced dizziness headaches and other discomforts in six days. According to the description method, the time and location distribution were found to be concentrated. A second Investigation was conducted at the same time as the onset of the case, the test found that the carbon monoxide concentration of second floor up to 539 mg/m(3). The on-site testing found that when 2 steam generator in snack room on the first floor turned on, the carbon monoxide concentration on the top of elevator on the second floor was 1225.0 mg/m(3). After the accident, the restaurant replaced a steam generator, the carbon monoxide concentration on the top of the new and old steam generator were 350 mg/m(3) and >1 000 mg/m(3), respectively. After the steam generators were fitted with exhaust smoke pipe and exhasust hood, the carbon monoxide concentrations of on the top of the vegetable transfer elevator and the room on the second floor were both 0.4 mg/m(3), and there were no cases of recurrence. It was determined that this was a carbon monoxide poisoning incident caused by a high concentration of carbon monoxide emitted by the steam generators, which spread to the second floor of the private room through the vegetable transfer elevator.

Risk factors for death from hand-foot-mouth disease: a meta-analysis.

In recent years, outbreaks of hand-foot-mouth disease (HFMD) in China, Singapore and other Western Pacific Region, involving millions of children, have become a big threat to public health. This study aimed to quantitatively assess all qualified studies and identify the risk factors for HFMD death. A systematic search of the databases PubMed, Medline, Embase and the Cochrane Library was performed. Study heterogeneity and publication bias were estimated. Seven case-control studies involving 1641 participants (634 died and 1007 survived) were included in the meta-analysis. Human enterovirus 71 infection, male, age ⩽3 years, vomiting, cyanosis, convulsion, duration of fever ⩾3 days, atypical rashes and abdominal distention were not significantly related to HFMD death (P ⩽ 0.05). Lethargy (odds ratio (OR) = 6.62; 95% CI 3.61-12.14; I2 = 0%; P < 0.0001), pneumonoedema/pneumorrhagia (OR = 4.09; 95% CI 2.44-6.87; I2 = 0%; P < 0.0001), seizures (OR = 6.85; 95% CI 2.37-19.74; I2 = 0%; P = 0.0004), dyspnoea (OR = 8.24; 95% CI 2.05-33.19; I2 = 83%; P = 0.003) and coma (OR = 3.76; 95% CI 1.85-7.67; I2 = 0%; P = 0.0003) were significantly associated with HFMD death, which were risk factors for HFMD death.

CRISPR/Cas9-mediated knockout of the eye pigmentation gene white leads to alterations in colour of head spots in the oriental fruit fly, Bactrocera dorsalis.

The intensely studied white gene is widely used as a genetic marker in Drosophila melanogaster. Here, we cloned and characterized the white gene in an important pest of the fruit industry, Bactrocera dorsalis, to understand its functional role in pigmentation. We obtained BdWhite knockout strains, based on the wild-type strain, using the CRISPR/Cas9 genome editing system, and found that mutants lost pigmentation in the compound eye and their black head spots. We then examined differences in the expression levels of genes associated with melanin pigmentation between mutants and the wild-type strain using quantitative reverse transcription PCR. We found that transcription levels of the Bd-yellow1 were lower in the head of mutants than in the wild-type strain, and there were no significant differences in expression of the other six genes between mutants and the wild type. Since yellow is critical for melanin biosynthesis (Heinze et al., Scientific Reports. 2017;7:4582), the lower levels of expression of Bd-yellow1 in mutants led to reduced dark pigmentation in head spots. Our results provide the first evidence, to our knowledge, that white may play a functional role in cuticle pigmentation by affecting the expression of yellow.

[Diagnostic value of gadobenate dimeglumine enhanced MRI in hepatic fibrosis of rats].

Objective: To evaluate the value of Gd-BOPTA enhanced MRI in the staging of liver fibrosis. Method: Fifty male SD rats (6-week-old, 180-220 g) were divided into the modeling group (n=42) and the control group (n=8). The model of liver fibrosis in the modeling group was established by carbon tetrachloride (animal license No. SYXK (Su) 2017-0043). From week 2 to week 10, rats in the modeling group (n=4) and control group (n=1) were randomly selected to scan 1 h(RER1), 2 h(RER2) and 3 h(RER3) after injection of Gd-BOPTA, respectively, to measure the relative enhancement rate (RER) of liver parenchyma. The shape of intrahepatic bile duct and the degree of enhancement at each time point were observed. Results: Forty-two rats (34 rats in the modeling group and 8 rats in the control group) completed the experiment. RER1, RER2 and RER3 of the control group were 1.44±0.37, 1.22±0.37 and 0.84±0.28 respectively. RER1, RER2 and RER3 of the modeling group were respectively: S1 (n=6): 1.49±0.48, 1.29±0.39, 0.91±0.38;S2 (n=9): 1.48±0.44, 1.34±0.37, 1.04±0.40;S3 (n=11): 1.49±0.43, 1.37±0.39, 1.21±0.30; S4 (n=8): 1.49±0.44, 1.40±0.37, 1.24±0.40. There was no significant difference in RER1 and RER2 values between the control group and the liver fibrosis group (F=0.022, P=0.999; F=0.301, P=0.875). There were significant differences between the control group and RER3 values of hepatic fibrosis stage S3 and S4 (t=2.249, P=0.031; t=2.274, P=0.029), there was no significant difference between the remaining groups (all P>0.05).In the control group, the intrahepatic bile duct was obviously strengthened within 1 hour after enhancement, and walked naturally. The intrahepatic bile duct was slightly enhanced 1h after the enhancement of S3-S4 stage of hepatic fibrosis, and the intrahepatic bile duct was significantly enhanced 2-3 hours later, with distorted alignment. Conclusion: Delayed 3 hours liver parenchymal RER and intrahepatic bile duct distortion delay enhancement after Gd-BOPTA enhancement contribute to the S3-S4 diagnosis of liver fibrosis.

[Clinicopathologic features and prognosis of patients with IgA nephropathy superimposed on transplant glomerulopathy].

Objective: To observe the clinicopathologic features and prognostic of patients with IgA nephropathy (IgAN) superimposed on transplant glomerulopathy (TG+ IgAN). Methods: Electronic medical records of Jinling Hospital were searched for TG+ IgAN patients that was diagnosed during January 2004 to December 2016. Clinicopathologic features and prognoses information were retrieved and analyzed. The primary outcome was initiation of replacement therapy or an eGFR declined to<15 ml·min(-1)·(1.73m(2))(-1). Results: A total of 49 patients with pathologically confirmed TG+ IgAN were enrolled in this study. The median time from renal transplantation to allograft biopsy was 85 months. There were 131 patients with TG in the control group. There was no statistical difference in the age, gender, and immunosuppressive regimen during renal biopsy in the two groups. In TG+ IgAN patients, the median serum creatinine level was 175 µmol/L, the median urinary protein was 1.45 g/24 h, and 16.3% of the patients had nephrotic range proteinuria, the incidence of microscopic hematuria was 40.8%, and the average hemoglobin was 105 g/L. In terms of pathology, the degree of glomerular mesangial matrix hyperplasia in the TG+ IgAN group was significantly heavier compared with TG group (P=0.004), and the degree of hyaline degeneration of the small arteries was lighter (P=0.043). There was no significant difference in interstitial inflammation (i), tubulitis (t), glomerulitis (g), peritubular capillaritis (ptc) and intimal arteritis (v). Calculated by Kaplan-Meier method, the median survival time of 49 patients with TG+ IgAN was 36.9 months, and there was no difference in survival rate of allografts compared with TG group. Conclusions: Compared with TG patients without IgA, TG+ IgAN patients had higher incidence of microscopic hematuria, more severe glomerular mesangial matrix hyperplasia, and no significant differences in other clinicopathological features. The prognosis of TG+ IgAN patients was not significantly different from those without IgAN.

[Relationship between morphological characteristics and prognosis of non-nasopharyneal EBV-associated carcinoma].

Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.

MicroRNA-548-3p and MicroRNA-576-5p enhance the migration and invasion of esophageal squamous cell carcinoma cells via NRIP1 down-regulation.

Nuclear receptor interacting protein (NRIP1), also known as RIP140, is a transcriptional co-regulator required for the maintenance of energy homeostasis and ovulation. Although several studies have identified roles for NRIP1 in various cell processes, the biological functions of NRIP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. Herein, we demonstrate that NRIP1 inhibits the migration and invasion of ESCC cells. Further mechanistic studies revealed that NRIP1 is directly targeted by miR-548-3p and miR-576-5p. We then identified that miR-548-3p and miR-576-5p regulate the migration and invasion of ESCC cells by inhibiting NRIP1 expression. Interestingly, the expression of miR-548-3p and miR-576-5p in ESCC cell lines and ESCC tissues is up-regulated and NRIP1 is down-regulated relative to controls. A statistically significant inverse association was found between the expression levels of miR-548-3p/miR-576-5p and NRIP1. These combined results reveal novel functions for miR-548-3p, miR-576-5p, and NRIP1 in regulating ESCC cell migration and invasion which are important functions for the metastatic process in esophageal cancer.

Efficacy and safety of sublingual immunotherapy with Dermatophagoides farinae drops in pre-school and school-age children with allergic rhinitis.

BACKGROUND: The safety and efficacy of sublingual immunotherapy (SLIT) have been confirmed by many studies. However, in China, the research on efficacy and safety in young and older children with allergic rhinitis (AR) is still rare. OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy and safety of SLIT with Dermatophagoides farinae drops in pre-school and school-age children with AR. METHODS: A total of 282 subjects aged 2-13 years with AR received a two-year course of sublingual immunotherapy along with pharmacotherapy. According to the age, patients were defined as the pre-school group (2-6 years old, n=116) and school-age group (7-13 years old, n=166). Total nasal rhinitis symptom scores (TNSS), visual analogue score (VAS) and total medication scores (TMS) were evaluated at four time points: baseline, after SLIT for half a year, one year and two years. The adverse events (AEs) were evaluated at each visit. RESULTS: After two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were significantly lower than baseline (all P<0.05). The comparison of efficacy between one and two-year duration showed no significant difference in global clinical outcomes (all P>0.05). In addition, there were no significant differences between the pre-school and school-age group in TNSS (all P>0.05), VAS (all P>0.05) and TMS scores (P>0.05) after SLIT for half a year, one year and two years. No severe systemic AEs were reported. CONCLUSION: SLIT with D. farinae drops is clinically effective and safe in pre-school and school-age patients with house dust mites (HDMs)-induced AR.

Lactobacillus plantarum BS22 promotes gut microbial homeostasis in broiler chickens exposed to aflatoxin B1.

Probiotics promote the health of the host by maintaining intestinal microbial homeostasis. This study aimed to investigate the benefits of Lactobacillus plantarum BS22 (LP) in the gastrointestinal tract (GIT) microbial homeostasis of broiler chickens exposed to aflatoxin B1 using the PCR-DGGE, viable count and real-time PCR. The toxin adsorption experiment demonstrated that treatment R5 (1.0 × 108 CFU/g LP) exhibited good absorptive effect in adsorbing the aflatoxin B1 (AFB1 ) in vitro. DGGE showed that the composition and structure of gut microbiota were more similar in the mucosa than in the content of all the samples. In addition, higher diversity of the microbiota was observed in the caecum and glandular stomach than in other segments. Lactobacillus, Enterococcus and Enterobacteriaceae were more abundant in the ileum than in the other segments. Enterobacteriaceae in groups I (basal diet) and II (basal diet+50 µg/kg AFB1 ) showed a significant difference in group III (basal diet + 50 µg/kg AFB1  + 1 × 108 CFU/g LP) in the crop content and duodenum mucosa (p < .05). This investigation indicates that the L. plantarum BS22 promotes GIT microbial homeostasis in broiler chickens exposed to AFB1 , particularly for the intestine mucosa microbiota. Thus, L. plantarum BS22 is a possible candidate for degrading AFB1.