Effects of gonadotropin-inhibitory hormone on testicular development and reproduction-related gene expression in roosters.

Gonadotropin-inhibitory hormone (GnIH) plays a crucial role in regulating reproduction in the hypothalamus of poultry and has been intensely investigated since its discovery. This study aimed to assess the effects of GnIH on testicular development, as well as on reproduction-related hormone release and gene expression levels in roosters. The administration of exogenous GnIH resulted in a significant reduction in testis weight, testis volume and semen quality (p < 0.05). Additionally, exogenous GnIH significantly up-regulates the expression of GnIH, and down-regulates the expression of PRL (p < 0.05). GnIH application also decreased the GnRH, vasoactive intestinal peptide (VIP) and luteinizing hormone ß subunit(LHß)gene expression levels. Meanwhile, by neutralizing the effects of endogenous GnIH through immunization, testicular development on day 150 in roosters was significantly promoted. Compared to the control condition, GnIH immunization significantly down-regulated the expression of the VIP and PRL genes (p < 0.05). In conclusion, we found that exogenous GnIH treatment inhibited testicular development, reduces PRL gene expression, and suppressed reproductive performance in roosters. Conversely, GnIH immunization down-regulated VIP and PRL genes, activates the reproductive system, and promotes the reproductive activity and testicular development of roosters.

[The influence of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-time gynecological laparoscopic tumor surgery].

Objective: To investigate the effect of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-term gynecological laparoscopic tumor surgery. Methods: A total of 57 patients who underwent gynecological tumor surgery in Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine from May to October 2022 were prospectively included. The patients were randomly divided into two groups: the precise blood pressure management group [group P, n=28, aged (69.9±3.6) years] and the control group [group C, n=29, aged (68.6±3.1) years]. Group P adopted a precise blood pressure management scheme, and systolic blood pressure (SBP) fluctuated within±10% of basal blood pressure during operation, while group C adopted a routine blood pressure management scheme, which maintained SBP fluctuation within±20% of basal blood pressure during operation, and SBP≥90 mmHg (1 mmHg=0.133 kPa). The main outcome measures were the quality of anesthesia recovery (QoR-40) scores of the two groups 24 hours after the operation. The secondary outcome measures included lactate clearance rate and blood glucose change 2 hours after the beginning of the operation and immediately after the operation, post anesthesia recovery score (PARS) and sedation-agitation scale (SAS) 5 min after extubation, intraoperative norepinephrine dosage, volume of fluid administered, blood loss and urine volume, creatinine clearance rate and urea nitrogen clearance rate 24 hours after the operation, anesthesia satisfaction score, length of hospital stay and hospitalization cost, etc. Results: The QoR-40 score of group P [M (Q1, Q3)] 24 hours after operation was 192 (190, 195), which was higher than that of group C [170 (163, 178)] (P<0.001). The lactate clearance rates 2 hours after the beginning of the operation and immediately after the operation in group P [M (Q1, Q3)] were 31.0% (14.9%, 43.3%) and 21.1% (3.1%, 38.2%), which were higher than those in group C [-12.5% (-43.1%, 11.8%) and -22.2% (-61.3%, -11.1%)] (both P<0.05). The changes in blood glucose 2 hours after the beginning of the operation and immediately after the operation in group P [M (Q1, Q3)] were [1.1 (0.9, 1.4) mmol/L and 1.4 (0.9, 1.9) mmol/L], which were higher than those in group C [0.2 (-0.2, 0.5) mmol/L and 0.2 (-0.2, 0.5) mmol/L] (both P<0.05). The intraoperative urine volume, PARS score and SAS score 5 min after extubation, and anesthesia satisfaction score in group P [M (Q1, Q3)] were 400 (300, 500) ml, 8 (8, 9), 4 (4, 4) and 8 (8, 9), respectively, which were higher than those in group C [200 (100, 300) ml, 7 (7, 8), 3 (3, 3) and 6 (6, 7), respectively] (all P<0.05). There were no statistically significant differences in norepinephrine dosage, volume of fluid administered, blood loss, creatinine clearance rate, urea nitrogen clearance rate, length of hospital stay and hospitalization cost between the two groups (all P>0.05). Conclusion: The precise blood pressure management scheme of maintaining SBP fluctuation within±10% of basal blood pressure in elderly patients undergoing long-time gynecological laparoscopic tumor surgery can significantly enhance the quality of postoperative anesthesia recovery, improve the patients' satisfaction, and facilitate the patients' postoperative rehabilitation.

[Benchmark dose estimation of polycyclic aromatic hydrocarbons exposure base on Bayesian kernel machine regression].

Objective: To explore benchmark dose (BMD) estimations of polycyclic aromatic hydrocarbons (PAHs) based on Bayesian kernel machine regression (BKMR) . Methods: A total of 155 adult residents of a coking plant in Shanxi Province who were surveyed in summer (June to August) from 2014 to 2019 were selected as the research objects. Fasting elbow vein blood of the subjects was collected in the morning for automatic analysis and detection of blood routine. Morning urine samples were collected for automatic analysis and detection of urine routine and urine creatinine detection. BKMR model combined with BMD method was used to calculate the acceptable doses of PAHs exposure on red blood cell damage in non-occupational population. Results: The concentration of hydroxylpolycyclic aromatic hydrocarbons (OH-PAHs) in the red blood cells abnormal group (n=117) was significantly higher than that in the normal group (n=38) (P<0.01). In the combined effect of OH-PAHs, 2-hydrol-naphthalene contributed the most, and the posterior inclusion probability (PIP) value was 0.9354. When OH-PAHs ≥P(55) concentration, the joint effect on the risk of red blood cell abnormalities increased as the concentration of the OH-PAHs mixture increased. When OH-PAHs were at P(65) and P(75) concentrations, respectively, the risk of red blood cell abnormalities in adults were 3.09 and 4.98 times that of OH-PAHs at P(50) concentrations, respectively. Compared with high concentration, low concentration of OH-PAHs exposure was more sensitive to red blood cell darmage. The acceptable doses of 8 kinds of OH-PAHs were 1.010 µmol/mol Cr (2-hydrol-naphthalene), 0.743 µmol/mol Cr (1-hydrol-naphthalene), 0.901 µmol/mol Cr (2-hydroxy-fluorene) and 0.775 µmol/mol Cr (1-hydroxy-phenanthrene), 0.737 µmol/mol Cr (1-hydroxy-pyrene), 0.607 µmol/mol Cr (9-hydroxy-fluorene), 0.713 µmol/mol Cr (2-hydroxy-phenanthrene) and 0.628 µmol/mol Cr (3-hydroxybenzo[a] pyrene), respectively. Conclusion: OH-PAHs mixture has positive combined effect on red blood cell damage in non-occupational population, and low concentration of OH-PAHs exposure is more sensitive to red blood cell damage. It is recommended that the exposure dose of PAHs should be controlled within 1 µmol/mol Cr.

[Clinical efficacy of transjugular intrahepatic portosystemic shunt for gastrointestinal hemorrhage in patients with idiopathic noncirrhotic portal hypertension].

Objective: To explore the medium-long term efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for gastrointestinal hemorrhage in patients with idiopathic non-cirrhotic portal hypertension (INCPH). Methods: From March 2013 to July 2018, clinical data of 13 INCPH patients, including 5 males, 8 females,with gastrointestinal hemorrhage were retrospectively analyzed, who were diagnosed at the First Affiliated Hospital of Zhengzhou University, Anyang Fifth People' s Hospital and Yuncheng Central Hospital. All patients received TIPS treatment. The general information, postoperative survival rate, the incidence of rebleeding, shunt dysfunction rate, and incidence of hepatic encephalopathy were analyzed. Results: All 13 patients with INCPH completed TIPS successfully with an average age of 45±8 (33 to 59) years. The hepatic venous pressure gradient (HVPG) decreased from 20.0-26.0 (22.6±1.9) mmHg before procedure to 8.0-14.0 (9.4±3.2) mmHg after. The median follow-up time was 44±7 (31 to 53) months. One patient died of liver failure 27 months after TIPS. Hepatic encephalopathy occurred cumulatively in 1 case (1/13), 1 case (1/13) and 1 case (1/13) in 12, 24 and 36 months after TIPS. Stent restenosis occurred cumulatively in 2 cases (2/13), 3 cases (3/13) and 3 cases (3/13) in 12, 24 and 36 months after TIPS. Portal vein thrombosis occurred cumulatively in 2 cases (2/13), and no primary liver cancer developed. Conclusions: TIPS is safe and effective in the treatment of INCPH with gastrointestinal bleeding with favorable medium-long term outcome.

[Correlation between thyroid function and glucolipid metabolism in type 1 diabetic adults].

To assess the correlation between thyroid function and glucolipid metabolism in type 1 diabetic adults. A retrospective analysis was conducted in 230 type 1 diabetic adults who were hospitalized in the Department of Endocrinology of Shandong Provincial Hospital Affiliated to Shandong University from January 2008 to January 2020. It showed that thyroid stimulating hormone(TSH) was significantly positively correlated with total cholesterol (TC) (r=0.239), triglycerides (TG) (r=0.166) and low-density lipoprotein cholesterol (LDL-C) (r=0.249), respectively (all P<0.05). Free triiodothyronine (FT3) was significantly negatively correlated with fasting plasma glucose (FPG) (r=-0.272), glycated hemoglobin (HbA1c) (r=-0.240), TC (r=-0.197) and LDL-C (r=-0.220), respectively (all P<0.05). Free thyroxine (FT4) was negatively correlated with TC (r=-0.171) and LDL-C (r=-0.170), respectively (all P<0.05). TC was an independent predictor of TSH, FT3 and FT4, FT3 and FT4 were independent predictors of HbA1c. TSH was an independent predictor of TC, TG and LDL-C. Thyroid function is closely related to glucolipid metabolism in type 1 diabetic adults.

[Clinical and laboratory characteristics of rheumatoid arthritis with positive antinuclear antibody].

OBJECTIVE: To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. RESULTS: The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ2=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ2=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ2=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ2=25.743, P < 0.01, 74.9% vs. 59.4%, χ2=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×109±104.6×109) vs. (295.9×109±100.1×109) /L, t=-2.970, P < 0.01, respectively]. CONCLUSION: The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.

[Establishment of percutaneous nephrolithotomy pathway guided by C-arm CT].

Objective: To investigate the feasibility and advantages of establishing percutaneous nephrolithotomy pathway guided by C-arm CT. Methods: The data of 258 patients who were established a percutaneous nephrolithotomy pathway under the guidance of C-arm CT in the Department of Interventional Medicine of the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2019 were retrospectively analyzed, including168 males and 90 females, and aged 19-88 (60±11) years. There were 84 cases of single stone, 174 cases of multiple stone, and 18 cases of cast stone. The stone size was 9-42 (22±6) mm. Among them, dual access was established in 18 cases, and nephrolithotomy access was established in 276 cases. The three-dimensional guiding function of C-arm CT was used to puncture the target calyces and establish the percutaneous nephrolithotomy pathway. Results: The pathway was successfully established in 258 cases at the first time, with a success rate of 93.5%; successfully established in 15 cases at the second time, with a success rate of 98.9%; and unable to establish in 3 cases, with a failure rate of 1.1%. The operation time was (7.9-32.5) min, with an average of (16±5) min. The lithotripsy time was (25-115) min, with an average of (43±8) min. The intraoperative blood lose was (45-420) ml, with an average of (75±11) ml. There were 23 cases with postoperative calculus residual (8.3%). Postoperative complications included fever in 86 cases (33.3%), which improved after symptomatic treatment. Postoperative hematuria was observed in 128 patients (49.6%) with varying degrees of gross hematuria, among which 2 patients (0.72%) were treated with arterial embolization due to excessive bleeding and ineffective conservative treatment, while the hematuria disappeared after symptomatic treatment in the rest of the patients. Conclusion: The method of establishing percutaneous nephrolithotomy pathway under the guidance of C-arm CT was simple to operate. Especially for patients without hydronephrosis, this method had a high success rate and low complications, which was worthy of clinical promotion and reference.

[Application of aldosterone/direct renin ratio before drug washout in the screening of primary aldosteronism].

Objective: To explore the cut-off point of aldosterone/direct renin ratio (ADRR) before drug washout in the screening for primary aldosteronism (PA) in the Chinese population and reduce the potential risk caused by drug washout during PA screening. Methods: Hospitalized hypertensive patients in the Hypertension Ward of Fuwai Hospital, Chinese Academy of Medical Sciences from January 2017 to October 2019 were enrolled. PA was diagnosed according to the criterion of 2016 American Guideline and 2016 Chinese Consensus for PA. The plasma aldosterone concentration (PAC), direct renin concentration (DRC) and ADRR before and after drug washout were measured. The receiver operating characteristic (ROC) curve of ADRR was drawn and the maximal Youden index was used to determine the best cut-off value. Results: A total of 542 hypertensive patients were included, with 467 patients diagnosed with essential hypertension (EHT) (297 males and 170 females), and 75 patients diagnosed with PA (51 males and 24 females). Patients with PA had higher PAC and ADRR before and after drug washout than those with EHT(150.0 (130.0, 210.0) vs 120.0 (80.0, 170.0) ng/L, 170.0 (120.0, 260.0) vs 130.0 (90.0, 180.0) ng/L; 28.9 (15.9, 63.5) vs 4.3 (1.9, 11.8) (ng/L) / (mU/L) , 55.6 (39.0, 109.0) vs 9.8 (4.5, 21.3) (ng/L) /(mU/L), all P<0.001). However, DRC of PA patients before and after washout were lower than those with EHT (4.0 (2.0, 10.0) vs 27.0 (10.0, 64.0) mU/L, 3.0 (2.0, 4.0) vs 12.2 (5.0, 27.0) mU/L, P<0.001). In EHT and PA groups, PAC and ADRR significantly increased (P=0.001, P<0.001) , but DRC significantly decreased after drug washout (all P<0.001) . The area under the ROC curve of ADRR before drug washout was 0.868 (95%CI 0.836-0.895) with the best cut-off value of 7.8 (ng/L) / (mU/L) for the screening of PA .The sensitivity and specificity was 94.7% and 66.8%, respectively, with the maximal Youden index of 0.615. Conclusion: ADRR before drug washout > 7.8 (ng/L) / (mU/L) can be used as an alternative cut-off point to screen PA when drug washout is not available.

[A novel mutation of SCN4A gene causes hypokalemic periodic paralysis in a Chinese family].

Objective: To report a Chinese family with hypokalemic periodic paralysis (HOKPP) and investigate the clinical and pathogenic gene characteristics of the family. Methods: The clinical, electrophysiological and pathological data of the proband of the family were analyzed, and the information of the family was investigated in detail. The peripheral venous blood of the six members of the family was collected and their genomic DNA was extracted. The genes related to periodic paralysis analysis of the proband were performed by the second generation sequencing. The pathogenicity of the mutant protein was respectively analyzed by the bioinformatics software SIFT, Polyphen2 and Mutation Tasker. The cosegregation analysis of phenotype and genotype of the family was performed by the first generation sequencing. Results: There were 3 patients in the family with the onset age of 21 to 42 years old. All the patients manifested with vomiting as the first symptoms, then presented with muscle weakness accompanied by muscle soreness. The muscle weakness gradually relieved in 3 to 5 days. Creatine kinase (CK) of the proband significantly increased. Electromyographic exercise test was positive, however, electromyography and muscle pathological analysis were normal. The genes related to periodic paralysis analysis of the proband found a novel mutation (c.2458A>T (p.N.820Y)) of SCN4A gene which was located in the conservative region. The function analysis showed it was a pathogenic mutation. Moreover, the first generation sequencing confirmed that the mutation was cosegregated with patients in the family. Meanwhile, it was found that the proband's son carried the same mutation, but without any symptom, indicating that he was a pre-symptomatic patient. Conclusions: Vomiting can be one of the symptoms of the patients with HOKPP. The novel mutation of SCN4A gene c.2458 A>T is the pathogenic mutation of the family. Patients with periodic paralysis should be tested for blood potassium and genes as early as possible to facilitate early diagnosis and genetic counseling.

[Clinical characteristics of elderly and younger onset rheumatoid arthritis].

Objective: To compare the clinical and laboratory characteristics and therapy methods of elderly onset rheumatoid arthritis (EORA) and younger onset rheumatoid arthritis (YORA). Methods: The clinical, laboratory and therapeutic data of 481 RA patients in the Department of Rheumatology and Immunology in Peking University Third Hospital from January 2013 to December 2018 were collected and used to analyze the difference of characteristics between EORA group and YORA group, which might be useful for better diagnosis and treatment of EORA patients. Quantitative data of normal distribution were compared with t test between the two groups. Results: There were 481 patients in this cohort, of which 137(28.5%) were EORA, 344(71.5%) were YORA, with a mean age of (59±14) years (19-87 years). There were 358 females (74.4%) and 123 males (25.6%). The percentage of male patients was obviously higher in EORA group (36.5% vs 21.2%, χ(2)=12.012, P<0.01), and the average disease course was obviously shorter (Z=-7.985, P<0.01). Disease Activity Score 28 (DAS28) score was higher in EORA group (5.6±1.3 vs 5.2±1.6, t=2.549, P<0.05), meanwhile the incidences of pleural effusion and interstitial lung disease (ILD) were higher (6.6% vs 1.7%, 29.9% vs 18.3%, respectively; χ(2)=7.550, 7.797, both P<0.05). The incidences of venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, coronary heart disease (CHD), peripheral atherosclerosis and cataract in EORA group were all significantly higher than those in YORA group (all P<0.05). Erythrocyte sedimentation rate (ESR) and D-Dimer in EORA group were all remarkably higher (both P<0.05). The rate of using glucocorticoid in EORA group was higher but the rate of using methotrexate and anti-tumor necrosis factor-α agents were lower (χ(2)=5.271, 8.407, 9.356, all P<0.05). Conclusion: Compared to YORA group, the percentage of male patients and disease activity of EORA group are higher. The occurrence of pleural effusion, ILD, venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, CHD, peripheral atherosclerosis and cataract in EORA group are higher than those in YORA group.

[Study of reactive oxygen species and adiponectin for chronic HBV infection combined with nonalcoholic fatty liver diseases].

Objective: To investigate the application value of reactive oxygen species (ROS) and adiponectin (ADPN) in the judgment of liver inflammation in chronic hepatitis B virus infection combined with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 159 cases with NAFLD (21 cases), chronic hepatitis B virus infection (57 cases), and chronic hepatitis B virus infection combined with NAFLD (81 cases) were collected between June 2016 to December 2018, and the visited patients diagnosis were confirmed by histopathological examination of the liver. ROS and ADPN level retained in serum was determined by enzyme-linked immunosorbent assay. Histopathological examination of liver tissue was used as the gold standard to discuss the diagnostic value of the serum in patients with chronic hepatitis B virus infection combined with NAFLD for the occurrence of nonalcoholic steatohepatitis. One-way analysis of variance was used for the comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups. Measurement data for non-normal distributions were expressed as M (P25, P75). Comparisons between groups were performed using the Mann-Whitney U or Kruskal-Wallis H test. Chi-square test was used to compare the count data between groups. Correlation analysis was performed using Spearman correlation analysis. Histopathological grouping of liver tissue was used as the gold standard, and the area under the receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the regression formula. Results: (1) In patients with chronic hepatitis B virus infection combined with NAFLD, the levels of ROS in the non-hepatic steatosis group and the mild hepatic steatosis group were significantly lower than those in the moderate and severe hepatic steatosis group, while the ADPN level in the non-hepatic steatosis group was significantly higher than liver steatosis group, P < 0.05. (2) The results of correlation analysis showed that ROS was significantly correlated with NAS score, change in the degree of fatty liver and lobular inflammation (all P < 0.05).There was a significant negative correlation between ADPN and the change in the degree of fatty liver (P < 0.05). (3) Logistic regression analysis results showed that the diagnostic formula for chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis was 0.02 × controlled attenuation index + 0.584 × white blood cells/10(9) + 0.587 × ROS-10.982. The area under receiver operating characteristic curve of the subject was = 0.896. The sensitivity, specificity, positive and negative predictive value were 97.1%, 71.2%, 64.2%, and 97.9%. Conclusion: ADPN and ROS have certain reference value in differentiating the change in the degree of fatty liver and inflammation in chronic hepatitis B virus infection combined with NAFLD and the diagnostic formula has higher application value in the diagnosis and exclusion of chronic hepatitis B virus infection combined with nonalcoholic steatohepatitis.

[Association of Urinary Phenol Concentration and Blood Biochemical Indices in Coke Oven Workers].

Objective: To explore the association of urinary phenol concentration and blood biochemical indices in coke oven workers. Methods: From April to may 2019, we investigated 771 employing coke oven workers from a coke plant in Taiyuan city, and categorized into benzene-exposed group (n=402) and control group (n=369) based on their benzene exposures in workplace and urophenol concentrations. All subjects were interviewed face-to-face using a questionnaire including name, age (year) , gender, smoking and drinking habits, personal vocational history, working length (year) , and occupational protection, etc. Post-shift urine samples detected using a gas chromatography-hydrogen flame ionization detector. Fasting venous blood was drawn in the morning and centrifuged, the separated serum were detected the following items using an automatic blood biochemistry analyzer. Covariance and multiple linear regression were used to test the association of urinary phenol concentration and the levels of all the blood biochemical indices. Results: The subjects were predominantly males (n=719, 93.3%) , with an average age of (42.3±8.2) years and an average working length of (20.6±8.2) years. Compared with the control group, the benzene-exposed group were significantly different in age, working length of years, gender, smoking and drinking habits (P<0.05) . The median (interquartile interval) concentration of urinary phenol was 6.00 (0.00-33.00) µg/ml in the benzene-exposed group, which was significantly higher than that in the control group (P<0.05) . Covariance analysis indicated that the fasting blood glucose, total cholesterol and high density cholesterol in the benzene-exposed group were significantly reduced compared with the control group, yet the serum creatinine, serum uric acid and triglyceride were significantly increased (P<0.05) . Multiple linear regression showed that, an increase of each natural logarithm (Ln) transformed urinary phenol concentration was significantly associated with increases in serum uric acid level [9.82 (95%CI: 2.18-17.47) µmol/L] and cholesterol level[0.10 (95%CI:0.00-0.20) mmol/L]. An increase of each Ln-transformed accumulated benzene exposure levels was significantly associated with an increase in total cholesterol level[0.09 (95%CI: 0.01-0.17) mmol/L]. Conclusion: Occupational benzene exposure is possibly related to the variation of purine and total cholesterol metabolism in coke oven workers.

Improving the performance of optical antenna for optical phased arrays through high-contrast grating structure on SOI substrate.

A novel optical antenna for optical phased arrays is proposed and simulated. A high-contrast grating structure is used to achieve extremely efficient emission. The emission efficiency is as high as 93.94% at 1.55 µm, which exceeds 50% in a range of wavelength from 1.48 µm to 1.62 µm. The antenna can achieve a perfect grating lobe suppression with background suppression of 28.4 dB when the phase difference between adjacent waveguides is 0. A 16-wire optical phased array can easily achieve a scan range of ± 22.8° × 20.2° with a beam width of 2.4° × 2.5°, by employing the optical antenna proposed.

Subtype-specific inherited predisposition to pemphigus in the Chinese population.

BACKGROUND: Pemphigus is a group of rare life-threatening mucocutaneous autoimmune diseases, presenting mainly as two subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Inherited predispositions to pemphigus have long been speculated but they remain poorly understood. OBJECTIVES: To identify common and specific nongenetic and genetic factors associated with pemphigus and its subtypes in the Chinese population. METHODS: A genome-wide association study (GWAS) was performed in 496 unrelated patients with pemphigus (including 365 with PV and 104 with PF) and 1105 controls without pemphigus. RESULTS: A sex preference was observed only in PV (57·5% female) and not in PF (47·1% female). For male patients only, the mean age at diagnosis was significantly lower for PV than for PF (P < 0·001). The strongest associated single-nucleotide polymorphisms are in the human leucocyte antigen (HLA) region: rs70993900 (PV; P = 1·5 × 10-45 ) and rs9469220 (PF; P = 1·1 × 10-8 ). HLA-DQB1*05:03 ranks at the top (P = 4·7 × 10-40 ; odds ratio 12·4) in both subtypes, with significantly different risk allele frequency (RAFPV = 34·2% vs. RAFPF = 18·8% vs. RAFcontrol = 4·4%), whereas HLA-DRB1*14:01 and HLA-DRB1*04:06 are PV specific. HLA-DQB1*03:03 and HLA-DQB1*03:02 show significant subtype specificity in opposite directions. All of these associations were validated in the replication series with 147 cases of pemphigus and 604 controls. Multiple novel non-HLA susceptibility loci were also identified in the GWAS. CONCLUSIONS: This study represents the largest GWAS on pemphigus in the Chinese population published to date, and has allowed us to identify HLA haplotypes significantly shared between or specific to the two main subtypes of pemphigus.

ROR2 modulates neuropathic pain via phosphorylation of NMDA receptor subunit GluN2B in rats.

BACKGROUND: Neuropathic pain, a type of chronic pain as a result of direct central or peripheral nerve damage, is associated with significant quality of life and functional impairment. Its underlying mechanisms remain unclear. We investigated whether ROR2, a member of the receptor tyrosine kinase-like orphan receptor (ROR) family, participates in modulation of neuropathic pain. METHODS: Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and von Frey filament testing. Immunofluorescence staining was used to detect expression of ROR2 in neuronal nuclei. Fos expression was determined by immunocytochemistry. Phosphorylation status was detected by western blot and immunoprecipitation. Small interfering RNA was used to knock down ROR2 expression. RESULTS: ROR2 was upregulated and activated in spinal neurones after chronic constriction injury (CCI) in mice [1.3 (0.1) to 2.1 (0.1)-fold of sham, P<0.01] from Day 1-21. CCI induced significant demethylation of the CpG island in the ROR2 gene promoter [0.37 (0.06) vs 0.12 (0.03)% CpG methylation, P<0.001]. Knockdown of ROR2 in the spinal cord prevented and reversed CCI-induced pain behaviours and spinal neuronal sensitisation [Fos expression: 130 (12) vs 81 (8) cells, P<0.05; 120 (11) vs 70 (7) cells, P<0.05]. In contrast, activation of spinal ROR2 by intrathecal injection of Wnt5a induced pain behaviours and spinal neuronal sensitisation [Fos expression: 11 (1) vs 100 (12) cells, P<0.001] in wild-type mice. Furthermore, ROR2-mediated pain modulation required phosphorylation of N-methyl-D-aspartate receptor 2B subunit (GluN2B) at Ser 1303 and Tyr1472 by pathways involving protein kinase C (PKC) and Src family kinases. Intrathecal injection of GluN2B, PKC, or Src family kinase-specific inhibitors significantly attenuated Wnt5a-induced pain behaviours. CONCLUSIONS: ROR2 in the spinal cord regulates neuropathic pain via phosphorylation of GluN2B, suggesting a potential target for prevention and relief of neuropathic pain.

First case of Rubinstein-Taybi syndrome with desquamation associated with a novel mutation in the bromodomain of the CREBBP gene.

Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder, mainly characterized by postnatal growth retardation, intellectual disability, and facial and limb abnormalities. Although not considered as characteristic manifestations, numerous cutaneous anomalies have also been reported in patients with RSTS while there has been no report of desquamation so far in any patients with RSTS. We report an unusual case of RSTS in an 8-year-old boy who presented with the typical facial and limb abnormalities of RSTS accompanied with apparent hirsutism and desquamation, but without apparent intellectual disability. Whole exome sequencing identified a novel mutation in the bromodomain of CREBBP (c.3503A>G, p.N1168S), which was further confirmed by targeted Sanger sequencing in comparison with healthy controls. Our findings expand the spectra of genetic mutations and clinical presentations associated with RSTS, and underline the importance of maintaining high awareness of rare presentations and diagnostic difficulties in management of rare genetic diseases such as RSTS.

Comparative evaluation of GPR versus APRI and FIB-4 in predicting different levels of liver fibrosis of chronic hepatitis B.

It is of great significance to develop and evaluate noninvasive indexes predicting the level of liver fibrosis. The aim of this study was to comparatively evaluate gamma-glutamyl transpeptidase-to-platelet ratio (GPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on 4 factors (FIB-4) in predicting different levels of liver fibrosis of chronic hepatitis B (CHB) within the framework of HBeAg-positive and HBeAg-negative patients. A total of 1157 HBeAg-positive and 859 HBeAg-negative CHB patients were enrolled, among whom the pathological stage ≥S2, ≥S3, ≥S4 were defined as significant fibrosis, extensive fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curves were used to evaluate the performance of GPR, APRI and FIB-4 in predicting different levels of liver fibrosis. In HBeAg-positive patients, the area under ROC curves (AUROCs) of GPR in predicting extensive fibrosis and cirrhosis were both significantly larger than those of APRI (P = .0001 and P < .0001). In HBeAg-negative patients, the AUROCs of GPR in predicting significant fibrosis and cirrhosis were significantly larger than those of FIB-4 (P = .0006 and P = .0041). The AUROC of GPR in predicting extensive fibrosis was significantly larger than that of APRI and FIB-4 (P = .0320 and P = .0018). Using a cut-off of GPR > 0.500 as standard, the sensitivities and specificities of GPR in predicting significant fibrosis in HBeAg-positive patients were 59.6% and 81.2%, and for cirrhosis 80.9% and 63.8%, respectively; and those of HBeAg-negative patients were 60.3% and 78.3%, 84.5% and 66.1%, respectively. Regardless of HBeAg-positive or HBeAg-negative status, GPR had the best performance in predicting different levels of liver fibrosis.

Bombyx mori cyclin-dependent kinase inhibitor is involved in regulation of the silkworm cell cycle.

Cyclin-dependent kinase inhibitors (CKIs) are negative regulators of the cell cycle. They can bind to cyclin-dependent kinase (CDK)-cyclin complexes and inhibit CDK activities. We identified a single homologous gene of the CDK interacting protein/kinase inhibitory protein (Cip/Kip) family, BmCKI, in the silkworm, Bombyx mori. The gene transcribes two splice variants: a 654-bp-long BmCKI-L (the longer splice variant) encoding a protein with 217 amino acids and a 579-bp-long BmCKI-S (the shorter splice variant) encoding a protein with 192 amino acids. BmCKI-L and BmCKI-S contain the Cip/Kip family conserved cyclin-binding domain and the CDK-binding domain. They are localized in the nucleus and have an unconventional bipartite nuclear localization signal at amino acid residues 181-210. Overexpression of BmCKI-L or BmCKI-S affected cell cycle progression; the cell cycle was arrested in the first gap phase of cell cycle (G1). RNA interference of BmCKI-L or BmCKI-S led to cells accumulating in the second gap phase and the mitotic phase of cell cycle (G2/M). Both BmCKI-L and BmCKI-S are involved in cell cycle regulation and probably have similar effects. The transgenic silkworm with BmCKI-L overexpression (BmCKI-L-OE), exhibited embryonic lethal, larva developmental retardation and lethal phenotypes. These results suggest that BmCKI-L might regulate the growth and development of silkworm. These findings clarify the function of CKIs and increase our understanding of cell cycle regulation in the silkworm.

[The clinical significance of circulating follicular helper T cells in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis].

Objective: To investigate the change of circulating follicular helper T cells (cTfh) in patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis (MPO-AAV), and to analyze the relationship between cTfh and disease activity. Methods: Thirty-eight untreated MPO-AAV patients (patient group) and thirty-eight healthy volunteers (control group) were enrolled in this study. cTfh and membrane expression of inducible co-stimulator (ICOS) and programmed cell death protein 1 (PD-1) were detected by flow cytometry (FCM). Serum anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA) was measured by ELISA. Disease activity was evaluated by Birmingham vasculitis activity score (BVAS). Results: Compared with those in control group, the proportions of cTfh, ICOS(+)Tfh and PD-1(+) Tfh cells in patient group were significantly higher [(25.9±3.8)% vs. (21.0±5.3)%, P<0.001; (1.8±0.8)% vs. (0.8±0.5)%, P<0.001 and (10.2±2.8)% vs. (8.2±2.2)%, P=0.001, respectively]. Meanwhile, the expression of ICOS and PD-1 on cTfh in patient group was markedly more intensive (59.6±10.0 vs.49.2±6.9, P<0.001 and 532.6±104.2 vs. 485.1±73.4, P=0.025, respectively). In patient group, the proportion of cTfh was positively correlated with the ratio of ICOS(+)Tfh, the expression of ICOS, the level of MPO-ANCA and BVAS (r=0.407, P=0.011; r=0.705, P<0.001; r=0.737, P<0.001 and r=0.663, P<0.001, respectively). The expression intensity of ICOS on cTfh was positively associated with ICOS(+)Tfh ratio, serum MPO-ANCA and BVAS (r=0.388, P=0.016; r=0.645, P<0.001 and r=0.653, P<0.001, respectively). Nevertheless, the expression of PD-1 on cTfh was only positively correlated with the ratio of PD-1(+) Tfh (r=0.473, P=0.003). Conclusions: Enhanced cTfh in patients with MPO-AAV might produce MPO-ANCA, which is related to the aggravation of MPO-AAV. Thus, cTfh and its ICOS could be potentially targeted for the treatment of MPO-AAV.