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OBJECTIVE: To explore the efficacy of voriconazole combined with glucocorticoid on the nephrotic syndrome in children. PATIENTS AND METHODS: A total of 62 children with nephrotic syndrome were enrolled in this study. They were treated in our hospital from February 2016 to August 2019, including 35 children treated with voriconazole in a control group, and 27 children treated with glucocorticoid combined with voriconazole in a research group. The efficacy was evaluated, and a logistic regression analysis was carried out to find out the risk factors affecting the efficacy. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum creatinine and urine protein expression before and after treatment. In addition, receiver operating characteristic (ROC) curves were drawn to analyze the predictive value of serum creatinine and urine protein expression. RESULTS: The marked efficacy and total effective rate in the research group were significantly higher than those in the control group, while the non-efficacy in the research group was significantly lower than that in the control group (p<0.05). After treatment, the expression of serum creatinine and urine protein in the research group was significantly lower than that in the control group (p<0.05). The area under the curve (AUC) of urine protein was 0.798. The AUC of serum creatinine was 0.724. Multivariate logistic regression analysis revealed that serum albumin, high edema, infection, serum creatinine, and urine protein were independent risk factors. CONCLUSIONS: Glucocorticoid can improve clinical efficacy. Serum creatinine and urine protein can be adopted as predictive factors for efficacy on children with nephrotic syndrome. Serum albumin, high edema, infection, serum creatinine, and urine protein were independent risk factors for the efficacy on children with nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Background: The most common type of male infertility is asthenospermia. We cloned DnaJ heat shock protein family member B13 (Dnajb13/DNAJB13), a type II HSP40 family member that is highly expressed in the testis. DNAJB13 plays a crucial role in sperm flagellar function. Objectives: The aim of this study was to investigate whether a correlation exists between DNAJB13 and low sperm motility in infertile men. Materials and methods: In the present study, we performed a mutation screening of the DNAJB13 gene in 92 idiopathic asthenozoospermia patients and 200 men with normal fertility. Additionally, we used immunoelectron microscopy, co‐immunoprecipitation, mass spectrometric detection, indirect immunofluorescence assay, transmission electron microscopy studies, isobaric tags for relative and absolute quantitation, and multiple reaction monitoring studies to analyze changes in DNAJB13 protein. Results: A novel c.106T>C mutation of DNAJB13 was present in nearly 10% (9/92) of idiopathic asthenozoospermia patients and was absent in 200 fertile men. A computer‐assisted sperm analyzer and transmission electron microscopy analysis using samples from 9 patients with DNAJB13 mutations demonstrated that most spermatozoa were immotile due to sperm tail defects. Multiple reaction monitoring results indicated that DNAJB13 protein levels were reduced after gene mutation. We achieved a pregnancy rate of 100% in 8 patients with DNAJB13 mutations using ICSI. Discussion and conclusion: The DNAJB13 heterozygous variant may affect fertility. ICSI can help these patients with low fertility to father children. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma genitalium infection is significantly associated with an increased risk of male infertility. To date, few large M. genitalium studies have been conducted in China. Objective: This study aimed to estimate the M. genitalium incidence and treatment failure and to provide information regarding the resistance of M. genitalium to macrolide and tetracycline antibiotics among men of infertile couples in China. Materials and Methods: This study was performed as a retrospective survey of seminal and meatus urinarius secreta specimens of 30,094 men of infertile couples collected and used for microbiological tests for the evaluation of genital tract infections (Mycoplasma genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae) between October 2016 and December 2017. Mycoplasma genitalium RNA was detected using novel simultaneous amplification testing. Macrolide and tetracycline resistance screening was introduced using polymerase chain reaction (PCR) and Sanger sequencing. Results: The incidence of M. genitalium was 2.49% (749 of 30,094; 95% confidence interval (CI), 2.31–2.66%). After antibiotic treatment, the mean values of semen parameters increased from those measured before treatment. The overall incidence of treatment failure was 17.56% (82/467; 95% CI, 14.10%–21.02%) (112−26−4 = 82), irrespective of the drug used. Resistance to macrolide and tetracycline antibiotics was detected in 58 samples (58/60, 96.67%; 95% CI, 91.99–101.34%) and 27 samples (27/60, 45.00%; 95% CI, 32.04–57.96%), respectively. Conclusions: Although the M. genitalium incidence was relatively low, the detection of macrolide antibiotic resistance in >96.67% of the treatment failure samples most likely explained the high azithromycin treatment failure rate (73/195, 37.44%) in our study. These findings indicate the need to provide resistance testing and to reappraise the recommended antimicrobial options in China. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ischemic postconditioning (IPO) reduces lethal reperfusion injury under normal conditions, but its effectiveness is blocked by hypercholesterolemia (HC). This study aims to determine whether blocking the mitochondrial permeability transition pore (mPTP) with cyclosporine-A (CsA) can restore cardioprotection of IPO in hypercholesterolemic rat heart. MATERIALS AND METHODS: Isolated rat hearts underwent 30 min global ischemia and 120 min reperfusion. Postconditioning protocol was induced by six cycles of 10s ischemia and 10s reperfusion at the onset of the reperfusion. CsA (0.5 µM or 5 µM) was administered 15 minutes before ischemia. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining. Cardiomyocyte apoptosis was assessed by TUNEL staining and creatine kinase-MB (CK-MB) was analyzed from coronary effluent. RESULTS: In normocholesterolemia (NC) groups, infarct size, cardiomyocyte apoptosis rate and release of CK-MB were significantly reduced after IPO. These reductions were completely abolished by HC, as evidenced by a similar infarct size, cardiomyocyte apoptosis rate and release of CK-MB observed between IPO-HC group and control-NC group, but were restored by IPO combinated with CsA treatment. However, CsA treatment alone could not restore cardioprotection in a state of HC. CONCLUSIONS: Ischemic postconditioning, blocked by hypercholesterolemia may due to the excessive opening of the mPTP. Inhibiting of the mPTP with CsA is able to reverse this loss of cardioprotection. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ischemic postconditioning (IPO) and pharmacological pretreatment may reduce myocardial necrosis and apoptosis during ischemia/reperfusion. This study aimed to determine the protective effect of fasudil pretreatment combined with IPO on myocardial ischemia/reperfusion injury in rats and explore the possible mechanisms. MATERIALS AND METHODS: The SD rats were induced by intraperitoneal injection of fasudil hydrochloride (1 or 10 mg/kg) 60 min before the initiation of ischemia, while the control rats were given the same volume of saline. The hearts were hung on the Langendorff perfusion apparatus and underwent 30 min global ischemia and 120 min reperfusion. The IPO protocol was induced by six cycles of 10 sec ischemia and 10 sec reperfusion at the onset of reperfusion. The hemodynamic changes were measured, myocardial infarct size was determined by triphenyltetrazolium chloride (TTC) staining, cardiomyocyte apoptosis was detected by TUNEL staining, lactate dehydrogenase (LDH) was analyzed from coronary effluents, phosphorylation of Akt and eNOS, as well as expression of Bcl-2 and Bax were measured by western blotting analysis. RESULTS: The high-dose fasudil (10 mg/kg) pretreatment group and IPO group significantly improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the control group (p < 0.05). In addition, the high-dose fasudil pretreatment combined with IPO group could further improved post-ischemia cardiac function, reduced myocardial infarct size, attenuated cardiomyocyte apoptosis, decreased the release of LDH, increased expression of phospho-Akt, phospho-eNOS and Bcl-2, and reduced expression of Bax compared with the single treatment groups (p < 0.05). CONCLUSIONS: The combination of high-dose fasudil pretreatment and IPO had a synergistic protective effect on myocardial ischemia/reperfusion injury, which was mediated via upregulating the PI3K/Akt/eNOS pathway, increasing expression of antiapoptotic Bcl-2, and decreasing expression of proapoptotic Bax. [ABSTRACT FROM AUTHOR]

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BSTRACT [ABSTRACT FROM AUTHOR]

Introduction: Mouse mTSARG3 and human homogenous gene TSARG6 are new cloned genes specially expressed in the testis. Previous experiments showed that the mTSARG3 protein has interactions with Hsp90, Hsp70 and androgen receptor (AR) proteins. To demonstrate the function of TSARG6 and AR during human spermatogenesis, we used DHPLC, restriction enzyme cutting and direct sequencing to screen Chinese patients with oligozoospermia, azoospermia or androgen insensitivity syndrome (AIS). Materials/Methods: Peripheral blood samples, including 100 patients with oligozoospermia or azoospermia and 100 normal Chinese males as controls, were collected and their gDNA were extracted. Eight exons of TSARG6 gene were amplified by polymerase chain reaction (PCR), then denaturing high performance liquid chromatography (DHPLC) screening was performed, followed by restriction enzyme cutting and direct sequencing to detect point mutations. Results: Five SNP in exon 2 (including rs10793069, rs10793068 and rs625098, 2 newfound SNP), one synonymous mutation, three SNP in exon 8 (including rs2306820, rs2306819, 1 newfound SNP) of TSARG6 were found in patients. A missense mutation S36P was found in a patient with azoospermia and a patient with AIS while no mutations were found in 100 normal males. Conclusions: TSARG6 has been proved to be related to human spermatogenesis. The mutation of amino acids may influence the integrating of androgen and androgen receptor. [ABSTRACT FROM AUTHOR]

Introduction: mTSARG3 is a new cloned gene specially expressed in the mouse testis whose function is related to apoptosis. In previous work we found a mutation in an azoospermic patient. The aim of the present study was to transfect wild and mutant cDNA of mTSARG3 into GC-1spg cell line to explore its function. Materials/Methods: Site-directed mutagenesis was used to mutate serine 36 to a proline residue of mTSARG3 protein. GC- 1 cells were stably transfected with pcDNA3.1 Hygro(-) empty vector, wild-type mTSARG3, and mutant mTSARG3 using lipofectamine 2000. Western blot, and real-time PCR were used to determine the expression of target protein or mRNA of mTSARG3.To further assess the effects of the mTSARG3 mutant on cell cycle pattern and apoptosis, flow cytometry analysis was performed. The experiments were repeated in duplicate and a standard two-tailed Student's t-test was use to analyse the data. Results: Wild and mutant mTSARG3 cDNA was successfully cloned into the eukaryotic expression vector pcDNA3.1 Hygro(-). Three stable cells clone transfected with cDNAs including empty vector, wild and mutant mTSARG3 were obtained and overexpression of mTSARG3 protein was observed. pcDNA3.1(-)/ mTSARG3 was successfully transfected into GC-1spg cell line and showed stable expression in this cell line. Flow cytometry analysis revealed that in the mutant mTSARG3 transfected cell group, the number of cells in G0/G1 phase increased (P < 0.05), the apoptotic rate of the mutant mTSARG3 transfected cell group increased (P < 0.05) compared with the other groups (empty and wild type). Conclusions: The establishment of a stable transfected mTSARG3 cell line may be a promising cell model for studying the biological function of the mTSARG3 gene. The increment in apoptosis caused by the mutation found in the human homologue is related to azoospermia. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t -test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant ( t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant ( t : IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.

Objective: To explore the difficulties and surgical decision of laparoscopic technique in patients with complicated hepatolithiasis. Methods: The clinical data of 13 patients with complicated hepatolithiasis who underwent laparoscopic hepatectomy at Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College from December 2019 to December 2020 were collected. There were 3 males and 10 females with average age of 50.8 years (range: 14 to 67 years). All patients had upper abdominal pain and a history of cholecystectomy, 4 of them had fever.Seven cases underwent laparoscopic left hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic right hemihepatectomy+bile duct exploration, 2 cases underwent laparoscopic quadrate hepatectomy (liver 4B+Part 5)+hilar cholangioplasty+bile duct exploration, 2 cases underwent laparoscopic quadrate lobe resection (liver 4B+Part 5)+cholangioplasty+cholangiojejunostomy. All patients were re-examined with abdominal ultrasound and choledochoscope 3 months after operation. Results: The median operation time was 5.2 hours (range: 3.6-6.5 hours), blood loss was 278 ml (range: 120-580 ml). During the operation, 1 case had duodenal bulb injury, and the defect area was about 1.0 cm × 1.2 cm. After timely detection, the defect area was carefully evaluated and trimmed. Absorbable suture was used to suture duodenal bulb, and gastrojejunostomy was performed after repair. One case had small intestinal serosa injury, which was intermittently sutured and embedded with absorbable suture. All the patients recovered smoothly without death. Three months after the operation, 12 patients completed abdominal ultrasound and T-tube sinus choledochoscopy. Residual stones were found in 3 patients, stones were removed in 2 patients by T-tube sinus choledochoscopy 3 months after the operation, 1 patient was still in the recovery period (within 3 months after surgery). No residual stones were found in the remaining 10 patients. Conclusion: The three key laparoscopic techniques in operation of complex hepatolithiasis: adhesiolysis and porta hepatis exposure, laparoscopic hepatectomy, and laparoscopic choledochojejunostomy are very important.

Objective: To investigate the diagnosis method of Gilbert syndrome (GS) and the relationship between UGT1A1 gene polymorphism distribution with serum bilirubin. Methods: Clinical data of 115 GS cases diagnosed in our hospital from January 2013 to November 2018 were retrospectively analyzed. Chi-square test, Fisher's exact probability method, t-test, and non-parametric test were used for data analysis. Results: 115 cases with GS had an average age of (36.89 ± 12.77) years and an average serum total bilirubin level of (44.01 ± 18.78) μmol/L.UGT1A1*28/*28 (21, 18.3%), UGT1A1*1/*28 (17, 14.8%), and UGT1A1*1/*6 (17, 14.8%) were the most common single-site mutations. UGT1A1*1/*28 + *1/*6 (26, 22.6%), UGT1A1*28/*28 + *1/*27 (5, 4.3%) and UGT1A1*1/*28 + *1/*6 + *1/* 27 (5, 4.3%) were the most common multiple-site mutations. Among 110 cases with Gilbert syndrome combined with non-hemolytic diseases, pairwise comparisons showed that the total bilirubin levels of patients with UGT1A1*28/*28 mutations were significantly higher than UGT1A1*6/*6 and UGT1A1*1/*28 + *1/*6 mutation ( P < 0.05). Additionally, with the increase of UGT1A1*28 distribution, the serum total bilirubin level had gradually increased ( P = 0.028), but UGT1A1*6 was opposite ( P = 0.021). There were no significant differences in gene distribution and bilirubin level between GS group (67 cases) and GS combined with viral hepatitis group (32 cases) ( P > 0.05). Conclusion: UGT1A1 gene sequencing detection is a simple, safe, specific and sensitive effective method to assist GS diagnosis. It can reduce the misdiagnosis and mistreatment of clinical jaundice, thus reducing the patients' psychological burden and saving the limited medical resources. It is worthy of clinical application.

Objective: To summarize and analyze the clinical efficacy of 3D and 2D laparoscopic surgery in thyroidectomy for thyroid cancer. Method: Thirty-seven patients with early-differentiated thyroid cancer underwent laparoscopic surgery from August 2016 to November 2018. Their clinical data were retrospectively analyzed. They were divided into 3D laparoscopic group and 2D laparoscopic group based on laparoscopic imaging systems. The perioperative clinical indicators and postoperative complications of the two groups were compared. Result: Compared with the 2D laparoscopic group, the 3D laparoscopic group had shorter operation time and less bleeding, and the incidence of postoperative complications was less, but the differences between the two groups were not statistically significant( P >0.05). Conclusion: Compared with the 2D laparoscopic thyroidectomy, 3D laparoscopic thyroidectomy for thyroid cancer allows higher surgical precision, shorter operation time, lower operation risk and smoother surgical procedure, thus improves surgical efficiency., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To analyze peripheral blood interleukin-6 (IL-6) promoter DNA methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). Methods: Blood samples of 41 adult patients with SLE and 20 healthy controls were collected.The methylation status of IL-6 promoter was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR.Correlations between IL-6 promoter methylation status and clinical features or laboratory findings in patients with SLE were analyzed. Results: The levels of IL-6 mRNA were significantly higher in peripheral blood of SLE.DNA methylation levels of IL-6 promoter were reduced in SLE patients as compared with healthy controls.The methylation status and expression of IL-6 in peripheral blood reflected the levels in peripheral blood mononuclear cells (PBMCs). Significantly positive correlation was found between IL-6 hypomethylation and renal disorder, as well as hypocomplementemia in patients with SLE. Conclusion: Hypomethylation of interleukin-6 promoter in peripheral blood might be involved in the etiology of SLE.

Background: Calcium-activated chloride channels (CLCAs) have been found to be preferentially expressed on the secretory epithelium. They may play a pivotal role in mucous overproduction by bronchial goblet cells in asthma. It has been reported that the inhibition of CLCAs with niflumic acid could relieve the symptoms of asthma. However, niflumic acid has serious adverse effects. DNA vaccination is considered to be a promising strategy to treat allergic diseases such as asthma and dust mite allergy., Methods: We constructed a vaccine encoding human CLCA1 (hCLCA1) and evaluated its effects on promoting antibodies against hCLCA1 and the related preventive function in a mouse model of asthma., Results: Our results reveal that the induced hCLCA1 antibodies can be detected in the first 2 weeks after immunization with hCLCA1 plasmids (hCLCA1-p) by intramuscular injection and augmented gradually in the following several weeks. The autoantibodies against hCLCA1 induced by the DNA vaccine bound to three segments of the mouse CLCA3 (mCLCA3) protein, including the amino terminal (PepN), the carboxyl terminal (PepC) and the middle of the protein (PepM). In our study, mice immunized with hCLCA1-p developed fewer pathological changes compared with other control groups, including a remarkable reduction in the air pressure-time index of the trachea, the number of eosinophils and mast cells in the bronchoalveolar lavage fluid and the mRNA level of MUC5AC in goblet cells., Conclusion: Taken together, our results suggest that a DNA vaccine encoding the CLCA protein may have potential as a useful pharmacotherapy for asthma in the future., (Copyright © 2013 S. Karger AG, Basel.)

Background: Excessive airway mucus secretion is a remarkable trait of asthma. Mucus overproduction mainly resulted from an increase in goblet cell numbers, which causes considerable damage to health. However, effective therapeutic treatments are still lacking for mucus hypersecretion. Human calcium-activated chloride channel 1 (hCLCA1) has been identified to be predominantly responsible for mucus hypersecretion., Objectives: In this study, we investigated the effects of an hCLCA1 DNA vaccine on the control of mucus production and goblet cell proliferation using an in vitro model goblet cell line (NCI-H292)., Methods: The effect of the hCLCA1 DNA vaccine on cell viability and proliferative activity of NCI-H292/hCLCA1 was analyzed by electron microscopy, MTT assay, and flow cytometry. Expression of mucins and MUC5AC, a major member of the mucin gene family in airway goblet cells, was assessed under hCLCA1 DNA vaccine challenges by periodic acid-Schiff staining, quantitative real-time PCR and Western blot, respectively, and the expression profile of granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine in airway inflammation, was also examined by real-time PCR and immunocytochemistry., Results: Results showed that hCLCA1 overexpression caused high cell proliferation and mucin expression, whereas the hCLCA1 DNA vaccine could effectively reverse these abnormal effects. In addition, GM-CSF expression was highly induced by hCLCA1 overexpression and efficiently suppressed by hCLCA1 DNA vaccine., Conclusions: These results illustrate that the hCLCA1 DNA vaccine effectively inhibits cell hyperplasia and mucin gene expression of goblet cells, suggesting that the hCLCA1 DNA vaccine has potential value in the treatment of human asthma., (Copyright © 2013 S. Karger AG, Basel.)

Benzo[a]pyrene-r-7,t-8,9,c-10-tetrahydrotetrol (100 pg, 342 fmol) was measured using the following sequence of steps: (1) chemical transformation with potassium superoxide to 2,3-pyrenedicarboxylic acid; (2) electrophore derivatization with pentafluorobenzyl bromide; (3) sample clean-up by high-performance liquid chromatography and (4) measurement by gas chromatography with electron-capture detection and by gas chromatography with electron-capture negative-ion mass spectrometry. The overall, absolute yields obtained by the two procedures were 69% and 60%, respectively. This work completes the first stage towards the establishment of a general method for detecting diolepoxide polyaromatic hydrocarbon DNA adducts by gas chromatography.

The pharmacokinetics of SC1001-Sodium and SC1001-Aminum in the human body was studied. After 200 mg SC1001-Sodium or SC1001-Aminum by oral administration, plasma concentration-time data were fitted to curves by means of the nonlinear least-square method, employing the program we ourselves compiled. With F-test, comparing gamma 2(1) -value and AIC-value, the linear one compartment open model was available. The mean pharmacokinetic parameters fitted one by one were as follows with the first value given belonging to SC1001-Sodium and the second to SC1001-Aminum: Ka: 0.7248 and 0.5102 h-1; Ke: 0.0597 and 0.1149 h-1; T1/2, a: 1.1437 and 1.8999 h; T1/2, e: 15.7428 and 6.1497 h; AUC: 600.15 and 28.61 micrograms.h/ml; Tm: 4.4798 and 4.3728h.