Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. METHODS: In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to WHO BMI classifications. RESULTS: Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). CONCLUSION: Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

All-Optical GeV Electron Bunch Generation in a Laser-Plasma Accelerator via Truncated-Channel Injection.

We describe a simple scheme, truncated-channel injection, to inject electrons directly into the wakefield driven by a high-intensity laser pulse guided in an all-optical plasma channel. We use this approach to generate dark-current-free 1.2 GeV, 4.5% relative energy spread electron bunches with 120 TW laser pulses guided in a 110 mm-long hydrodynamic optical-field-ionized plasma channel. Our experiments and particle-in-cell simulations show that high-quality electron bunches were only obtained when the drive pulse was closely aligned with the channel axis, and was focused close to the density down ramp formed at the channel entrance. Start-to-end simulations of the channel formation, and electron injection and acceleration show that increasing the channel length to 410 mm would yield 3.65 GeV bunches, with a slice energy spread ∼5×10^{-4}.

Down-regulation of LINC00667 hinders renal tubular epithelial cell apoptosis and fibrosis through miR-34c

Purpose This study aimed to down-regulate LINC00667 and inhibit apoptosis and fibrosis of renal tubular epithelial cells through miR-34c. Methods Altogether, 98 patients with chronic kidney disease treated in our hospital were selected as the study group, and 67 normal people were selected as the control group. Epithelial cells of proximal convoluted tubules in human renal cortex were purchased. TGF-β1 was used to induce fibrosis of HK-2 renal tubular epithelial cells. The expression of LINC00667, miR-34c, type I collagen (Col 1) and type III collagen (Col 3) were detected by qRT-PCR and WB. Results LINC00667 was highly expressed in cancer tissues and HK-2, while miR-34c was poorly expressed. Inhibition of LINC00667 and over-expression of miR-34c could inhibit the proliferation and invasion of chronic kidney disease cells, but increase the apoptosis rate. Down-regulation of LINC00667 could significantly reduce of Col 1 and Col 3 in renal interstitial fibroblasts induced by TGF-β1, while up-regulation of miR-34c could also achieve this effect. Double luciferase report confirmed that there was a targeted regulatory relationship between LINC00667 and miR-34c. Conclusion LINC00667 could reduce the proliferation and invasion of chronic kidney disease cells, increase the apoptosis rate by regulating miR-34c, and improve renal fibrosis (AU)

Down-regulation of LINC00667 hinders renal tubular epithelial cell apoptosis and fibrosis through miR-34c.

PURPOSE: This study aimed to down-regulate LINC00667 and inhibit apoptosis and fibrosis of renal tubular epithelial cells through miR-34c. METHODS: Altogether, 98 patients with chronic kidney disease treated in our hospital were selected as the study group, and 67 normal people were selected as the control group. Epithelial cells of proximal convoluted tubules in human renal cortex were purchased. TGF-ß1 was used to induce fibrosis of HK-2 renal tubular epithelial cells. The expression of LINC00667, miR-34c, type I collagen (Col 1) and type III collagen (Col 3) were detected by qRT-PCR and WB. RESULTS: LINC00667 was highly expressed in cancer tissues and HK-2, while miR-34c was poorly expressed. Inhibition of LINC00667 and over-expression of miR-34c could inhibit the proliferation and invasion of chronic kidney disease cells, but increase the apoptosis rate. Down-regulation of LINC00667 could significantly reduce of Col 1 and Col 3 in renal interstitial fibroblasts induced by TGF-ß1, while up-regulation of miR-34c could also achieve this effect. Double luciferase report confirmed that there was a targeted regulatory relationship between LINC00667 and miR-34c. CONCLUSION: LINC00667 could reduce the proliferation and invasion of chronic kidney disease cells, increase the apoptosis rate by regulating miR-34c, and improve renal fibrosis.

Identification of potential crucial genes associated with vasculogenic mimicry in human osteosarcoma based on gene expression profile.

We previously reported the presence of vasculogenic mimicry (VM) in human osteosarcoma. However, the mechanistic basis of osteosarcoma VM remains unclear. Three hundred eighty-one upregulated differentially expressed genes (DEGs) and 526 downregulated DEGs between human osteosarcoma cell line 143B and HOS cell exposed to Matrigel were screened out by microarray. GO categories such as "cell adhesion", "angiogenesis" were enriched in 143B group. PATHWAY analysis showed enriched TGF-beta, Wnt and VEGF signaling pathway in 143B group. The hub gene ITGA2 in signal-network of DEGs exhibited pro-VM and pro-metastasis effect. Our study provides fundamental data for further studies regarding molecules involved in osteosarcoma VM.

[The relationship between fragmented QRS complex and coronary collateral circulation in patients with chronic total occlusion lesion without prior myocardial infarction].

Objective: To explore the relationship between fragmented QRS complex(fQRS) and coronary collateral circulation(CCC) in patients with chronic total occlusion(CTO)lesion without prior myocardial infarction. Methods: This retrospective study analyzed 238 consecutive patients with CTO lesion in one of the major coronary arteries from May 2014 to October 2015 in our department. Patients were divided into poor CCC group (grade 0 and 1, 58 cases) and good CCC group(grade 2 and 3, 180 cases) based on Rentrop's classification of CCC. The fQRS was defined as the presence of an additional R wave or notching of R or S wave or the presence of fragmentation in two contiguous electrocardiogram leads corresponding to a major coronary artery territory. Multivariate logistic regression was used to analyze the relationship between CCC and fQRS on electrocardiogram. Results: Compared with good CCC group, patients in poor CCC group had older age((65.2±8.9)years old vs. (60.3±10.1) years old, P=0.03), higher plasma glucose ((7.22±3.00) mmol/L vs.(6.31±1.83)mmol/L, P=0.04), and lower left ventricular ejection fraction ((45.2±11.4)% vs. (51.2±13.5)%, P=0.02). None of patients had Rentrop grade 0, the presence of fQRS on ECG in patients with Rentrop grade 1, grade 2, and grade 3 CCC was 69.0% (40/58), 48.6% (35/72) , and 19.4% (21/108), respectively (P<0.01). The presence of fQRS were higher in poor CCC group than in good CCC group (69.0%(40/58)vs. 31.1%(56/180), P<0.01), and number of leads with fQRS were higher in poor CCC group than in good CCC group (3(0, 4)vs.0(0, 3), P<0.01). Multivariate logistic regression analysis demonstrated that poor CCC growth in patients with CTO lesion without prior myocardial infarction was independently related to the presence of fQRS (OR=3.659, 95%CI 1.619-8.217, P<0.01). Conclusion: Poor CCC in patients with CTO lesion without prior myocardial infarction is independently related to the presence of fQRS on electrocardiogram.

Relationship between HBV cccDNA expression in the human ovary and vertical transmission of HBV.

This study aimed to investigate the relationship between hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the ovary and vertical transmission of HBV. HBV DNA and HBV cccDNA were assayed in the ovaries of 33 pregnant women who were positive for HBV DNA. The HBVM (HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) level and the HBV DNA content in peripheral blood of infants were measured. The overall positive rate of HBV DNA and HBV cccDNA in samples was 51·52% (17/33). The intrauterine infection rate of the infants was 12·12% (4/33). When HBV DNA and HBV cccDNA were both positive, the intrauterine infection rate of infants was significantly higher than when they were both negative (P<0·05). Levels of HBV cccDNA and the rate of positive samples were significantly higher in mothers with infants with intrauterine infection than in those without (P<0·01 and P<0·05, respectively). HBV can infect the human ovary and may transmit to the filial generation via the ovum.

Association between interleukin 21 and Graves' disease.

Graves' disease (GD) is an organ-specific autoimmune thyroid disease; 25-50% of GD patients will develop Graves' ophthalmopathy (GO). The etiology of GD and GO may be multifactorial, but the immune response plays a central role. Many studies have reported that IL-21 has crucial roles in autoimmune diseases. We examined whether IL-21 is associated with the development of GD and GO. The serum concentration of IL-21 was tested in 40 primary GD patients, 42 treated GO patients and 24 healthy controls. Our data show that the serum level of IL-21 is associated with the development of GD. We also made an association study with the IL-21 gene polymorphisms rs4833837, rs907715 and rs13143866 in a comparison of 633 patients and 612 healthy controls from the Chinese population. This case-control association study demonstrated that rs907715 SNP is significantly associated with GD, while the rs13143866 A allele is significantly associated with GO. The haplotypes A-G-G and A-A-A were found at higher and lower frequencies, respectively, in GD patients, suggesting a protective role for A-A-A. However, there were no significant differences in the frequencies of these haplotypes between the GO patients and the control group. We found no association between IL-21 gene polymorphisms and the age of GD onset. We conclude that IL-21 is associated with GD and GO.

C6-ceramide synergistically potentiates the anti-tumor effects of histone deacetylase inhibitors via AKT dephosphorylation and α-tubulin hyperacetylation both in vitro and in vivo.

Histone deacetylase inhibitors (HDACIs) have shown promising anti-tumor effects for a variety of malignancies, however, many tumors are reportedly resistant to them. In this study, we made a novel discovery that co-administration of HDACIs (Trichostatin A (TSA) and others) and exogenous cell-permeable short-chain ceramide (C6) results in striking increase in cancer cell death and apoptosis in multiple cancer cells. These events are associated with perturbations in diverse cell signaling pathways, including inactivation of Akt/mTOR and increase in α-tubulin acetylation (both in vivo and in vitro). TSA interacts in a highly synergistic manner with C6-ceramide to disrupt HDAC6/protein phosphatase 1 (PP1)/tubulin complex, to induce α-tubulin hyperacetylation, and to release and activate PP1, which then leads to AKT dephosphorylation and eventually causes cancer cell death. Interestingly, TSA itself results in short-term ceramide accumulation, which as a result of metabolic (glycosylation) removal, does not result in evident increase of cancer cell death. However, adding C6-ceramide led to a very pronounced increase in ceramide level and marked increase in cell death. Importantly, the effective synergistic anti-tumor activity of TSA plus C6-ceramide is also seen in in vivo mice xenograft pancreatic and ovarian cancer models, indicating that this regimen (HDACI plus C6-ceramide) may represent a more effective form of therapy against pancreatic and ovarian carcinoma.

Lattice Boltzmann model for thermal transpiration.

The conventional Navier-Stokes-Fourier equations with no-slip boundary conditions are unable to capture the phenomenon of gas thermal transpiration. While kinetic approaches such as the direct simulation Monte Carlo method and direct solution of the Boltzmann equation can predict thermal transpiration, these methods are often beyond the reach of current computer technology, especially for complex three-dimensional flows. We present a computationally efficient nonequilibrium thermal lattice Boltzmann model for simulating temperature-gradient-induced flows. The good agreement between our model and kinetic approaches demonstrates the capabilities of the proposed lattice Boltzmann method.

Lattice Boltzmann simulation of nonequilibrium effects in oscillatory gas flow.

Accurate evaluation of damping in laterally oscillating microstructures is challenging due to the complex flow behavior. In addition, device fabrication techniques and surface properties will have an important effect on the flow characteristics. Although kinetic approaches such as the direct simulation Monte Carlo (DSMC) method and directly solving the Boltzmann equation can address these challenges, they are beyond the reach of current computer technology for large scale simulation. As the continuum Navier-Stokes equations become invalid for nonequilibrium flows, we take advantage of the computationally efficient lattice Boltzmann method to investigate nonequilibrium oscillating flows. We have analyzed the effects of the Stokes number, Knudsen number, and tangential momentum accommodation coefficient for oscillating Couette flow and Stokes' second problem. Our results are in excellent agreement with DSMC data for Knudsen numbers up to Kn=O(1) and show good agreement for Knudsen numbers as large as 2.5. In addition to increasing the Stokes number, we demonstrate that increasing the Knudsen number or decreasing the accommodation coefficient can also expedite the breakdown of symmetry for oscillating Couette flow. This results in an earlier transition from quasisteady to unsteady flow. Our paper also highlights the deviation in velocity slip between Stokes' second problem and the confined Couette case.

Wavelength-division multiplexing isolation fiber filter and light source using cascaded long-period fiber gratings.

The author has successfully demonstrated a novel all-fiber wavelength-division multiplexing (WDM) isolation filter with more than 20 equally spaced loss peaks within a 60-nm band and a WDM light source with an output of 21 equally spaced wavelengths within 30% amplitude variation.

Biochemistry and pharmacology of 7alpha-substituted androstenediones as aromatase inhibitors.

The inhibition of aromatase, the enzyme responsible for converting androgens to estrogens, is therapeutically useful for the endocrine treatment of hormone-dependent breast cancer. Research by our laboratory has focused on developing competitive and irreversible steroidal aromatase inhibitors, with an emphasis on synthesis and biochemistry of 7alpha-substituted androstenediones. Numerous 7alpha-thiosubstituted androst-4-ene-3,17-diones are potent competitive inhibitors, and several 1,4-diene analogs, such as 7alpha-(4'-aminophenylthio)-androsta-1,4-diene-3,17-di one (7alpha-APTADD), have demonstrated effective enzyme-activated irreversible inhibition of aromatase in microsomal enzyme assays. One focus of current research is to examine the effectiveness and biochemical pharmacology of 7alpha-APTADD in vivo. In the hormone-dependent 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary carcinoma model system, 7alpha-APTADD at a 50 mg/kg/day dose caused an initial decrease in mean tumor volume during the first week, and tumor volume remained unchanged throughout the remaining 5-week treatment period. This agent lowers serum estradiol levels and inhibits ovarian aromatase activity. A second research area has focused on the synthesis of more metabolically stable inhibitors by replacing the thioether linkage at the 7alpha position with a carbon-carbon linkage. Several 7alpha-arylaliphatic androst-4-ene-3,17-diones were synthesized by 1,6-conjugate additions of appropriate organocuprates to a protected androst-4,6-diene or by 1,4-conjugate additions to a seco-A-ring steroid intermediate. These compounds were all potent inhibitors of aromatase with apparent Kis ranging between 13 and 19 nM. Extension of the research on these 7alpha-arylaliphatic androgens includes the introduction of a C1-C2 double bond in the A-ring to provide enzyme-activated irreversible inhibitors. The desired 7alpha-arylaliphatic androsta-1,4-diene-3,17-diones were obtained from their corresponding 7alpha-arylaliphatic androst-4-ene-3,17-diones by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). These inhibitors demonstrated enzyme-mediated inactivation of aromatase with apparent k(inact)s ranging from 4.4 x 10(-4) to 1.90 x 10(-3) s(-1). The best inactivator of the series was 7alpha-phenpropylandrosta-1,4-diene-3,17-dione, which exhibited a T(1/2) of 6.08 min. Aromatase inhibition was also observed in MCF-7 human mammary carcinoma cell cultures and in JAr human choriocarcinoma cell cultures, exhibiting IC50 values of 64-328 nM. The 7alpha-arylaliphatic androgens thus demonstrate potent inhibition of aromatase in both microsomal incubations and in choriocarcinoma cell lines expressing aromatase enzymatic activity. Additionally, the results from these studies provide further evidence for the presence of a hydrophobic binding pocket existing near the 7alpha-position of the steroid in the active site of aromatase. The size of the 7alpha-substituent influences optimal binding of steroidal inhibitors to the active site and affects the extent of enzyme-mediated inactivation observed with androsta-1,4-diene-3,17-dione analogs.

Characterization of polymorphic forms of fluconazole using Fourier transform Raman spectroscopy.

Detailed Fourier transform Raman spectra of fluconazole have been recorded and the main spectral features of fluconazole have been assigned to its vibrational modes. Two different polymorphic forms of fluoconazole were identified in two spectral regions, 150-1700 cm-1 and 2700-3200 cm-1, respectively. The FT-Raman results agree well with those of differential scanning calorimetry and X-ray powder diffractometry. The combination of definiteness with easy sample handling makes FT-Raman spectroscopy a valuable technique for the analysis of polymorphs.

An occupational hygiene survey in a Chinese viscose rayon factory.

The retinopathy (microaneurysm/small dot hemorrhage) is an early and specific biological indicator to quantitatively evaluate the CS2 exposure. The appearance of retinal lesions was observed among Yugoslavian, German and American workers exposed to CS2. However, among Finnish CS2 workers a positive result was not obtained. We suggested a different response to CS2 exposure between two ethnic populations. We had an opportunity to do a cross-sectional medical and occupational hygiene survey in a Chinese rayon staple plant. Cross-sectional medical examinations failed to show any chronic CS2 effects on the Chinese workers.

Biomechanical evaluation of cervical spine instability after multiple level laminectomy.

Four fresh human cervical spine specimens (C2-T1) were tested both intact and with C5-C6 laminectomies to evaluate the biomechanical effects of multiple level laminectomy. The loads applied to the specimens were physiological and clinically relevant motion patterns were simulated. The results showed that C5 vertical displacements increased by 83.33% in axial compression, 168.75% in flexion, 106.09% in extension, and 35.14% in left bending after C5-C6 laminectomies compared with intact specimens. The increased rates of C6 vertical displacements after laminectomy were slightly lower than C5. The anterior horizontal bulging of C5-6 discs increased by 29.69% in axial compression, 13.86% in flexion, 61.79% in extension, and 13.40% in left bending after laminectomy. The rotational angles of whole specimens had an increase of 15% after laminectomy. The strains in the anterior vertebral bodies and posterior laminae near the articular processes of C5 and C6 were increased significantly after laminectomy. The data indicated that multiple level laminectomy can lead to biomechanical instability of the cervical spine.

[Efficacy of ofloxacin in treating typhoid fever].

We studied 75 patients (36 males and 39 females), suffering from typhoid fever. 64 patients were treated with ofloxacin and 11 with amikacin, dosage regimens of the two drugs were 300 mg and 300-400 mg twice daily. Clinical effective rate was 100% with ofloxacin and 36.4% with amikacin. A total of 72 strains of salmonella typhi was isolated from all the patients of both groups. Bacteriological elimination rate was 100% with ofloxacin after treatment. Sensitive rates for S. Typhi isolated was 100% with ofloxacin, norfloxacin and ceftriaxone, 98.6% with amikacin and 20-21.4% with chloramphenicol, ampicillin and sulfamethoxazole Co. There were fewer adverse reactions and better acceptance, one had skin rash and one had gastrointestinal disturbance. In amikacin group, abnormality of urine routine and serum creatinine was observed. Ofloxacin was well absorbed orally. Its high bioavailability, satisfactory therapeutic efficacy excellent tolerability and convenience for use make it a very useful medication in the therapy of typhoid fever resulted from multiresistant strains.

Treatment of typhoid fever with ofloxacin.

Ofloxacin, 300 mg 12-hourly, was given orally to 64 patients with typhoid fever, all with positive blood cultures. Almost 80% of the isolates were resistant to chloramphenicol, ampicillin and co-trimoxazole, but sensitive to ofloxacin and norfloxacin. Fever subsided within five days in most patients (mean 3.2 +/- 1.1), rates of clinical effectiveness and bacteriological cure both being 100%. Thirty patients were followed for 1-3 months after the completion of therapy with no occurrence of relapse.