[HIV/AIDS surveillance in men who have sex with men aged 15-24 based on internet in Fuzhou,2016-2021].

Objective: To analyze HIV/AIDS surveillance data in men who have sex with men (MSM) aged from 15 to 24 years in Fuzhou and understand the HIV infection status in MSM and related factors. Methods: From 2016 to 2021, MSM aged 15-24 years who had oral or anal sex with men in the past 6 months were recruited through internet, and their demographic and behavioral characteristics, HIV antibody positive rate and risk factors were analyzed. Results: From 2016 to 2021, a total of 4 234 MSM aged 15-24 years were surveyed. The proportion of MSM from other provinces increased from 13.00% (85/654) to 23.42% (163/696) (trend χ2=60.23, P<0.001); and the proportion of MSM seeking male partners through internet increased from 93.27% (610/654) to 99.71% (694/696) (trend χ2=65.20, P<0.001); In the last anal sex in the past 6 months, the proportion of MSM using condom decreased from 88.16% (484/549) to 74.11% (415/560) (trend χ2=32.32, P<0.001); and in the past 6 months, the proportion of MSM using condom at each anal sex decreased from 65.76% (361/549) to 55.54% (311/560) (trend χ2 =6.82, P<0.001); The proportion of MSM with HIV antibody testing increased from 5.66% (37/654) to 25.29% (176/696) (trend χ2=98.51, P<0.001). The cumulative HIV antibody positive rate in the MSM was 3.64% (154/4 234), and there was no significant difference in annual HIV antibody positive rate in the MSM (trend χ2=0.50, P=0.453). The HIV antibody positive rate in the MSM with education level of junior high school or below and the MSM living in Fuzhou for 1-2 years showed an upward trend (P<0.05). The results of multivariate logistic regression analysis showed that the risk for HIV infection in the MSM with education level of high school or technical secondary school was 0.54 times higher than that in those with education level of junior high school or below (95%CI: 0.30-0.99), and the risk for HIV infection in the MSM with education level of junior college or below was 0.29 times higher than that in those with education level of junior high school or below (95%CI: 0.17-0.51). The risk for HIV infection in the MSM who lived in Fuzhou for 1-2 years was 0.35 times higher than that in those who lived in Fuzhou for less than 1 year (95%CI: 0.16-0.74), the risk for HIV infection in the MSM who lived in Fuzhou for more than two years was 0.58 times higher than that in those who lived in Fuzhou for less than 1 year (95%CI: 0.37-0.91). The number of MSM using condoms at each anal sex was 0.18 times higher than that in the those never using condoms (95%CI: 0.08-0.42), and the number of the MSM who didn't suffered from sexually transmitted diseases was 0.25 times higher than that in those who suffered from sexually transmitted diseases (95%CI: 0.13-0.50). Conclusions: The MSM aged 15-24 years in Fuzhou have higher risk for HIV infection, and internet based intervention should be strengthened in adolescent MSM without permanent residence and with low education level.

AraR, an L-Arabinose-Responding Transcription Factor, Negatively Regulates Resistance of Mycobacterium smegmatis to Isoniazid.

L-Arabinose is an important component of mycobacterial cell wall. L-Arabinose is involved in the synthesis of arabinogalactan, lipoarabinomannan, and other sugar compounds, which suggests that it can modulate cell wall permeability and drug resistance. However, whether L-arabinose affects mycobacterial antibiotic resistance and the underlying regulatory mechanism remains unclear. In this study, we characterized a new transcription factor of Mycobacterium smegmatis, AraR, that responds to L-arabinose and regulates mycobacterial sensitivity to isoniazid (INH). AraR specifically recognizes two conserved 15-bp motifs within the upstream regulatory region of the arabinose (araR) operon. AraR functions as a transcriptional repressor that negatively regulates araR expression. In contrast to the effect of AraR, overexpression of the araR operon contributes to the mycobacterial INH resistance. L-arabinose acts as an effector and derepresses transcriptional inhibition by AraR. The araR-deficient strain is more resistant to INH than the wild-type strain, whereas the araR-overexpressing strain is more sensitive to INH. Addition of L-arabinose to the medium can significantly increase the resistance to INH of the wild-type strain, but not of the araR knockout strain. Therefore, we identified a new L-arabinose-responding transcription factor and revealed its effect on the bacterial antibiotic resistance. These findings can provide new insights in the regulatory mechanisms mediated by sugar molecules and their relationship with drug resistance in mycobacteria.

Wld(S) protects against peripheral neuropathy and retinopathy in an experimental model of diabetes in mice.

AIMS/HYPOTHESIS: We aimed to evaluate the effect of the mutant Wld(S) (slow Wallerian degeneration; also known as Wld) gene in experimental diabetes on early experimental peripheral diabetic neuropathy and diabetic retinopathy. METHODS: The experiments were performed in four groups of mice: wild-type (WT), streptozotocin (STZ)-induced diabetic WT, C57BL/Wld(S) and STZ-induced diabetic C57BL/Wld(S). In each group, intraperitoneal glucose and insulin tolerance tests were performed; blood glucose, glycated haemoglobin and serum insulin were monitored. These mice were also subjected to the following behavioural tests: grasping test, hot-plate test and von Frey aesthesiometer test. For some animals, sciatic-tibial motor nerve conduction velocity, tail sensory nerve conduction velocity and eye pattern electroretinogram were measured. At the end of the experiments, islets were isolated to detect glucose-stimulated insulin secretion, ATP content and extent of apoptosis. The NAD/NADH ratio in islets and retinas was evaluated. Surviving retinal ganglion cells were estimated by immunohistochemistry. RESULTS: We found that the Wld(S) gene is expressed in islets and protects beta cells against multiple low doses of STZ by increasing the NAD/NADH ratio, maintaining the ATP concentration, and reducing apoptosis. Consistently, significantly higher insulin concentrations, lower blood glucose concentrations, and better glucose tolerance were observed in Wld(S) mice compared with WT mice after STZ treatment. Furthermore, Wld(S) alleviated abnormal sensory responses, nerve conduction, retina dysfunction and reduction of surviving retinal ganglion cells in STZ-induced diabetic models. CONCLUSIONS/INTERPRETATION: We provide the first evidence that expression of the Wld(S) gene decreases beta cell destruction and preserves islet function in STZ-induced diabetes, thus revealing a novel protective strategy for diabetic models.

Tumor suppressor function of BCSC-1 in nasopharyngeal carcinoma.

BCSC-1 is dramatically upregulated in CNE-2L2 human nasopharyngeal carcinoma cells with reduced malignancy (AS cells) and is proposed to be a candidate tumor suppressor gene. We therefore examined the effect of BCSC-1 expression on malignant behaviors of CNE-2L2 cells. Growth in vitro and tumorigenesis in nude mice of wild-type CNE-2L2 cells (W cells) were inhibited by ectopic BCSC-1, and those of AS cells were promoted by BCSC-1 suppression. The tumor suppressor function of BCSC-1 was further confirmed by a study showing that intratumor BCSC-1 injection caused growth suppression of the tumor from W cells inoculated in nude mice. Immunohistochemistry exhibited marked reduction of BCSC-1 expression in 11 of 39 human nasopharyngeal carcinoma specimens. Because BCSC-1 expression was as rich as that in normal cells in the rest of the carcinoma specimens and was poor in CNE-2L2 cells, HNE-1 human nasopharyngeal carcinoma cells with rich BCSC-1 expression were used as a control in the study. No effect of BCSC-1 transfection on growth of the cells was observed. The data suggest that BCSC-1 suppression might play roles in tumorigenesis of some nasopharyngeal carcinomas and that BCSC-1 might be a potential gene therapy target in nasopharyngeal carcinomas with poor BCSC-1 expression. Enhanced aggregation of cells together with increased E-cadherin and alpha-catenin expression and reduced Wnt signaling might be involved in the mechanisms of tumor suppressor function of BCSC-1.

Quantification of trimetazidine in human plasma by liquid chromatography-electrospray ionization mass spectrometry and its application to a bioequivalence study.

A rapid, sensitive and specific liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method has been developed for the quantification of trimetazidine in human plasma. The analyte and the internal standard (pseudoephedrine) were extracted from plasma samples with n-hexane-dichloromethane (1:1, v/v) and analyzed on a C18 column. The chromatographic separation was achieved within 3.5 min using the mobile phase consisting of methanol/0.05% formic acid (80:20, v/v) and the flow rate was 1.0 ml/min. Ion signals m/z 181.0 and 148.0 were measured in the positive mode for trimetazidine and pseudoephedrine, respectively. The calibration curves were linear within the range of 0.4 to approximately 120 ng/ml. The lower limit of quantification (LLOQ) was 0.4 ng/ml with 0.5 ml plasma sample. The intra- and inter-day precisions were lower than 12% in terms of relative standard deviation (RSD). The inter-day relative error (RE) as determined from quality control samples (QCs), ranged from -1.4% to 3.3%. This validated method was successfully applied to the bioequivalent evaluation of two brands of trimetazidine tablets in 20 healthy volunteers.

Effects of 2-hydroxypropyl-beta-cyclodextrin on pharmacokinetics of digoxin in rabbits and humans.

Considering the narrow therapeutic index of digoxin and the low range between the safe and toxic serum concentrations of this drug, to evaluate the relative bioavailability of tablets and oral solution is necessary. The pharmacokinetic properties of digoxin after oral administration of its hydroxypropyl-beta-cyclodextrin (HPCD) inclusion complex to rabbits and human volunteers were investigated in comparison with those of commercially available tablets. The aqueous solubility of digoxin was enhanced by HPCD for about 2000 times at HPCD concentration of 50% (w/v). But in a human bioavailability study no significant difference was observed in the extent of absorption (AUC(0-t)) and Cmax between the two formulations. Time to reach peak was significantly shorter for the solution than for the tablets (p < 0.01). The pharmacokinetic results from the rabbit study were similar to human studies and no significant difference was observed for AUC, Cmax and Tmax. As the bioavailability of both tablets and solution is equivalent HPCD based oral digoxin solution could serve as an alternative to tablets.

Prevalence of human papillomavirus in cervical cancer: a multicenter study in China.

A large-scale epidemiologic survey on the prevalence of different types of human papillomavirus (HPV) in cervical cancer in China is indicated because of the implications for the development of diagnostic probes and vaccines against cervical cancer. A total of 809 cervical cancer specimens were collected from 5 regions in China including Shanghai, Guangzhou, Sichuan, Beijing and Hong Kong. HPV DNA was detected in 83.7% of the specimens. HPV-16 was present in 79.6%, HPV-18 in 7.5%, HPV-52 in 2.6% and HPV-58 in 3.8% of all HPV-positive specimens. The prevalences of HPV-16 and HPV-18 in Hong Kong were 61.7 and 14.8%, respectively, representing a lower HPV-16 and a higher HPV-18 proportion compared with the other regions. HPV-16 remained the most common HPV infection in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). The proportion of HPV-18 infection was significantly higher in AC than in SCC.

[Study on the release mechanism of fenoprofen calcium from hydrophillic sustained-release matrix].

AIM: To study the release mechanism of fenoprofen calcium (FC) from hydroxypropylmethylcellulose (HPMC) matrices. METHODS: The release of FC and the erosion properties of hydrophillic matrices containing HPMC was examined at different paddle speed. The release mechanism of FC was further confirmed by evaluating the n value in Peppas equation. RESULTS: The results indicate that the release of FC and the erosion of matrices exhibit zero order kinetic equation, and it exhibits line relationship between them. CONCLUSION: In the first 40 min, FC mainly released by diffusion and erosion from HPMC matrix, while it was controlled by the rate of tablet erosion after 50 min.

[Pulmonary angitis and granulomatosis].

16 patients of Wegener's granulomatosis, 4 of allergic angiitis and granulomatosis, 3 of lymphomatoid granulomatosis and 1 of necrotizing sarcoid granulomatosis were reported. In this group of different diseases, characteristic pathological manifestations are inflammatory cellular infiltration of vessel wall combined with destruction and necrosis of pulmonary parenchyma. There was little difference in their clinical features. In most of the cases, fever and systemic symptoms related to lung and extrapulmonary organs were present. Correct diagnosis of these diseases is very important, because both the prognosis and therapy are different. As for the prognosis, it ranges from benign (necrotizing sarcoidal granulomatosis) to very malignant (lymphomatoid granulomatosis). The clinical features of each illness were reviewed with emphasis on their histopathologic findings. The therapeutic effect and final outcome were followed.

[Renal tubular acidosis in primary Sjogren's syndrome: study on the immunology and ultrastructure of EBV].

The related antigens of EBV were examined by McAB against Epstein-Barr virus EAp 138. The related antibody of serous EBV VCA and EBNA of Sjogren's syndrome (SS) patients was examined by indirect immunofluorescence and immunoenzyme methods. EBV was found in the tubular epithelial cells by EM and the relationship between EBV and SS was studied. The results showed that (1) Around the nuclei and basement membrane of the proximal tubular epithelial cells there were positively reacting granules but not in the control group. (2) The related antibody of serous EBV VCA and EBNA showed positive reaction, and the highest titre was VCA-IgA 1:80, VCA-IgM 1:40, VCA-IgG 1:320 and EBNA-IgG 1:320 respectively. In addition, mature granules were found in the cytoplasm of the renal tubular epithelial cells.

[Associations between the renal tubular acidosis of primary Sjogren syndrome and the infection of Epstein-Barr virus: a preliminary study].

To explore the possible etiological associations between the infection of Epstein-Barr Virus (EBV) and the occurrence of renal tubular acidosis (RTA) of primary Sjogren's syndrome (SS), renal biopsies from both primary SS with clinical or subclinical RTA and controls were detected by using a monoclonal antibody against EBV early antigen P138 and a 32P-labelled EBV Bam W probe. As a result, cytoplasmic fluorescence staining of epithelial cells with the monoclonal antibody as described above was noted in all the seven renal biopsies from primary SS, and one out of two renal samples among them contained EBV DNA detectable by dot blot hybridization with Bam W probe. Whereas five control renal biopsies were all negative on the same methods of detection. Our study suggested that EBV has been of a lytic fate leading to active replication in the kidneys of patients with RTA of primary SS. Therefore, EBV may play an important role in the renal damage, especially resulting in RTA, of primary SS.

[Analysis of knee arthroscopic findings in rheumatic diseases].

46 patients with knee joint arthritis were subjected to arthroscopic examination. The results were analyzed and its clinical significance was discussed. The postoperative diagnoses were rheumatoid arthritis in 19 cases, Sjögren syndrome in one, seronegative spondyloarthropathy in 4, gouty arthritis in one, tuberculous arthritis in one, pigmented villous nodular synovitis in two, undefined synovitis in 5, osteoarthritis in 8 and nonsynovitis conditions in 5. The most important indication of arthroscopic examination is for differential diagnosis of arthritis of unknown cause, such as rheumatoid arthritis with single knee joint involvement, osteoarthritis with symmetric large and small joints involvement as well as crystal induced arthritis. These conditions showed under arthroscope their special features in synovium both grossly, microscopically and immuno-pathologically. The synovial damage as observed through arthroscopic examination correlated to certain extent with the X-ray film changes of the knee joint, but direct visualization with the former is better than indirect imaging with the latter.

Modulation of rat Kupffer cells on high density lipoprotein receptors on hepatocytes.

The present study found that conditioned media from Kupffer cells preincubated with acetylated LDL or acetylated LDL and zymosan increased the number of HDL receptors on hepatocytes, using the method of conditioned media transfer. This indicated that the transferable factors produced by Kupffer cells modulate HDL receptors on hepatocytes.

Effects of monocyte macrophages stimulation on hepatic lipoprotein receptors.

The first series of in vivo experiments were designed to investigate the effects of monocytic macrophages (MM phi) stimulation by zymosan in cholesterol-fed rats. We found that the MM phi stimulation significantly decreased plasma very-low-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol but not high-density lipoprotein-cholesterol. The hepatic and aortic cholesterol levels were also significantly decreased; meanwhile, the biliary total bile acid and fecal sterol excretion were significantly enhanced. These results were beneficial to the prevention and regression of atherosclerosis. The second series of in vitro experiments led to the discovery that zymosan did not have effect on HDL and LDL binding, uptake and degradation of hepatic parenchymal and nonparenchymal cells isolated from normal rats, but did have significant effects on those isolated from cholesterol-fed rats. The experiments of Kupffer cells modulating hepatocytes also demonstrated that hepatocyte HDL receptor activity was significantly enhanced by conditioned medium from acetylated LDL plus zymosan added to Kupffer cells. Bmax of 125I-labeled HDL specific binding was increased from 237.8 to 295.2 ng/mg cell protein. The Ka value was not affected, indicating that there might be an increment in receptor number, but not receptor affinity. Cholesterol-loaded zymosan-stimulated Kupffer cells might secrete a soluble mediator affecting hepatocyte HDL receptor activity. Zymosan and other MM phi-stimulating reagents are promising in the exploration of a new approach for prevention and treatment of hypercholesterolemia and atherosclerosis.

Clinico-pathological and ultrastructural characteristics of pheochromocytoma. An analysis of 55 cases.

58 tumors of pheochromocytoma from 55 cases were studied clinico-pathologically and electron-microscopically. In this series, males were predominant and the number of left adrenal pheochromocytomas was 1.6 times that of right ones. Extraadrenal pheochromocytomas amounted to 41.4%. All 5 malignant pheochromocytomas in this series arose from extraadrenal paraganglia. Two types of secretory granules corresponding to the epinephrine and norepinephrine granules in the normal adrenal medulla were discerned in all 13 tumors examined under electron microscope. The contents of different types of granules were compared with urinary catecholamine excretion, and no apparent correlation was disclosed. Large amount of "E" granules in tumor cells of some cases might be associated with very low level of urinary epinephrine, while in the other cases, the reverse was true. The amount of catecholamine excreted in urine also bore no relation to the size of the tumor.