Prevalence and trend of gonorrhea in female sex workers and men having sex with men in China: a systematic review and meta-analysis.

OBJECTIVES: This systematic review was conducted to estimate the respective prevalence of gonorrhea among two high-risk populations in China and determine the epidemiological features of gonorrhea in them. STUDY DESIGN: Systematic review. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched to identify studies published between January 1, 1990, and October 31, 2022, with gonorrhea prevalence tested by polymerase chain reaction among female sex workers (FSWs) and men who have sex with men (MSM). Meta-regression and subgroup analyses were used to investigate potential factors of heterogeneity across studies. Trend analysis of prevalence was conducted by the Jonckheere-Terpstra method. RESULTS: We identified 88 prevalence data points from 49 studies in China, with 30,853 participants of FSWs and 5523 participants of MSM. Pooled prevalence of gonorrhea among FSWs and MSM were 6.9% (95% confidence interval: 4.6-9.7%) and 2.5% (95% confidence interval: 1.5-3.7%), respectively. The subgroup analyses showed there were period, regional, and specimen collection methods diversities among FSWs, and diversities of the regions and specimen collection anatomical sites were found among MSM, in which the prevalence of rectum and pharynx was significantly higher than the urethra. A decreasing trend in the prevalence of gonorrhea was seen among FSWs (z = -4.03) from 1999 to 2021, not found for MSM in China. CONCLUSION: The prevalence of gonorrhea is high in two high-risk groups in China, with extragenital infections requiring particular attention. The findings of this study will provide evidence to formulate national policy and guidance for gonorrhea prevention and control.

[Impact of COVID-19 epidemic on syphilis case reporting in China].

Objective: To analyze the impact of COVID-19 epidemic on syphilis case reporting in China, and provide evidence to evaluate the epidemic situation of syphilis and strengthen the prevention and control of syphilis during COVID-19 epidemic. Methods: The data were collected from the National Notifiable Infectious Disease Reporting System of China Information System for Disease Control and Prevention, National STD Management Information System, and the "nCov2019" R package of github website. The changes of reported cases of syphilis before and during COVID-19 epidemic in China were analyzed. Joinpoint regression model was established by using the reported case number of syphilis from 2010 to 2018, the data in 2019 was used for validation, and the number of syphilis cases in 2020 and 2021 was predicted. The impact of COVID-19 epidemic on the number of syphilis cases was evaluated with calculating the percentage error (PE) between actual number and predicted number of syphilis cases reported.The correlation between reported cases of syphilis and COVID-19 was analyzed by Spearman's correlation analysis. The softwares of Joinpoint 4.9.1.0 and SPSS 18.0 were used for statistical analysis. Results: In 2020 and 2021, the reported cases of syphilis in China decreased significantly by 13.32% and 10.41%, respectively, compared with 2019 (before COVID-19 epidemic), and the reported cases of syphilis in 2021 increased by 3.36% compared with 2020. The reported cases of syphilis in 2020 and 2021 decreased by 17.95% and 20.41%, respectively, compared with predicted numbers. From January to March 2020, the reported monthly case number of syphilis was completely negatively correlated with the confirmed case number of COVID-19 (rs=-1.00, P<0.001). In the provinces with different scales of COVID-19 epidemic, there was also a negative correlation between the monthly reported case number of syphilis and confirmed case number of COVID-19 (all P<0.05). Conclusions: In China, the change of reported cases of syphilis was closely associated with COVID-19 epidemic in 2020 and 2021. Due to the influence of COVID-19 epidemic, the number of reported cases of syphilis decreased significantly, but it should not be thought that syphilis incidence will become a decline trend in the future. It is necessary to carefully and scientifically assess the changes in syphilis epidemic.

[Investigation of detection capacities of laboratories in sexually transmitted disease surveillance areas in China].

Objective: To understand the detection capacities of the laboratories in medical institutions in national sexually transmitted disease (STD) surveillance areas in China. Methods: A cross-sectional study was conducted to investigate the applications of STD tests in laboratories of the medical institutions in 105 STD surveillance areas in China, the proportion of each STD test application was calculated and the differences among medical institutions were compared. Results: In 752 medical institutions, the proportions of Treponema pallidum serological test and non-Treponema pallidum serological test applications were 97.5% (733/752) and 91.4% (687/752), respectively. The proportions of gonococcal culture and Chlamydia trachomatis nucleic acid test applications were 48.4% (364/752) and 23.4% (176/752), respectively. The application proportions of all tests for herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) were less than 40%. In medical institutions at provincial, prefectural and county levels, the application proportions of serological tests of Treponema and non-Treponema were all more than 90%, and the application proportions of gonococcal culture were 66.9% (83/124), 46.9% (197/420) and 47.4% (82/173) respectively, the application proportions of Chlamydia trachomatis nucleic acid test were 29.0% (36/124), 25.0% (105/420) and 19.7% (34/173) respectively. The application proportions of syphilis and gonorrhea tests and chlamydia nucleic acid test in public medical institutions were higher than those in private/joint venture medical institutions and higher in dermatological specialized hospitals than those in general hospitals and maternal and child health centers. The application proportions of STD tests in medical institutions in eastern China and central southern China were generally higher than those in other areas, and the lowest was found in northwestern China. Conclusions: Serological tests for syphilis have been carried out widely in medical institutions in all STD surveillance areas in China, but there were insufficient use of tests for gonococcal culture and Chlamydia trachomatis nucleic acid. The application proportions of STD tests vary in medical institutions at different levels and with different types and ownerships, and the development of STD testing is unbalanced in different areas. It is necessary to strengthen the capacity building of gonococcal culture and Chlamydia trachomatis nucleic acid test, and strengthen the capacity building of STD testing in grassroots, private/joint venture medical institutions and those in underdeveloped western areas.

Effects of Crosstalks Between Sumoylation and Phosphorylation in Normal Cellular Physiology and Human Diseases.

Post-translational modifications (PTMs) such as phosphorylation, acetylation, methylation, ubiquitylation, sumoylation are important mechanisms to regulate functions of different proteins. Among various PTMs, phosphorylation, discovered about 60 years ago, is probably the most common modification. In contrast, sumoylation, identified about two decades ago is emerging as a key regulatory mechanism modulating protein functions. Although studies on protein phosphorylation and sumoylation have been extensively reviewed, much less attention has been paid to their cross-talk and their co-regulation of the same protein target. Here we summarize various examples of the cross-talks between protein phosphorylation and sumoylation, and discuss their functions in regulating normal physiology and pathogenesis.

Regulation of Eye Development by Protein Serine/Threonine Phosphatases-1 and -2A.

The protein serine/threonine phosphatases-1 and -2A are major cellular phosphatases, playing a fundamental role in organisms from prokaryotes to eukaryotes. They contribute to 90% dephosphorylation in eukaryote proteins. In the eye, both phosphatases are highly expressed and display important functions in regulating normal eye development. Moreover, they are implicated in pathogenesis through modulation of stress-induced apoptosis. Here we review the recent progresses on these aspects.

A Cu/Zn superoxide dismutase from Jatropha curcas enhances salt tolerance of Arabidopsis thaliana.

Superoxide dismutases (SODs) are involved in protecting plants against diverse biotic and abiotic stresses. In the present study, a novel Cu/Zn-SOD gene (JcCu/Zn-SOD) was cloned from Jatropha curcas L. Quantitative reverse transcription-polymerase chain reaction analysis revealed that JcCu/Zn-SOD is constitutively expressed in different tissues of J. curcas and induced under NaCl treatment. To characterize the function of this gene with respect to salt tolerance, the construct p35S:JcCu/Zn-SOD was developed and transformed into Arabidopsis using Agrobacterium-mediated transformation. Compared with wild-type, transgenic plants over-expressing JcCu/Zn-SOD showed enhanced tolerance to salt stress during germination, seedling establishment, and growth in terms of longer root, larger rosette area, and a larger number of leaves in addition to higher SOD activity levels under NaCl stress. In addition, over-expression of JcCu/Zn-SOD resulted in lower monodialdehyde content in transgenic Arabidopsis compared to wild-type plants under the same NaCl stress. Therefore, JcCu/Zn-SOD can increase a plant salt stress tolerance potentially by reducing oxidant injury.

The tumor suppressor, p53 regulates the γA-crystallin gene during mouse lens development.

The tumor suppressor, p53 regulates a large number of target genes to control cell proliferation and apoptosis. In addition, it is also implicated in the regulation of cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates several genes including c-Maf and Prox1, two important transcription factors for lens differentiation, and αA and ßA3/A1, the lens differentiation markers. In the present study, we present evidence to show that the γA-crystallin gene distal promoter and the first intron also contain p53 binding sites and are capable of mediating p53 control during mouse lens development. First, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from human lens epithelial cells (HLE) directly binds to the p53 binding sites present in the γA-crystallin gene. Second, the exogenous wild type p53 induces the dose-dependent expression of the luciferase reporter gene driven by the basic promoter containing the γA-crystallin gene p53 binding site. In contrast, the exogenous dominant negative mutant p53 causes a dose-dependent inhibition of the same promoter. Third, ChIP assays revealed that p53 binds to the γA-crystallin gene promoter in vivo. Finally, in the p53 knockout mouse lenses, the expression level of the γAcrystallin gene was found attenuated in comparison with that in the wild type mouse lenses. Together, our results reveal that p53 regulates γA-crystallin gene expression during mouse lens development. Thus, p53 directly regulates all 3 types of crystallin genes to control lens differentiation.

Indazole inhibition of cystic fibrosis transmembrane conductance regulator Cl(-) channels in rat epididymal epithelial cells.

Previous studies have shown that two indazole compounds, lonidamine [1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid] and its analogue AF2785 [(1-(2,4-dichlorobenzyl)-indazol-3-acrylic acid], suppress fertility in male rats. We also found that these compounds inhibit the cystic fibrosis transmembrane conductance regulator chloride (CFTR-Cl(-)) current in epididymal epithelial cells. To further investigate how lonidamine and AF2785 inhibit the current, we used a spectral analysis protocol to study whole-cell CFTR current variance. Application of lonidamine or AF2785 to the extracellular membrane of rat epididymal epithelial cells introduced a new component to the whole-cell current variance. Spectral analysis of this variance suggested a block at a rate of 3.68 micro mol(-1)/sec(-1) and an off rate of 69.01 sec(-1) for lonidamine, and an on rate of 3.27 micro mol(-1)/sec(-1) and an off rate of 108 sec(-1) for AF2785. Single CFTR-Cl(-) channel activity using excised inside-out membrane patches from rat epididymal epithelial cells revealed that addition of lonidamine to the intracellular solution caused a flickery block (a reduction in channel-open time) at lower concentration (10 micro M) without any effect on open channel probability or single-channel current amplitude. At higher concentrations (50 and 100 micro M), lonidamine showed a flickery block and a decrease in open-channel probability. The flickery block by lonidamine was both voltage-dependent and concentration-dependent. These results suggest that lonidamine and AF2785, which are open-channel blockers of CFTR at low concentrations, also affect CFTR gating at high concentrations. We conclude that these indazole compounds provide new pharmacological tools for the investigation of CFTR. By virtue of their interference with reproductive processes, these drugs have the potential for being developed into novel male contraceptives.

A BK(Ca) to K(v) switch during spermatogenesis in the rat seminiferous tubules.

Spermatogenesis is a complex cellular event during which the diploid germ cells differentiate and divide by mitosis and meiosis at specific time points along the spermatogenic cycle to generate the haploid spermatozoa. For this complex event to go in an orderly manner, cell differentiation and division must be precisely controlled by signals arising from within and outside the seminiferous tubules. Changes in the membrane potential of the germ cells are likely to be an important part of the signaling mechanism. We have applied the whole-cell patch clamp technique to identify and characterize ion channels in different spermatogenic cells from immature and mature rat testes fractionated by discontinuous Percoll gradient. A voltage- and Ca(2+)- dependent, outwardly rectifying current with gating and pharmacologic properties resembling the large conductance K(+) channels (BK(Ca)) was recorded from the spermatogonia and primary spermatocytes. Another voltage-dependent, outwardly rectifying current that was sensitive to 4-aminopyridine, a K(v) channel blocker, was detected in spermatocytes and early spermatids. This current is likely caused by the smaller conductance, voltage-sensitive K(+) channels (K(v)). In some spermatogonia, both the BK(Ca) channels and the K(v) channels could be simultaneously detected in the same cell. It appears that during the course of spermatogenesis, there is up-regulation of K(v) but down-regulation of BK(Ca). Reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemistry further confirmed the differential expression of the ion channels in different spermatogenic cells. We conclude that these ion channels may play an important role in the control of spermatogenesis.

Expression of the cystic fibrosis transmembrane conductance regulator in rat spermatids: implication for the site of action of antispermatogenic agents.

To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) is functionally expressed in the testis, we subjected spermatogenic cells from rat testes to analysis of CFTR mRNA, protein and channel activity. CFTR mRNA was detected in the testes of mature but not immature rats using reverse transcription-polymerase chain reaction analysis. Western blot analysis performed with a CFTR specific antibody revealed immunoreactivity in the membrane extract of spermatogenic cells. Immunohistochemical studies localized CFTR in round and elongated spermatids, but not in the fully developed spermatozoa. Using a whole-cell patch clamp technique, we recorded an inward current activated by intracellular cAMP (100 micromol/l) in round spermatids. The current displayed a linear I / V relationship and was inhibited by diphenylamine-2-carboxylate (DPC), a chloride channel blocker. Transfection of the rat germ cell CFTR cDNA into human embryonic kidney (HEK) 293 cells caused the expression of a cAMP-activated chloride current with CFTR characteristics. The current was completely blocked by the antispermatogenic agents 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid, lonidamine (500 micromol/l) and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid, AF2785 (250 micromol/l). These results taken together provide evidence that CFTR is differentially expressed in spermatids during spermiogenesis. We speculate that CFTR may interact with aquaporin to bring about cytoplasmic volume contraction which is an essential feature of spermiogenesis.

Expression of cystic fibrosis transmembrane conductance regulator in rat efferent duct epithelium.

The expression of cystic fibrosis transmembrane conductance regulator (CFTR) was studied in rat efferent ducts. Under whole-cell patch-clamp condition, efferent duct cells responded to intracellular cAMP with a rise in inward current. The cAMP-activated current exhibited a linear I-V relationship and time- and voltage-independent characteristics. The current was inhibited by the Cl(-) channel blocker diphenylamine 2,2'-dicarboxylic acid (DPC) in a voltage-dependent manner and reversed at 24 +/- 0.5 mV, close to the equilibrium potential for Cl(-) (30 mV), suggesting that the current was Cl(-) selective. The cAMP-activated current displayed a permeability sequence of Br(-) > Cl(-) > I(-). Short-circuit current measurement in cultured rat efferent duct epithelia also revealed a cAMP-activated inward current inhibitable by DPC. These electrophysiological properties of the cAMP-activated Cl(-) conductance in the efferent duct were consistent with those reported for CFTR. In support of the functional studies, reverse transcription polymerase chain reaction revealed the presence of CFTR message in cultured efferent duct epithelium. Immunohistochemical studies in intact rats also demonstrated CFTR protein at the apical membrane of the principal cells of efferent duct. CFTR may play a role in modulating fluid transport in the efferent duct.

Lonidamine and analogue AF2785 block the cyclic adenosine 3', 5'-monophosphate-activated chloride current and chloride secretion in the rat epididymis.

The cystic fibrosis transmembrane conductance regulator (CFTR) or the small conductance cAMP-activated chloride channel encoded by the CFTR gene has been shown to play an important role in the formation of the epididymal fluid microenvironment. Mutation of the gene has led to widespread effects on male reproduction. Like other ion channels, CFTR is amenable to pharmacological intervention. Blocking CFTR in the epididymis could in principle lead to disruption of the epididymal fluid environment. We report for the first time two indazole compounds: lonidamine and 1-(2, 4-dichlorobenzyl)-indazole-3-acrylic acid (AF2785) are potent blockers of CFTR in the epididymis. When added to the external solution under whole-cell patch clamp conditions, AF2785 and lonidamine inhibited the cAMP-activated chloride current in rat epididymal cells with apparent IC(50) values of 170.6 and 631.5 microM, respectively; by comparison the IC(50) value for diphenylamine-2-carboxylate, a well-known chloride channel blocker was 1294 microM. In cultured rat epididymal epithelia mounted in a Ussing chamber, AF2785 and lonidamine inhibited the cAMP-stimulated short-circuit current (a measure of chloride secretion) when added to the apical bathing solution with potency greater than any known chloride channel studied. It is proposed that in view of the important role CFTR plays in male reproduction, further study with these and other new indazole compounds for their CFTR blocking actions can provide a new avenue of research into the development of novel male contraceptives.

Epidemiologic trends of sexually transmitted diseases in China.

OBJECTIVE: To describe the current epidemiology of sexually transmitted diseases (STDs), we analyzed the time trends in distribution of reported cases of STDs in China from 1989 to 1998. STUDY DESIGN: Based on the computerized database of the National System of STD Surveillance, a retrospective study of STD cases reported from 1989 to 1998 was carried out. RESULTS: From 1989 to 1998, STD incidence increased significantly in men and women and demonstrated nonlinear growth trends, with the exception of gonorrhea incidence. Between 1990 and 1998, the incidence increased more in females (4.20 times) than that in males (3.79 times). Syphilis incidence increased approximately 20 times during this period at an average annual rate of 52.7%. Gonorrhea incidence increased 2.6 times during this period at an average annual rate of 11.4%, which reached a plateau from 1994 to 1997. Extramarital transmission as source of STD infection has significantly increased from 1995 to 1998. CONCLUSION: The incidence of STDs has continued to increase in China from 1989 to 1998. The epidemic patterns are different from rates in developed counties in which behavior interventions have been successfully implemented, suggesting the need for active behavioral-intervention programs in China.

PIP: To describe the current epidemiology of sexually transmitted diseases (STDs), the authors analyzed the time trends in distribution of reported cases of STDs in China from 1989 to 1998. Based on the computerized database of the National System of STD Surveillance, a retrospective study of STD cases reported from 1989 to 1998 was carried out. From 1989 to 1998, STD incidence increased significantly in men and women and demonstrated nonlinear growth trends, with the exception of gonorrhea incidence. Between 1990 and 1998, the incidence increased more in females (4.20 times) than that in males (3.79 times). Syphilis incidence increased approximately 20 times during this period at an average annual rate of 52.7%. Gonorrhea incidence increased 2.6 times during this period at an average annual rate of 11.4%, which reached a plateau from 1994 to 1997. Extramarital transmission as source of STD infection significantly increased from 1995 to 1998. The incidence of STDs continued to increase in China from 1989 to 1998. The epidemic patterns are different from rates in developed counties in which behavior interventions have been successfully implemented, suggesting the need for active behavioral-intervention programs in China.

Characterization of Lonidamine and AF2785 blockade of the cyclic AMP-activated chloride current in rat epididymal cells.

It has been shown previously that the antifertility agents Lonidamine and its analogue AF2785, [1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid] are potent inhibitors of the cAMP-activated chloride channel (CFTR) in rat epididymal cells. In this study, we further characterized the blocking actions of these two compounds and compared them with the known chloride channel blocker diphenylamine-2-carboxylate (DPC). Results show that the order of potency in blocking the cAMP-activated current is AF2785 > Lonidamine > DPC. All three compounds shared similar blocking characteristics. Firstly, their blockade of the current exhibited voltage dependence; all three agents blocked the current more markedly at negative than at positive membrane potentials. Secondly, they blocked the channels from the outside of the cell. Thirdly, their blocking efficacies were maximal at low extracellular pH. Lastly, the time course of the block by AF2785 and DPC appeared to be more rapid than that of Lonidamine. It is hoped that further studies with other indazole compounds will add knowledge to the physiology and pharmacology of CFTR in the epididymis. Such information will be of great importance to our quest for novel male contraceptives.

Interference with the formation of the epididymal microenvironment--a new strategy for male contraception?

The cystic fibrosis transmembrane conductance regulator (CFTR) or the small conductance cAMP-activated chloride channel encoded by the CFTR gene has been shown to play an important role in the formation of the epididymal fluid microenvironment. Recent work in our laboratory has shown that this protein is also expressed by developing germ cells indicating a role of this protein in spermatogenesis. In view of the fact that the CFTR gene has a far reaching and widespread effect on human reproduction, understanding the role of CFTR in the male reproductive tissues and its intervention by pharmacological agents can open a new avenue of research into the development of novel male contraceptives.

Kinetic models for astaxanthin production by high cell density mixotrophic culture of the microalga Haematococcus pluvialis.

High cell density cultivation of Haematococcus pluvialis for astaxanthin production was carried out in batch and fed-batch modes in 3.7-L bioreactors with stepwise increased light intensity control mode. A high cell density of 2.65 g x L(-1) (batch culture) or 2.74 g x L(-1) (fed-batch culture) was obtained, and total astaxanthin production in the fed-batch culture (64.36 mg x L(-1)) was about 20.5% higher than in the batch culture (53.43 mg x L(-1)). An unstructured kinetic model to describe the microalga culture system including cell growth, astaxanthin formation, as well as sodium acetate consumption was proposed. Good agreement was found between the model predictions and experimental data. The models demonstrated that the optimal light intensity for mixotrophic growth of H. pluvialis in batch or fed-batch cultures in a 3.7-L bioreactor was 90-360 micromol x m(-2) x s(-1), and that the stepwise increased light intensity mode could be replaced by a constant light intensity mode.