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A meta-analysis was conducted comprehensively to investigate the impact of evidence-based nursing (EBN) interventions on pressure injury (PI) in the intensive care unit (ICU) patients. Computer searches were performed, from databases inception to November 2023, in Wanfang, PubMed, China National Knowledge Infrastructure, Google Scholar, Embase, and Cochrane Library for randomized controlled trials (RCTs) on the application of EBN interventions in ICU patients. Two independent researchers conducted screenings of the literature, extracted data, and carried out quality evaluations. Stata 17.0 software was employed for data analysis. Overall, 25 RCTs, involving 2494 ICU patients, were included. It was found that compared to conventional care methods, the implementation of EBN interventions in ICU patients markedly decreased the occurrence of PI (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.17-0.30, p < 0.001), delayed the onset time of pressure ulcers (standardized mean difference [SMD]: -1.61, 95% CI: -2.00 to -1.22, p < 0.001), and also improved nursing satisfaction (OR: 1.18, 95% CI: 1.14-1.23, p < 0.001). Our findings suggest the implementation of EBN interventions in the care of PI in ICU patients is highly valuable, can reduce the occurrence of PI, can delay the time of appearance, and is associated with relatively higher nursing satisfaction, making it worthy of promotion., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis., (© 2023. The Author(s).)

Worldwide, termites are one of few social insects. In this research, the stages of embryonic development in the parthenogenetic and sexual eggs of Reticulitermes aculabialis and R. flaviceps were observed and described. In R. flaviceps , the egg development of the FF and FM groups happened during the early phases of development, whereas in R. aculabialis , this appeared mainly during the late phase of development. The variance in the number of micropyles between the R. flaviceps FF colony type and the R. aculabialis FF colony type was statistically significant. Five stages of egg development were found in both types of R. aculabialis but only the sexual eggs of R. flaviceps. In R. flaviceps , 86% of the parthenogenetic eggs stopped growing during the blastoderm development, with the yolk cell assembling frequently in the center of the egg. According to the results of the single-cell transcriptome sequencing, we investigated the egg-to-larval expression level of genes ( pka , map2k1 , mapk1/3 , hgk , mkp , and pax6 ) and indicated that the levels of essential gene expression in RaFF were considerably higher than in RfFF ( p < 0.05). We also discovered that the oocyte cleavage rate in the FF colony type was considerably lower in R. flaviceps compared to R. aculabialis , which gave rise to a smaller number of mature oocytes in R. flaviceps . During ovulation in both species, oocytes underwent activation and one or two cleavage events, but the development of unfertilized eggs ceased in R. flaviceps . It was shown that termite oocyte and embryonic development were heavily influenced by genes with significant expressions. Results from the databases KEGG, COG, and GO unigenes revealed the control of numerous biological processes. This study is the first to complete a database of parthenogenetic and sexual eggs of R. flaviceps and R. aculabialis .

Background: In the neurogenic niches of the adult hippocampus, new functional neurons are continuously generated throughout life, and generation of these neurons has been implicated in learning and memory. Astrocytes, as components of the neurogenic niches, are critical in the regulation of adult hippocampal neurogenesis (AHN). However, little is known about how astrocytes receive and respond to extrinsic cues to regulate AHN., Methods: By using a transgenic strategy to conditionally delete astrocytic CRHM1 in mice and AAV (adeno-associated virus)-mediated overexpression of astrocytic CHRM1 specifically in the hippocampal dentate gyrus, we systematically investigated the role of astrocytic CHRM1 in the regulation of AHN and the underlying mechanisms using the combined approaches of immunohistochemistry, retrovirus labeling, electrophysiology, primary astrocyte cultures, immunoblotting, and behavioral assays., Results: We report that genetic ablation of CHRM1 in astrocytes led to defects in neural stem cell survival, neuronal differentiation, and maturation and integration of newborn neurons in the dentate gyrus. Astrocytic CHRM1-mediated modulation of AHN was mediated by BDNF (brain-derived neurotrophic factor) signaling. Furthermore, CHRM1 ablation in astrocytes impaired contextual fear memory. These impairments in both AHN and memory were rescued by overexpression of astrocytic CHRM1 in the dentate gyrus., Conclusions: Our findings reveal a critical role for astrocytes in mediating cholinergic regulation of AHN and memory through CHRM1., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The longevity phenomenon is entirely controlled by the insulin signaling pathway (IIS-pathway). Both vertebrates and invertebrates have IIS-pathways that are comparable to one another, though no one has previously described de novo transcriptome assembly of IIS-pathway-associated genes in termites. In this research, we analyzed the transcriptomes of both reproductive (primary kings “PK” and queens “PQ”, secondary worker reproductive kings “SWRK” and queens “SWRQ”) and non-reproductive (male “WM” and female “WF” workers) castes of the subterranean termite Reticulitermes chinensis. The goal was to identify the genes responsible for longevity in the reproductive and non-reproductive castes. Through transcriptome analysis, we annotated 103,589,264 sequence reads and 184,436 (7G) unigenes were assembled, GC performance was measured at 43.02%, and 64,046 sequences were reported as CDs sequences. Of which 35 IIS-pathway-associated genes were identified, among 35 genes, we focused on the phosphoinositide-dependent kinase-1 (Pdk1), protein kinase B2 (akt2-a), tuberous sclerosis-2 (Tsc2), mammalian target of rapamycin (mTOR), eukaryotic translation initiation factor 4E (EIF4E) and ribosomal protein S6 (RPS6) genes. Previously these genes (Pdk1, akt2-a, mTOR, EIF4E, and RPS6) were investigated in various organisms, that regulate physiological effects, growth factors, protein translation, cell survival, proliferation, protein synthesis, cell metabolism and survival, autophagy, fecundity rate, egg size, and follicle number, although the critical reason for longevity is still unclear in the termite castes. However, based on transcriptome profiling, the IIS-pathway-associated genes could prolong the reproductive caste lifespan and health span. Therefore, the transcriptomic shreds of evidence related to IIS-pathway genes provide new insights into the maintenance and relationships between biomolecular homeostasis and remarkable longevity. Finally, we propose a strategy for future research to decrypt the hidden costs associated with termite aging in reproductive and non-reproductive castes.

Objectives: The objective of this study is to compare the epidemiologic, clinical, laboratory, and imaging features, and outcomes in patients with Cryptococcus gattii meningitis (CGM) and Cryptococcus neoformans meningitis (CNM)., Methods: We performed a retrospective study of HIV-negative patients with CGM and CNM (2015-2021) distinguished by metagenomic next-generation sequencing in cerebrospinal fluid in South China., Results: A total of 81 patients (17 CGM, 64 CNM) were enrolled (72.8% male, median age 49 years, range 21-77 years), and CGM patients were younger (median, 43 vs 53 years, p = .005). Of 17 CGM, VGI and VGII accounted for 70.6% and 29.4%, respectively. CGM patients had less underlying diseases (7/17 [41.2%] vs 48/64 [75%], p = .018) and focal neurologic deficit (3/17 [17.6%] vs 35/64 [54.7%], p = .022), had higher intracranial pressure (15/17 [88.2%] vs 25/64 [39.1%], p = .002), more meningeal enhancement (14/17 [82.4%] vs 32/64 [50%], p = .034), less parenchymal involvement (median, 1 vs 3, p = .018), more lung cryptococcomas (6/12 [50%] vs 6/47 [12.8%], p = .014), faster CSF fungal clearance (p = .004), less complications (median, 1 vs 3, p < .001), and more favourable outcomes (16/17 [94.1%] vs 41/64 [64.1%], p = .035)., Conclusions: This study demonstrated that species identification helps to guide therapy and predict outcomes., (© 2022 Wiley-VCH GmbH.)

Background: Cryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome., Case Presentation: A 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions., Conclusions: This case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases. Clinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging., (© 2022. The Author(s).)

Depression is a common but serious mental disorder and can be caused by the side effects of medications. Evidence from abundant clinical case reports and experimental animal models has revealed the association between the classic anti-acne drug 13-cis-retinoic acid (13-cis-RA) and depressive symptoms. However, direct experimental evidence of this mechanism and information on appropriate therapeutic rescue strategies are lacking. Herein, our data revealed that chronic administration of 13-cis-RA to adolescent mice induced depression-like behavior but not anxiety-like behavior. We next demonstrated that chronic 13-cis-RA application increased neural activity in the dentate gyrus (DG) using c-Fos immunostaining, which may be critically involved in some aspects of depression-like behavior. Therefore, we assessed electrophysiological functions by obtaining whole-cell patch-clamp recordings of dentate granule cells (DGCs), which revealed that chronic 13-cis-RA treatment shifted the excitatory-inhibitory balance toward excitation and increased intrinsic excitability. Furthermore, a pharmacogenetic approach was performed to repeatedly silence DGCs, and this manipulation could rescue depression-like behavior in chronically 13-cis-RA-treated mice, suggesting DGCs as a potential cellular target for the direct alleviation of 13-cis-RA-induced depression., (© 2021. The Author(s).)

Non-small-cell lung carcinoma (NSCLC) accounts for approximately 80% of lung cancers with a high metastatic potential. Elucidating the mechanism of NSCLC metastasis will provide new promising targets for NSCLC therapy and benefit its prognosis. Plasmacytoma variant translocation 1 (PVT1) has been proven to be overexpressed in NSCLC. Although the oncogenic role of PVT1 in NSCLC has been reported, its mechanism remains unclear. Here, we verified that the knockdown of PVT1 inhibited NSCLC cell migration and invasion, and that its inhibitory role on A549 cells and H1299 cells was antagonized by interleukin-6 (IL-6) treatment. The results revealed that PVT1 regulates IL-6 by sponging miR-760 and identified the binding site of miR-760 in the 3'-UTR of IL-6. In conclusion, a new mechanism was revealed, wherein PVT1 regulates NSCLC cell migration and invasion via miR-760/IL-6, suggesting PVT1/miR-760/IL-6 as promising prognostic biomarkers and therapeutic targets for NSCLC metastasis., (Copyright © 2020. Published by Elsevier Ltd.)

Insulin is a protein hormone that controls the metabolism of sugar, fat and protein via signal transduction in cells, influencing growth and developmental processes such as reproduction and ageing. From nematodes to fruit flies, rodents and other animals, glucose signalling mechanisms are highly conserved. Reproductive termites (queens and kings) exhibit an extraordinarily long lifespan relative to non-reproductive individuals such as workers, despite being generated from the same genome, thus providing a unique model for the investigation of longevity. The key reason for this molecular mechanism, however, remains unclear. To clarify the molecular mechanism underlying this phenomenon, we sequenced the transcriptomes of the primary kings (PKs), primary queens (PQs), male (WMs) and female (WFs) workers of the lower subterranean termite Reticulitermes chinensis. We performed RNA sequencing and identified 33 insulin signalling pathway-related genes in R. chinensis. RT-qPCR analyses revealed that EIF4E and RPS6 genes were highly expressed in WMs and WFs workers, while mTOR expression was lower in PKs and PQs than in WMs and WFs. PQs and PKs exhibited lower expression of akt2-a than female workers. As the highly conserved insulin signalling pathway can significantly prolong the healthspan and lifespan, so we infer that the insulin signalling pathway regulates ageing in the subterranean termite R. chinensis. Further studies are recommended to reveal the biological function of insulin signalling pathway-related genes in the survival of termites to provide new insights into biomolecular homeostasis maintenance and its relationship to remarkable longevity.

Objective: To analyze Mycoplasma genitalium (MG) infection among the patients attending the clinic of sexually transmitted diseases (STD) in Nanjing., Methods: Urethral and cervical swabs were collected from 2 753 patients (2 161 males and 592 females) who first sought medical care at our STD Clinic from November 2015 to December 2017. The patients ranged in age from 18 to 67 years (［37.55 ± 10.37］ yr), divided into six age groups: ≤20, 21－30, 31－40, 41－50, 51－60, and >60 yr. The samples were examined for MG infection by simultaneous amplification and testing, Chlamydia trachomatis (CT) by quantitative real-time PCR, Neisseria gonorrhoeae (NG), Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) with the Thayer-Martin medium, and the count of polymorphonuclear leukocytes (PMNL) by microscopy with Methylene blue stain., Results: Among the 2 753 samples, 219 (7.95%), including 176 males (8.14%) and 43 females (7.26%), were found positive for MG, with no statistically significant differences between the male and female groups (χ2 = 0.492, P = 0.483). The MG infection rates in the male and female groups were 6.67% vs 12.12% in the ≤20-year-olds, 8.44% vs 8.64% in the 21－30-year-olds, 7.63% vs 6.19% in the 31－40-year-olds, 10% vs 4.72% in the 41－50-year-olds, 5.64% vs 0 in the 51－60-year-olds, and 8.33% vs 0 in the >60-year-olds, with no statistically significant differences among the age groups (χ2 = 4.76, P = 0.446), or in the males (χ2 = 7.240, P = 0.200) or females (χ2 = 6.718, P = 0.076). The incidence rate of MG simple infection was markedly higher in the males than in the females (62.30% ［76/122］ vs 36.84% ［14/38］, χ2 = 7.041, P < 0.01). MG infection was found in combination with one or more pathogens like NG, CT, UU and MH, with MG+UU as the most common co-infection (21.31% ［26/122］ in males and 31.85% ［12/38］ in females). Of the 76 male patients with MG simple infection, 30 (39.47%) had ≥5 PMNLs per high-power field, and 66 (86.84%) showed symptoms of urethritis., Conclusions: MG infection was found in both the symptomatic and asymptomatic patients attending the STD clinic in Nanjing, with no significant difference in the incidence rate between males and females. A higher rate of MG simple infection was observed in the males than in the females, most of the male patients with symptoms of urethritis and urethral PMNLs.

Sialylation of lacto- N -neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for monoclonal antibody (MAb) 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho- N -acetylneuraminic acid (CMP-Neu5Ac)-containing medium enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOSs of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and an MS11 mutant with lactose only from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6 linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. Strain 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with MAb 2C7; MAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. MAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose in vivo Our findings reinforce the candidacy of the 2C7 epitope as a vaccine antigen and MAb 2C7 as an immunotherapeutic antibody., (Copyright © 2018 American Society for Microbiology.)

Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections and in vitro -grown N. gonorrhoeae isolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions, while 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic-resistant genotypes and in vitro phenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programed genotypically and also driven by sex-specific environments. Collectively, our results indicate that distinct N. gonorrhoeae gene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex-specific differences in expression of antibiotic resistance genes. IMPORTANCE Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis of N. gonorrhoeae in subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance of N. gonorrhoeae is high and increasing. We found that N. gonorrhoeae transcriptional responses to infection differed in genital specimens taken from men and women, particularly antibiotic resistance gene expression, which was increased in men. These sex-specific findings may provide a new approach to guide therapeutic interventions and preventive measures that are also sex specific while providing additional insight to address antimicrobial resistance of N. gonorrhoeae ., (Copyright © 2018 Nudel et al.)

Neisseria gonorrhoeae (NG), as a pathogen of gonorrhea, is strictly limited to growth on the human host. In case of gonococcal infection, the body may recruit such inflammatory cells as neutrophils to resist the invasion of NG or initiate its adaptive immune response by antigen presentation to eliminate the pathogen. However, a series of immune escape mechanisms of NG make it difficult to clear up the infection. In the innate immune system, NG can not only secrete thermonuclease to degrade neutrophile granulocytes, inhibit respiratory burst to resist killing by neutrophils, activate NLRP3 to prompt the pyronecrosis of inflammatory cells, but also regulate the differentiation of macrophages to reduce the inflammatory response, combine with factor H to evade complement-mediated killing. NG infection can hardly give rise to effective adaptive immune response and immune memory, but can promote TGF-β production to inhibit Th1/Th2-mediated adaptive immune response, bind to CEACAM1 on the B cell surface to promote apoptosis in B cells, and combine with CEACAM1 on the T cell surface to inhibit helper T cell proliferation, which makes it difficult for B cells to produce high-affinity specific antibodies. With the increasing drug-resistance of NG, immunological studies may play a significant role in the development of novel therapies and effective vaccines against the infection.

Azithromycin resistance (AZM-R) of Neisseria gonorrhoeae is emerging as a clinical and public health challenge. We determined molecular characteristics of recent AZM-R Nanjing gonococcal isolates and tracked the emergence of AZM-R isolates in eastern Chinese cities in recent years. A total of 384 N. gonorrhoeae isolates from Nanjing collected from 2013 to 2014 were tested for susceptibility to AZM and six additional antibiotics; all AZM-R strains were characterized genetically for resistance determinants by sequencing and were genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST). Among the 384 isolates, 124 (32.3%) were AZM-R. High-level resistance (MIC, ≥256 mg/liter) was present in 10.4% (40/384) of isolates, all of which possessed the A2143G mutation in all four 23S rRNA alleles. Low- to mid-level resistance (MIC, 1 to 64 mg/liter) was present in 21.9% (84/384) of isolates, 59.5% of which possessed the C2599T mutation in all four 23S rRNA alleles. The 124 AZM-R isolates were distributed in 71 different NG-MAST sequence types (STs). ST1866 was the most prevalent type in high-level AZM-R (HL-AZM-R) isolates (45% [18/40]). This study, together with previous reports, revealed that the prevalence of AZM-R in N. gonorrhoeae isolates in certain eastern Chinese cities has risen >4-fold (7% to 32%) from 2008 to 2014. The principal mechanisms of AZM resistance in recent Nanjing isolates were A2143G mutations (high-level resistance) and C2599T mutations (low- to mid-level resistance) in the 23S rRNA alleles. Characterization of NG-MAST STs and phylogenetic analysis indicated the genetic diversity of N. gonorrhoeae in Nanjing; however, ST1866 was the dominant genotype associated with HL-AZM-R isolates., (Copyright © 2018 Wan et al.)

Mycoplasma genitalium is an important pathogen that is transmitted through sexual contact. For patients diagnosed with M. genitalium infection, the current guidelines recommend 1 g of azithromycin as the first-line treatment. Moxifloxacin is used as a second-line drug due to its remarkable efficacy; however, increased use of moxifloxacin to treat M. genitalium infections has caused the emergence of cases of moxifloxacin treatment failure. This meta-analysis aims to estimate the treatment efficacy of moxifloxacin for M. genitalium infection. Electronic databases were searched for articles published from 1983 to the end of May 2016 using the following search terms: ( Mycoplasma genitalium) AND (moxifloxacin OR 1-cyclopropyl-7-(2,8-diazabicyclo(4.3.0)non-8-yl)-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinoline carboxylic acid OR Proflox OR moxifloxacin hydrochloride OR Octegra OR Avelox OR Avalox OR Izilox OR Actira OR [treatment efficacy]). All included studies were published in English; all participants were diagnosed with M. genitalium infection, and microbial cure times were measured within 12 months after treatment. Treatment efficacy was measured as microbial cure at the final follow-up after treatment. In total, 17 studies including 252 participants met the inclusion criteria. The majority of these studies were observational. The random-effects pooled microbial cure rate was 96% (95% confidence interval [CI], 90%-99%; I 2  = 28.59%, P = 0.13). For studies with sample collection deadlines prior to 2010, the pooled microbial cure rate was 100% (95% CI, 99%-100%; I 2  = 0.00%, P = 1.00). For studies with sample collection deadlines of 2010 and later, the pooled microbial cure rate was 89% (95% CI, 82%-94%; I 2  = 0.00%, P = 0.59). The elimination rate of moxifloxacin for M. genitalium infection has decreased from 100% to 89% since 2010. This decline merits considerable attention. We suggest close follow-up to investigate the efficacy of moxifloxacin for treating M. genitalium infections. Additionally, sentinel points should be established to detect mutations in the gyrA/B and parC/E genes, which are associated with moxifloxacin resistance.

Background: Antimicrobial resistance (AMR) and genetic determinants of resistance of N. gonorrhoeae isolates from Hefei, China, were characterized adding a breadth of information to the molecular epidemiology of gonococcal resistance in China., Methods: 126 N. gonorrhoeae isolates from a hospital clinic in Hefei, were collected between January, 2014, and November, 2015. The minimum inhibitory concentration (MIC) of N. gonorrhoeae isolates for seven antimicrobials were determined by the agar dilution method. Isolates were tested for mutations in penA and mtrR genes and 23S rRNA, and also genotyped using N. gonorrhoeae multi-antigen sequence typing (NG-MAST)., Results: All N. gonorrhoeae isolates were resistant to ciprofloxacin; 81.7% (103/126) to tetracycline and 73.8% (93/126) to penicillin. 39.7% (50/126) of isolates were penicillinase producing N. gonorrhoeae (PPNG), 31.7% (40/126) were tetracycline resistant N. gonorrhoeae (TRNG) and 28.6% (36/126) were resistant to azithromycin. While not fully resistant to extended spectrum cephalosporins (ESCs), a total of 14 isolates (11.1%) displayed decreased susceptibility to ceftriaxone (MIC ≥ 0.125 mg/L, n = 10), cefixime (MIC ≥ 0. 25 mg/L, n = 1) or to both ESCs (n = 3). penA mosaic alleles XXXV were found in all isolates that harbored decreased susceptibility to cefixime, except for one. Four mutations were found in mtrR genes and mutations A2143G and C2599T were identified in 23S rRNA. No isolates were resistant to spectinomycin. Gonococcal isolates were distributed into diverse NG-MAST sequence types (STs); 86 separate STs were identified., Conclusions: N. gonorrhoeae isolates from Hefei during 2014-2015, displayed high levels of resistance to antimicrobials that had been recommended previously for treatment of gonorrhea, e.g., penicillin, tetracycline and ciprofloxacin. The prevalence of resistance to azithromycin was also high (28.6%). No isolates were found to be fully resistant to spectinomycin, ceftriaxone or cefixime; however, 11.1% isolates, overall, had decreased susceptibility to ESCs.

Objective: To analyze the gene expression profiling characteristics of peripheral blood mononuclear cells (PBMCs) from patients with secondary syphilis, and gain an insight into the host molecular immune mechanisms involved in Treponema pallidum infection., Methods: Using genome-based high-throughput Illumina sequencing technology, we comprehensively determined the transcriptional difference in PBMCs from 4 secondary syphilis patients and 4 healthy controls, followed by real time PCR to validate the results of Illumina sequencing., Results: Totally, 78 differentially expressed genes were found in the PBMCs of the secondary syphilis patients, among which 16 were associated with the immune system. Significant upregulation was observed in the expressions of pro-inflammatory cytokines and related receptors, such as TNF receptor super-family member 17 (TNFRSF17), IL-17C, IL-21, IL-31 receptor A (IL-31RA), chemokine C-X-C motif ligand 10 (CXCL10), and chemokine (C-C motif) ligand 1 (CCL1), as well as the transcripts for the CD4+ T lymphocytes activation markers CD38, Fc-mediated phagocytosis receptors (FcγR1A, FcγR3B), and complement (C2, SERPING1)., Conclusions: Systemic innate and adaptive immune effecter molecules are involved in the host clearance mechanism of secondary syphilis.

Purpose: To determine the effect of diagnostic ureteroscopy on intravesical recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterec¬tomy (RNU)., Materials and Methods: We conducted a retrospective analysis of 664 patients who were treated with RNU for UTUC from June 2000 to December 2011, excluding those who had concomitant/prior bladder tumors. Of the 664 patients, 81 underwent di¬agnostic ureteroscopy (URS). We analyzed the impact of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan-Meier method. Univariate and multi¬variate analyses were used to determine the independent risk factors., Results: The median follow-up time was 48 months (interquartile range (IQR): 31- 77 months). Patients who underwent ureteroscopy were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality (p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative ureteroscopy have a statistically significant better 2-year (79.3%±0.02 versus 71.4%±0.02, p<0.001) and 5-year intravesical recurrence-free survival rates (64.9%±0.05 versus 44.3%±0.06, p<0.001) than patients who un¬derwent ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006), multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0 stage tumor (p=0.045) were independent predictors of IVR., Conclusions: Diagnostic ureteroscopy is independently associated with intravesical re¬currence after radical nephroureterectomy., Competing Interests: Conflicts of Interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

The complete mitochondrial genome of Reticulitermes labralis (Isoptera: Rhinotermitidae) was determined for its nucleotide sequence of 16 113 bp. Its gene content and organization were identical with other Reticulitermes species. The 13 protein-coding genes (PCGs) have typical ATN initiation codon. But, the stop codons were TAA, TAG and an incomplete termination codon (T) abutting an adjacent tRNA gene. Twenty-two tRNA genes, in addition to tRNASer(AGN) replaced lacking of the DHU stem with a simple loop, showed the typical clover-leaf secondary structure. The A + T-rich region was 1311 bp in length with 65.98% A + T content. In addition to the A + T-rich region, non-coding sequences of the mtDNA genome harbored 17 intergenic spacers. There were three complete repeats of repeat A in CR, which were not discovered in other termite species. Phylogenetic tree based on the 11 complete mitochondrial genome sequences of closely related termite species accords well with morphological phylogenetic analysis.

The separation of reproductive and non-reproductive roles based on caste differentiation is the most prominent characteristic of termites. However, little is known about the mechanism of male reproductive division that underlies caste differentiation. In the present study, testicular development and stage-specific apoptotic patterns were investigated and compared during spermatogenesis in reproductives, workers and soldiers of the termite Reticulitermes labralis. The results showed that male workers were divided into two types, the workers with spermatozoa (WS) and the workers without spermatozoa (WN). Spermatogenesis in WN and soldiers arrested at the spermatocyte stage. Moreover, there were significant differences in testicular size and spermatogenesis among the various castes. The mode of apoptosis in late instar WS was similar to the reproductives, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) analysis. First, the majority of apoptotic cells were spermatogonia, and the spermatogonia of both late instar WS and reproductives exhibited lower apoptotic rates compared with late instar WN and soldiers. Second, the spermatocytes and spermatids showed very little apoptosis in the late instar WS and reproductives, and no TUNEL signal was detected in any of the examined spermatozoa. Our findings suggest that the male workers undergo a basal developmental schema comprising two undifferentiated larval instars, followed by a bifurcated development into either (i) the sexual lineage, in which the workers are able to provide normal spermatozoa to queens, or (ii) the neuter lineage, in which the male workers lose reproductive options. The level of testicular development may explain the significant discrepancies in reproductive capacity among the reproductives, workers and soldiers and reveal the reproductive division in male workers. These differences are controlled by apoptosis during early spermatogenesis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Secondary reproductives develop primarily from nymphs. However, they have been rarely studied; in particular, the development of adultoid reproductives (AR) with floppy wings is still unclear. In this study, the change in juvenile hormone (JH) levels, vitellogenin gene expression, and oogenesis during the development of AR and brachypterous neotenic reproductives (BN) from the last instar nymphs of Reticulitermes labralis are investigated and compared. The results showed that the AR derived from the last instar nymphs by molting, and they were more similar to neotenic reproductives in morphology. In addition, the paired AR were not able to survive in the absence of workers. In R. labralis, the process of the last instar nymphs developing into AR and BN took an increase in JH level as a starting point. The JH level of the last instar nymphs molting into BN was approximately 1.5-fold higher than that of the AR. Additionally, The JHIII level of BN peaked on day 5, and that of AR peaked on day 10, which induced the onset of vitellogenesis in BN and AR, respectively. After molting, the vitellogenin gene expression levels of both BN and AR initially increased and then declined, and the expression levels in the BN were significantly higher than those in the AR. In addition, the oocytes of BN matured earlier than those of the AR, and the number of eggs laid by the BN was higher than the number laid by the AR. Our results demonstrate that, in R. labralis, the last instar nymphs can develop into AR, which are significantly different from BN in their development., (© The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.)

We tested the activity of ETX0914 against 187 Neisseria gonorrhoeae isolates from men with urethritis in Nanjing, China, in 2013. The MIC50, MIC90, and MIC range for ETX0914 were 0.03 μg/ml, 0.06 μg/ml, and ≤0.002 to 0.125 μg/ml, respectively. All isolates were resistant to ciprofloxacin, and 36.9% (69/187) were resistant to azithromycin. Of the isolates, 46.5% were penicillinase-producing N. gonorrhoeae (PPNG), 36% were tetracycline-resistant N. gonorrhoeae (TRNG), and 13% (24 isolates) had an MIC of 0.125 μg/ml for ceftriaxone. ETX0914 may be an effective treatment option for gonorrhea., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Evolving gonococcal antimicrobial resistance (AMR) poses a serious threat to public health. The aim of this study was to: update antimicrobial susceptibility data of Neisseria gonorrhoeae recently isolated in Nanjing, China and identify specific deteminants of antimicrobial resistance and gentoypes of isolates with decreased sensitivity to ceftriaxone., Methods: 334 N. gonorrhoeae isolates were collected consecutively from symptomatic men attending the Nanjing STD Clinic between April 2011 and December 2012. The minimum inhibitory concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone were determined by agar plate dilution for each isolate. Penicillinase-producing N. gonorrhoeae (PPNG) and tetracycline-resistant N. gonorrhoeae (TRNG) were examined and typed for β-lactamase and tetM encoding plasmids respectively. Isolates that displayed elevated MICs to ceftriaxone (MIC ≥0.125 mg/L) were also tested for mutations in penA, mtrR, porB1b, ponA and pilQ genes and characterized by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST)., Results: 98.8% (330/334) of N. gonorrhoeae isolates were resistant to ciprofloxacin; 97.9% (327/334) to tetracycline and 67.7% (226/334) to penicillin. All isolates were susceptible to ceftriaxone (MIC ≤0.25 mg/L) and spectinomycin (MIC ≤32 mg/L). Plasmid mediated resistance was exhibited by 175/334 (52%) of isolates: 120/334 (36%) of isolates were PPNG and 104/334 (31%) were TRNG. 90.0% (108/120) of PPNG isolates carried the Asia type β-lactamase encoding plasmid and 96% (100/104) of TRNG isolates carried the Dutch type tetM containing plasmid. Elevated MICs for ceftriaxone were present in 15 (4.5%) isolates; multiple mutations were found in penA, mtrR, porB1b and ponA genes. The 15 isolates were distributed into diverse NG-MAST sequence types; four different non-mosaic penA alleles were identified, including one new type., Conclusions: N. gonorrhoeae isolates in Nanjing generally retained similar antimicrobial resistance patterns to isolates obtained five years ago. Fluctuations in resistance plasmid profiles imply that genetic exchange among gonococcal strains is ongoing and is frequent. Ceftriaxone and spectinomycin remain treatments of choice of gonorrhea in Nanjing, however, decreased susceptibility to ceftriaxone and rising MICs for spectinomycin of N. gonorrhoeae isolates underscore the importance of maintaining surveillance for AMR (both phenotypic and genotypic).

Aim: To compare the efficacy and safety of photodynamic therapy (PDT) with overlapping multiple spots and single spot for treating circumscribed choroidal hemangioma., Methods: Twenty-two patients (22 eyes) with symptomatic circumscribed choroidal hemangioma received PDT treatment. Fourteen patients received overlapping spots (two to three spots) PDT, whereas eight patients received single-spot PDT. Laser was used at 50J/cm(2) for 83s in the overlapping-spot group and 50J/cm(2) for 166s in the single-spot group. Clinical examination, funduscopy, fluorescein angiography, and ultrasonography were performed at baseline and after treatment., Results: The mean follow-up time was 28.5±8.0 months in the overlapping-spot group and 27.0±5.0 months in the single-spot group. Nine patients (64.2%) had their vision improved over two lines on the Snellen chart, and five patients showed stable visual acuity in the overlapping-spot group. The mean thickness of tumor decreased from 2.7±0.8mm to 1.2±0.9mm, and the mean greatest tumor linear dimension decreased from 7.4±1.5mm to 4.5±3.5mm after treatment. In the single-spot group, two patients (25%) had their vision improved over two lines on the Snellen chart, and six patients had unchanged stable vision. The mean tumor thickness in this group decreased from 2.5±0.7mm to 1.4±1.0mm, and the mean greatest tumor linear dimension decreased from 7.2±1.3mm to 4.7±3.6mm. No significant differences in visual improvement and tumor regression were found between the two groups., Conclusion: Overlapping-spot PDT under appropriate treatment parameters and strategies is as effective and safe as single-spot PDT for treating symptomatic circumscribed choroidal hemangioma. Improved or stabilized visual acuity was achieved as a result of tumor regression.

Background: High tolerance to ethanol is a desirable characteristics for ethanologenic strains used in industrial ethanol fermentation. A deeper understanding of the molecular mechanisms underlying ethanologenic strains tolerance of ethanol stress may guide the design of rational strategies to increase process performance in industrial alcoholic production. Many extensive studies have been performed in Saccharomyces cerevisiae and Escherichia coli. However, the physiological basis and genetic mechanisms involved in ethanol tolerance for Zymomonas mobilis are poorly understood on genomic level. To identify the genes required for tolerance to ethanol, microarray technology was used to investigate the transcriptome profiling of the ethanologenic Z. mobilis in response to ethanol stress., Results: We successfully identified 127 genes which were differentially expressed in response to ethanol. Ethanol up- or down-regulated genes related to cell wall/membrane biogenesis, metabolism, and transcription. These genes were classified as being involved in a wide range of cellular processes including carbohydrate metabolism, cell wall/membrane biogenesis, respiratory chain, terpenoid biosynthesis, DNA replication, DNA recombination, DNA repair, transport, transcriptional regulation, some universal stress response, etc., Conclusion: In this study, genome-wide transcriptional responses to ethanol were investigated for the first time in Z. mobilis using microarray analysis.Our results revealed that ethanol had effects on multiple aspects of cellular metabolism at the transcriptional level and that membrane might play important roles in response to ethanol. Although the molecular mechanism involved in tolerance and adaptation of ethanologenic strains to ethanol is still unclear, this research has provided insights into molecular response to ethanol in Z. mobilis. These data will also be helpful to construct more ethanol resistant strains for cellulosic ethanol production in the future.

Furfural from lignocellulosic hydrolysates is the prevalent inhibitor to microorganisms during cellulosic ethanol production, but the molecular mechanisms of tolerance to this inhibitor in Zymomonas mobilis are still unclear. In this study, genome-wide transcriptional responses to furfural were investigated in Z. mobilis using microarray analysis. We found that 433 genes were differentially expressed in response to furfural. Furfural up- or down-regulated genes related to cell wall/membrane biogenesis, metabolism, and transcription. However, furfural has a subtle negative effect on Entner-Doudoroff pathway mRNAs. Our results revealed that furfural had effects on multiple aspects of cellular metabolism at the transcriptional level and that membrane might play important roles in response to furfural. This research has provided insights into the molecular response to furfural in Z. mobilis, and it will be helpful to construct more furfural-resistant strains for cellulosic ethanol production.

Vascular tone, an important determinant of systemic vascular resistance and thus blood pressure, is affected by vascular smooth muscle (VSM) contraction. Key signaling pathways for VSM contraction converge on phosphorylation of the regulatory light chain (RLC) of smooth muscle myosin. This phosphorylation is mediated by Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK) but Ca(2+)-independent kinases may also contribute, particularly in sustained contractions. Signaling through MLCK has been indirectly implicated in maintenance of basal blood pressure, whereas signaling through RhoA has been implicated in salt-induced hypertension. In this report, we analyzed mice with smooth muscle-specific knockout of MLCK. Mesenteric artery segments isolated from smooth muscle-specific MLCK knockout mice (MLCK(SMKO)) had a significantly reduced contractile response to KCl and vasoconstrictors. The kinase knockout also markedly reduced RLC phosphorylation and developed force. We suggest that MLCK and its phosphorylation of RLC are required for tonic VSM contraction. MLCK(SMKO) mice exhibit significantly lower basal blood pressure and weaker responses to vasopressors. The elevated blood pressure in salt-induced hypertension is reduced below normotensive levels after MLCK attenuation. These results suggest that MLCK is necessary for both physiological and pathological blood pressure. MLCK(SMKO) mice may be a useful model of vascular failure and hypotension.

The available information indicates that estrogen receptor(ER) play a physiological role in the regulation of spermatogenesis in vertebrates. However, the cellular distribution of ER in the testis is poorly understood in invertebrates. The aim of this study was to determine the presence and cellular distribution of ER in the spermatogenesis of termite (Reticulitermes aculabialis). Immunocytochemical analysis showed ER was present in the nucleus of the primary spermatocytes, and the expression of ER was relatively stronger in the primary spermatocytes of the swarming termites. Previous studies have demonstrated the procerebrum of the swarming male termites could strongly secrete FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone) which stimulated estrogen secreting. In conclusion, we demonstrated here for the first time that ER might be an important factor in the regulation of the spermatogenesis of termites, and play an important role for starting and maintaining the meiosis cell division of spermatocytes.

The expression of estrogen receptor(ER) was examined in the oogenesis of termites (Reticulitermes aculabialis) with immunocytochemical localization method. The results showed ER existed in oocytes at the process of differentiation and the process of growth. ER immunopositive substance was localized in the nucleus of oocytes at the differentiation stage and (the cytoplasm of oocytes at the growth stage. On the other hand,previous studies have demonstrated the procerebrum of termites could secrete FSH (Follicle Stimulating Hormone)and LH (Luteinizing Hormone) which stimulated estrogen secreting. These results provide a new morphological proof that "brain-gonad" participates in the regulation of the oogenesis of termites, as have been shown in mammal.

The expression of c-fos protein was examined in the brain of reproduction termite (Reticulitermes aculabialis) with immunocytochemical localization method. The results showed c-fos protein immunoreactivity was found in the procerebrum, deutocerebrum and tritocerebrum of termites at all stages. At last instar nymph and after flying stage, c-fos immunoreactivity of procerebrum was weak, but the female and male termites displayed significantly increased the number of c-fos labeled cells in the protocerebrum at flying stage. On the other hand, previous studies have demonstrated neural cells of procerebrum could strongly secrete FSH (Follicle Stimulating Hormone) and LH (Luteinizing Hormone) which maintained libido and stimulated mating flight. This meaned that c-fos expression of procerebrum involved in hormone regulation in sexual behavior,as have been shown in mammal. In conclusion, we demonstrated here for the first time that c-fos expression of procerebrum of termites involved in sexual behavior. These resulats provided a new morphological proof that neural activation of procerebrum participated in the regulation of sexual behavior of termites.

Objective: To investigate the antimicrobial susceptibility,auxotype, and plasmid profile of Neisseria gonorrhoeae isolates in China and to provide evidence for the development of treatment guideline and policy for control., Methods: Agar dilution was used to detect antimicrobial susceptibility. The auxotype was determined by GC genetic medium. The plasmid was extracted by alkaline cleavage and electrophoresed., Results: A total of 4,976 gonococcal isolates were tested in the last 8 years. The resistant rate for penicillin was 71.60% with PPNG being 15.54%. Tetracycline-resistant (TRNG) isolates accounted for 93.02% with 10.48% high level tetracycline-resistant. The resistant rate for ciprofloxacin was also relatively high (31.78%). The resistant rates for spectinomycin and ceftriaxone were 0.36% and 0.46%. The predominant auxotypes of gonococcal isolates were proto and pro(-) during 1995 - 1996 in Nanjing, accounted for 46.4% and 47.53%, 48.4% and 50.22%, respectively. There were 8 strains harboring 4.2, 5.4, 39.5 kb plasmids and 2 harboring 4.2, 4.9, 5.4, 39.5 kb plasmids in 10 PPNG strains; 2 harboring no plasmid, 28 harboring 4.2, 4.9, 5.4, 39.5 kb plasmids in 30 non-PPNG strains. The 5.4 kb plasmid of PPNG could be digested with restriction endonuclease BamHI while the 5.4 kb plasmid of non-PPNG could not., Conclusion: The gonococcal isolates were highly resistant to penicillin, tetracycline, and ciprofloxacin, while were still sensitive to spectinomycin and ceftriaxone. No significant auxotyping change was found in terms of predominant gonococcal strains in the last two years in Nanjing while 5.4 kb plasmid might be the most prevalent resistant plasmid in Nanjing.