Positive GLI1/INHBA feedback loop drives tumor progression in gastric cancer.

GLI1, a key transcription factor of the Hedgehog (Hh) signaling pathway, plays an important role in the development of cancer. However, the function and mechanisms by which GLI1 regulates gene transcription are not fully understood in gastric cancer (GC). Here, we found that GLI1 induced the proliferation and metastasis of GC cells, accompanied by transcriptional upregulation of INHBA. This increased INHBA expression exerted a promoting activity on Smads signaling and then transcriptionally activated GLI1 expression. Notably, our results demonstrate that disrupting the interaction between GLI1 and INHBA could inhibit GC tumorigenesis in vivo. More intriguingly, we confirmed the N6-methyladenosine (m6A) activation mechanism of the Helicobacter pylori/FTO/YTHDF2/GLI1 pathway in GC cells. In conclusion, our study confirmed that the GLI1/INHBA positive feedback loop influences GC progression and revealed the mechanism by which H. pylori upregulates GLI1 expression through m6A modification. This positive GLI1/INHBA feedback loop suggests a novel noncanonical mechanism of GLI1 activity in GC and provides potential therapeutic targets for GC treatment.

Aging Increases Global Annual Food Greenhouse Gas Emissions up to 300 Million Tonnes by 2100.

The dietary preferences of the elderly population exhibit distinct variations from the overall averages in most countries, gaining increasing significance due to aging demographics worldwide. These dietary preferences play a crucial role in shaping global food systems, which will result in changed environmental impacts in the future such as greenhouse gas (GHG) emissions. We present a quantitative evaluation of the influence of population aging on the changes in GHG emissions from global food systems. To achieve this, we developed regional dietary coefficients (DCs) of the elderly based on the Global Dietary Database (GDD). We then reconciled the GDD with the dataset from the Food and Agriculture Organization of the United Nations (FAO) to calculate the food GHG emissions of the average population in each of the countries. By applying the DCs, we estimated the national food GHG emissions and obtained the variations between the emissions from aged and average populations. We employed a modified version of the regional integrated model of climate and the economy model (RICE) to forecast the emission trends in different countries based on FAO and GDD data. This integrated approach allowed us to evaluate the dynamic relationships among aging demographics, food consumption patterns, and economic developments within regions. Our results indicate that the annual aging-embodied global food GHG emissions will reach 288 million tonnes of CO2 equivalent (Mt CO2e) by 2100. This estimation is crucial for policymakers, entrepreneurs, and researchers as it provides insights into a potential future environmental challenge and emphasizes the importance of sustainable food production and consumption strategies to GHG emission mitigations associated with aging dietary patterns.

Identification of novel covalent JAK3 inhibitors through consensus scoring virtual screening: integration of common feature pharmacophore and covalent docking.

Accumulated research strongly indicates that Janus kinase 3 (JAK3) is intricately involved in the initiation and advancement of a diverse range of human diseases, underscoring JAK3 as a promising target for therapeutic intervention. However, JAK3 shows significant homology with other JAK family isoforms, posing substantial challenges in the development of JAK3 inhibitors. To address these limitations, one strategy is to design selective covalent JAK3 inhibitors. Therefore, this study introduces a virtual screening approach that combines common feature pharmacophore modeling, covalent docking, and consensus scoring to identify novel inhibitors for JAK3. First, common feature pharmacophore models were constructed based on a selection of representative covalent JAK3 inhibitors. The optimal qualitative pharmacophore model proved highly effective in distinguishing active and inactive compounds. Second, 14 crystal structures of the JAK3-covalent inhibitor complex were chosen for the covalent docking studies. Following validation of the screening performance, 5TTU was identified as the most suitable candidate for screening potential JAK3 inhibitors due to its higher predictive accuracy. Finally, a virtual screening protocol based on consensus scoring was conducted, integrating pharmacophore mapping and covalent docking. This approach resulted in the discovery of multiple compounds with notable potential as effective JAK3 inhibitors. We hope that the developed virtual screening strategy will provide valuable guidance in the discovery of novel covalent JAK3 inhibitors.

Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo-YAP1 pathway.

BACKGROUND: Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. METHODS: The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. RESULTS: GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746-179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo-YAP1 pathway in both in vitro and in vivo models. CONCLUSIONS: Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.

PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer.

Ferroptosis is a newly discovered form of regulatory cell death induced by iron-dependent lipid peroxidation. Infection with Helicobacter pylori (H. pylori) is regarded as a high-risk factor for the development of gastric cancer (GC) and is associated with an increase in the levels of reactive oxygen species with activation of oncogenic signaling pathways. However, whether GC arising in the context of infection with H. pylori is correlated with ferroptosis is still unknown. In this study, we demonstrate that H. pylori infection increased the sensitivity of GC cells to RSL3 (RAS-selective lethal3)-induced ferroptosis. The molecular subtypes mediated by ferroptosis-related genes are associated with tumor microenvironment (TME) cell infiltration and patient survival. Importantly, we identified that the expression of phosphorylase kinase G2 (PHKG2) was remarkably correlated with H. pylori infection, metabolic biological processes, patient survival and therapy response. We further found the mechanism of H. pylori-induced cell sensitivity to ferroptosis, which involves PHKG2 regulation of the lipoxygenase enzyme Arachidonate 5-Lipoxygenase (ALOX5). In conclusion, PHKG2 facilitates RSL3-induced ferroptosis in H. pylori-positive GC cells by promoting ALOX5 expression. These findings may contribute to a better understanding of the unique pathogenesis of H. pylori-induced GC and allow for maximum efficacy of genetic, cellular, and immune therapies for controlling ferroptosis in diverse contexts.

Fraxetin alleviates BLM-induced idiopathic pulmonary fibrosis by inhibiting NCOA4-mediated epithelial cell ferroptosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a debilitating lung condition with few available treatments. The early driver of wound repair that contributes to IPF has been extensively identified as repetitive alveolar epithelial damage. According to recent reports, IPF is linked to ferroptosis, a unique type of cell death characterized by a fatal buildup of iron and lipid peroxidation. OBJECTIVE AND METHOD: There is little information on epithelial cells that induce pulmonary fibrosis by going through ferroptosis. In this study, we used bleomycin (BLM) to examine the impact of ferroptosis on IPF in mouse lung epithelial cells (MLE-12). RESULTS: We discovered that BLM increases ferroptosis in MLE-12. Additionally, we found that NCOA4 is overexpressed and plays a key role in the ferroptosis of epithelial cells throughout the IPF process. Using Molecular docking, we found that Fraxetin, a natural component extracted from Fraxinus rhynchophylla, formed a stable binding to NCOA4. In vitro investigations showed that Fraxetin administration greatly decreased ferroptosis and NCOA4 expression, which in turn lowered the release of inflammatory cytokines. CONCLUSION: Fraxetin treatment significantly alleviated BLM-induced lung inflammation and fibrosis. Our findings imply that fraxetin possesses inhibitory roles in ferroptosis and can be a potential drug against IPF.

The impact of the COVID-19 pandemic on global trade-embodied carbon emissions.

We evaluate the response of global supply chains to carbon emissions through compiling multi-regional input-output (MRIO) models for import and export shocks in 14 countries/territories dominated by the COVID-19 crisis. Instead of traditional production-based inventories, we achieve CO2 emissions inventories based on intermediate inputs and final consumption to analyze the connected environmental impacts. In addition, we adopt the available data up to date to construct inventories of carbon emissions involved in imports and exports from different sectors. The results show that global carbon emissions could be decreased by 6.01% during the COVID-19, while export carbon emissions remained basically unchanged. As a result, imported carbon emissions fell by 5.2%, with the energy products sector most affected by the pandemic. Transport sector witnessed 18.42% carbon emission reduction. The impact of developing countries with a large proportion of resource-based industries is comparatively higher than that of developed countries with the technological advantage. International trade plays a crucial role in the choice of supply chain partners to control carbon emissions. Building a sustainable supply chain and reducing the "trade carbon deficit" between countries/regions requires the coordination of all departments of each country/region to promote the trade of energy-saving products, environmental protection services and environmental services.

DEC1 promotes progression of Helicobacter pylori-positive gastric cancer by regulating Akt/NF-κB pathway.

Helicobacter pylori (H. pylori) infection plays a crucial role in the initiation and progression of gastric cancer (GC). Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is dysregulated in some cancers and may regulate cell proliferation in specific contexts. Of note, DEC1 is emerging as one of the important factors regulating cellular responses in microenvironment. However, the triggers and precise regulation mechanism for DEC1 during inflammatory carcinoma transformation of GC are unclear. In this study, we identified DEC1 was upregulated in both H. pylori-infected gastric tissues and GC cells. DEC1 expression was positively associated with H. pylori infection status and GC progression. DEC1-positive expression indicated a poorer prognosis in H. pylori-positive GC. DEC1 was required for H. pylori-induced GC cells proliferation. Mechanistically, H. pylori infection significantly activated Akt/NF-κB signal pathway and this induction depend on DEC1 expression level in GC cells. Importantly, their interaction pathway was further verified by H. pylori-positive gastritis mice model. Taken together, our findings identified a novel function of DEC1 in GC. H. pylori infection induce DEC1 expression, and which leading to the progression of GC through activating Akt/ NF-κB signalling pathway. Blocking DEC1/Akt/NF-κB, therefore, presents a promising novel therapeutic strategy for H. pylori-positive GC.

Exosomes derived from myeloid-derived suppressor cells facilitate castration-resistant prostate cancer progression via S100A9/circMID1/miR-506-3p/MID1.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a major cause of recurrence and mortality among prostate cancer (PCa) patients. Myeloid-derived suppressor cells (MDSCs) regulate castration resistance in PCa. Previously, it was shown that intercellular communication was efficiently mediated by exosomes (Exos), but the role and the mechanism of MDSC-derived Exos in CRPC progression was unclear. METHODS: In this study, the circRNA expression profiles in PC3 cells treated with MDSC-Exo and control cells were investigated using a circRNA microarray. RESULTS: The data showed that circMID1 (hsa_circ_0007718) expression was elevated in PC3 cells treated with MDSC-Exo. Moreover, high circMID1 expression was found in PCa compared with benign prostatic hyperplasia (BPH) tissues and in CRPC patients compared with hormone sensitive prostate cancer (HSPC) patients. Further studies showed that MDSC-Exo accelerated PCa cell proliferation, migration, and invasion, while circMID1 deficiency inhibited MDSC-Exo-regulated CRPC progression in vitro and in vivo. Mechanistically, MDSC-derived exosomal S100A9 increased circMID1 expression to sponge miR-506-3p, leading to increased MID1 expression and accelerated tumor progression. CONCLUSION: Together, our results showed that a S100A9/circMID1/miR-506-3p/MID1 axis existed in MDSC-Exo-regulated CRPC progression, which provided novel insights into MDSC-Exo regulatory mechanisms in CRPC progression.

Application of the IoT in the Food Supply Chain─From the Perspective of Carbon Mitigation.

With the rising demands on supply chain transparency and food security, the rapid outspread of the Internet of Things (IoT) to improve logistical efficiency, and the rising penetration of sensor technology into daily life, the extensive integration of the IoT in the food sector is well anticipated. A perspective on potential life cycle trade-offs in regard to the type of integration is necessary. We conduct life cycle assessment (LCA) integrated with shelf life-food loss (SL-FL) models, showing an overall 5-fold leverage on carbon reduction, which is diet dependent and a function of income. Meat presents the highest leverage, 35 ± 11-times, owing to its high carbon footprint. Two-thirds (65%) of global sensors (1 billion) engaged in monitoring fruits and vegetables can mitigate less than 7% of the total reduced carbon emissions. Despite the expected carbon emission reductions, widespread adoption of the IoT faces multiple challenges such as high costs, difficulties in social acceptance, and regional variability in technological development. Furthermore, changes in the distribution of transportation resources and dealer service models, requirements regarding the accuracy of sensor data analysis, efficient and persistent operation of devices, development of agricultural infrastructure, and farmer education and training have all increased uncertainty. Nonetheless, the research trend in smart sensors toward smaller chips and the potential integration of machine learning or blockchain as further steps make it possible to leverage these advantages to facilitate market penetration. These insights facilitate the future optimization of the application of IoT sensors for sustainability.

Knockdown circZNF131 Inhibits Cell Progression and Glycolysis in Gastric Cancer Through miR-186-5p/PFKFB2 Axis.

Gastric cancer (GC) is a prevalent and heterogeneous malignancy in the digestive system. Increasing studies have suggested that circular RNAs are implicated in GC pathogenesis. This study aimed to explore the biological role and underlying mechanism of circRNA zinc finger protein 131 (circZNF131) in GC. The expression pattern of circZNF131, microRNA-186-5p (miR-186-5p), and 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) mRNA in GC tissues and cells was detected by quantitative real-time polymerase chain reaction. The stability of circZNF131 was verified using ribonuclease R assay. Functional experiments were performed by colony formation assay for cloning ability analysis, transwell assay and wounding healing assay for cell metastasis, and flow cytometry for cell apoptosis. Glycolysis metabolism was investigated by determining the levels of glucose uptake and lactate production. The protein detection of apoptosis- or glycolysis-associated markers, PFKFB2, and Ki-67 was implemented by western blot or immunohistochemistry. Dual-luciferase reporter assay was conducted to identify the interaction between miR-186-5p and circZNF131 or PFKFB2. The role of circZNF131 on tumor growth in nude mice was investigated via xenograft tumor assay. Expression analysis indicated that circZNF131 was upregulated in GC tissues and cells in a stable structure. Functional analyses showed that circZNF131 knockdown suppressed GC cell colony formation ability, migration, invasion and glycolysis metabolism, and induced cell apoptosis. Mechanically, miR-186-5p was a target of circZNF131, and miR-186-5p could bind to PFKFB2. Rescue experiments presented that miR-186-5p inhibition reversed the effects of circZNF131 knockdown on GC cell growth and glycolysis, and PFKFB2 overexpression abolished the impacts of miR-186-5p restoration on GC cell progression. Moreover, circZNF131 could positively modulate PFKFB2 expression via sponging miR-186-5p. In vivo, circZNF131 knockdown hindered GC tumor growth by regulating the miR-186-5p/PFKFB2 axis. circZNF131 could exert an oncogenic role in GC malignant development through the miR-186-5p/PFKFB2 axis, which might provide novel targets for GC treatment.

Targeting phosphatidylinositol 3-kinase gamma (PI3Kγ): Discovery and development of its selective inhibitors.

Phosphatidylinositol 3-kinase gamma (PI3Kγ) has been regarded as a promising drug target for the treatment of advanced solid tumors, leukemia, lymphoma, and inflammatory and autoimmune diseases. However, the high level of structural conservation among the members of the PI3K family and the diverse physiological roles of Class I PI3K isoforms (α, ß, δ, and γ) highlight the importance of isoform selectivity in the development of PI3Kγ inhibitors. In this review, we provide an overview of the structural features of PI3Kγ that influence γ-isoform selectivity and discuss the structure-selectivity-activity relationship of existing clinical PI3Kγ inhibitors. Additionally, we summarize the experimental and computational techniques utilized to identify PI3Kγ inhibitors. The insights gained so far could be used to overcome the main challenges in development and accelerate the discovery of PI3Kγ-selective inhibitors.

A multi-conformational virtual screening approach based on machine learning targeting PI3Kγ.

Nowadays, more and more attention has been attracted to develop selective PI3Kγ inhibitors, but the unique structural features of PI3Kγ protein make it a very big challenge. In the present study, a virtual screening strategy based on machine learning with multiple PI3Kγ protein structures was developed to screen novel PI3Kγ inhibitors. First, six mainstream docking programs were chosen to evaluate their scoring power and screening power; CDOCKER and Glide show satisfactory reliability and accuracy against the PI3Kγ system. Next, virtual screening integrating multiple PI3Kγ protein structures was demonstrated to significantly improve the screening enrichment rate comparing to that with an individual protein structure. Last, a multi-conformational Naïve Bayesian Classification model with the optimal docking programs was constructed, and it performed a true capability in the screening of PI3Kγ inhibitors. Taken together, the current study could provide some guidance for the docking-based virtual screening to discover novel PI3Kγ inhibitors.

Identification of a novel SPT inhibitor WXP-003 by docking-based virtual screening and investigation of its anti-fungi effect.

Serine palmitoyltransferase (SPT) plays the key role on catalysing the formation of 3-ketodihydrosphingosine, which is the first step of the de novo biosynthesis of sphingolipids. SPT is linked to many diseases including fungal infection, making it a potential therapeutic target. Thus, a logical docking-based virtual screening method was used to screen selective SPT inhibitor against fungi, not human. We used myriocin-similarity database to identify compounds with good binding with fungal SPT and poor binding with homology human SPT model. Preliminary bio-assay led to the discovery of a promising inhibitor WXP-003, which displayed good inhibitory activity against diversity fungi strains with MIC ranging from 0.78 to 12.5 µg/mL. WXP-003 could significantly reduce sphingolipids content in fungi and no effect on mouse fibroblast cell line L929. Molecular dynamics simulation depicted that SPT/WXP-003 complex formed the favoured interactions. Taken together, discovery of WXP-003 provided valuable guide for the development of novel anti-fungal agents.

[Clinical application value of liquid dressing after circumcision].

OBJECTIVE: To explore and analyze the effect of liquid dressing in relieving pain and preventing incision adhesion after circumcision and its clinical application value. METHODS: Ninety male patients underwent circumcision in Hangzhou Third People's Hospital from September to November 2019, with the incision covered with liquid dressing + vaseline gauze (group A, n = 30), liquid dressing alone (group B, n = 30) or vaseline gauze only (group C, n = 30). At 2, 4 and 6 days after surgery, we compared the Visual Analogue Scale (VAS) pain intensity at dressing change, incision bleeding after dressing removal and incidence of postoperative complications among the three groups of patients. RESULTS: At 2, 4 and 6 days after surgery, the VAS pain score and incidence of incision bleeding were significantly lower in groups A and B than in C (P < 0.05). At 2 days, both the VAS pain score and incidence of incision bleeding were markedly decreased in group A as compared with those in group B (P < 0.05). At 4 and 6 days, the VAS pain score remained lower in group A than in B (P < 0.05), but the incidence rate of incision bleeding showed no significant difference between the two groups (P > 0.05). No statistically significant differences were observed in the incidence of postoperative complications among the three groups (P > 0.05). CONCLUSIONS: Liquid dressing can reduce pain intensity at dressing change, prevent incision adhesion and consequent dressing change-induced tearing and bleeding, and therefore promote incision healing after circumcision. Its combination with vaseline gauze can achieve an even better effect.

ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection.

Gastric cancer (GC) is a lethal disease, and among its variety of etiological factors, Helicobacter pylori (H. pylori) infection is the strongest risk factor. However, the genetic and molecular mechanisms underlying H. pylori-related GC need further elucidation. We investigated the competing endogenous RNA (ceRNA) network differences between H. pylori (+) and H. pylori (-) GC. The long noncoding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression data from 32 adjacent noncancerous samples and 18 H. pylori (+) and 141 H. pylori (-) stomach adenocarcinoma samples were downloaded from the TCGA database. After construction of lncRNA-miRNA-mRNA ceRNA networks of H. pylori (+) and H. pylori (-) GC, Panther and Kobas databases were used to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, survival analysis was used to discover the key genes. In H. pylori (+) GC, we identified a total of 1,419 lncRNAs, 82 miRNAs, and 2,501 mRNAs with differentially expressed profiles. In H. pylori (-) GC, 2,225 lncRNAs, 130 miRNAs, and 3,146 mRNAs were differentially expressed. Furthermore, three unique pathways (cytokine-cytokine receptor interaction, HIF-1 signaling pathway, and Wnt signaling pathway) were enriched in H. pylori (+) GC. According to the overall survival analysis, three lncRNAs (AP002478.1, LINC00111, and LINC00313) and two mRNAs (MYB and COL1A1) functioned as prognostic biomarkers for patients with H. pylori (+) GC. In conclusion, our study has identified the differences in ceRNA regulatory networks between H. pylori (+) and H. pylori (-) GC and provides a rich candidate reservoir for future studies.

Rational Design of Novel Phosphoinositide 3-Kinase Gamma (PI3Kγ) Selective Inhibitors: A Computational Investigation Integrating 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation.

Phosphoinositide 3-kinase gamma (PI3Kγ) draws an increasing attention due to its link with deadly cancer, chronic inflammation and allergy. But the development of PI3Kγ selective inhibitors is still a challenging endeavor because of the high sequence homology with the other PI3K isoforms. In order to acquire valuable information about the interaction mechanism between potent inhibitors and PI3Kγ, a series of PI3Kγ isoform-selective inhibitors were analyzed by a systematic computational method, combining 3D-QSAR, molecular docking, molecular dynamic (MD) simulations, free energy calculations and decomposition. The general structure-activity relationships were revealed and some key residues relating to selectivity and high activity were highlighted. It provides precious guidance for rational virtual screening, modification and design of selective PI3Kγ inhibitors. Finally, ten novel inhibitors were optimized and P10 showed satisfactory predicted bioactivity, demonstrating the feasibility to develop potent PI3Kγ inhibitors through this computational modeling and optimization.

[5-aminolevulinic acid photodynamic therapy for condyloma acuminata with high-risk HPV infection and local cellular immunoactivity of the patient].

OBJECTIVE: To observe the clinical effects of the 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on condyloma acuminata with high-risk human papillomavirus (HPV) infection and cellular immunoactivity in the local tissue of the patient. METHODS: From January 2015 to January 2017, we treated 47 cases of condyloma acuminata with high-risk HPV infection in our hospital by simple excision of the wart (the control group, n = 21) or 1－5 times of ALA-PDT plus wart excision (the observation group, n = 26) and observed the changes in the number of warts and recurrence at 6 months after surgery. We excised all the warts in the control group and those >5 mm before ALA-PDT and >2 mm at 48 hours after 1－5 times of ALA-PDT in the observation group, followed by examination of the counts of CD4+ and CD8+ T cells, CD4+ / CD8+ ratio, and number of CD68+ macrophages in the local tissue by immunohistochemistry. RESULTS: In the control group, the warts were completely removed in all the 21 cases but recurred in 9 (42.9%) at 6 months after surgery. In the observation group, 5 times of ALA-PDT achieved complete removal of the warts in 16 (61.5%) of the 26 patients, partial removal in 7 (26.9%), and inefficient removal in 3 (11.5%), with a total effective removal rate of 88.5% (23/26), a significantly lower 6-month recurrence rate (11.5% ï¼»3/26ï¼½) than in the control (P < 0.05), but no such severe complications as festering, scarring and pigmentation. Compared with the control group and the baseline, the observation group showed remarkable increases after 1, 3 and 5 times of ALA-PDT in the counts of CD4+ T lymphocytes (31.21 ± 6.23 and 30.27 ± 5.63 vs 56.88 ± 4.72, 54.67 ± 2.84 and 42.62 ± 2.31, P < 0.05) and CD8+ T cells (25.31 ± 3.51 and 27.35 ± 3.78 vs 48.87 ± 2.47, 45.41 ± 3.17 and 37.58 ± 3.32, P < 0.01) and the CD4+ / CD8+ ratio (1.21 ± 0.52 and 1.09 ± 0.37 vs 1.68 ± 0.52, 1.63 ± 0.45 and 1.42 ± 0.13, P < 0.05 or P < 0.01), but exhibited no significant change in the count of CD68+ macrophages in the local tissue (23.31 ± 1.54 and 20.25 ± 1.28 vs 22.31 ± 2.73, 23.17 ± 2.41 and 21.35 ± 3.72, P > 0.05). CONCLUSIONS: ALA-PDT, with its advantages of high efficiency, little invasion and high safety, is effective for the treatment of condyloma acuminata with high-risk HPV infection and it can also improve cellular immunoactivity in the local tissue and reduce recurrence.

[Real-time fluorescence constant-temperature simultaneous amplification and testing of nucleic acid for detection of mycoplasma genitalium infection in the genitourinary tract].

OBJECTIVE: To investigate the infection of reproductive Mycoplasma genitalium (MG) detected by real-time fluorescence constant-temperature simultaneous amplification and testing (SAT) of nucleic acid among patients present at the clinics of urology, gynecology or venereal diseases. METHODS: We retrospectively analyzed the clinical data on 5 711 patients with suspected genitourinary tract (GUT) infection present at the clinics of urology, gynecology or sexually transmitted diseases in Hangzhou Third People's Hospital, Shaoxing People's Hospital and General Hospital of Eastern Theater Command from January 2018 to December 2018. The patients were aged 16－73 (38.77 ± 11.32) years, 3 425 males and 2 286 females. We collected urine samples from 3 666, GUT secretion samples from 2 095, and both urine and GUT samples from 50 of the patients. Using the SAT technique, we detected the infections of MG, Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) in the patients. RESULTS: Of the 5 711 patients, 294 (5.15%) were found MG-positive, with a significantly higher positive rate in the males than in the females (5.96% ï¼»206/3 425ï¼½ vs 3.85% ï¼»88/2 286ï¼½, P < 0.05). The laboratory results with the urine and GUT secretion samples from 50 of the cases showed a consistency rate of 100%. Simple MG infection accounted for 52.04% in the 294 MG-positive cases, 63.11% in the 206 MG-positive males, and 26.13% in the 88 females, with a significantly higher positive rate in the males than in the females (P < 0.05). MG combined with UU infection had the highest rate among the mixed infections in both the males and females and in those aged ≤20 years, even higher in the females than in the males (P < 0.05) and in the ≤20-year-old males than in the ≤20-year-old females (8.65% ï¼»9/104ï¼½ vs 5.13% ï¼»4/78ï¼½, P < 0.05). There were statistically significant differences in the MG-positive rate among different age groups (χ2 = 32.74, P < 0.05). CONCLUSIONS: Among patients with suspected GUT infection, the MG-positive rate is higher in men than in women, with MG + UU-positive as the most common mixed infection, and it decreases with the increase of age. The results of SAT of urine and GUT secretion have a high consistency rate.