Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

Calcitonin gene-related peptide inhibits neuronal apoptosis in heatstroke rats via PKA/p-CREB pathway.

PURPOSE: The incidence of heatstroke (HS) is not particularly high; however, once it occurs, the consequences are serious. It is reported that calcitonin gene-related peptide (CGRP) is protective against brain injury in HS rats, but detailed molecular mechanisms need to be further investigated. In this study, we further explored whether CGRP inhibited neuronal apoptosis in HS rats via protein kinase A (PKA)/p-cAMP response element-binding protein (p-CREB) pathway. METHODS: We established a HS rat model in a pre-warmed artificial climate chamber with a temperature of (35.5 ± 0.5) °C and a relative humidity of 60% ± 5%. Heatstress was stopped once core body temperature reaches above 41 °C. A total of 25 rats were randomly divided into 5 groups with 5 animals each: control group, HS group, HS+CGRP group, HS+CGRP antagonist (CGRP8-37) group, and HS+CGRP+PKA/p-CREB pathway blocker (H89) group. A bolus injection of CGRP was administered to each rat in HS+CGRP group, CGRP8-37 (antagonist of CGRP) in HS+CGRP8-37 group, and CGRP with H89 in HS+CGRP+H89 group. Electroencephalograms were recorded and the serum concentration of S100B, neuron-specific enolase (NSE), neuron apoptosis, activated caspase-3 and CGRP expression, as well as pathological morphology of brain tissue were detected at 2 h, 6 h, and 24 h after HS in vivo. The expression of PKA, p-CREB, and Bcl-2 in rat neurons were also detected at 2 h after HS in vitro. Exogenous CGRP, CGRP8-37, or H89 were used to determine whether CGRP plays a protective role in brain injury via PKA/p-CREB pathway. The unpaired t-test was used between the 2 samples, and the mean ± SD was used for multiple samples. Double-tailed p < 0.05 was considered statistically significant. RESULTS: Electroencephalogram showed significant alteration of θ (54.50 ± 11.51 vs. 31.30 ± 8.71, F = 6.790, p = 0.005) and α wave (16.60 ± 3.21 vs. 35.40 ± 11.28, F = 4.549, p = 0.020) in HS group compared to the control group 2 h after HS. The results of triphosphate gap terminal labeling (TUNEL) showed that the neuronal apoptosis of HS rats was increased in the cortex (9.67 ± 3.16 vs. 1.80 ± 1.10, F = 11.002, p = 0.001) and hippocampus (15.73 ± 8.92 vs. 2.00 ± 1.00, F = 4.089, p = 0.028), the expression of activated caspase-3 was increased in the cortex (61.76 ± 25.13 vs. 19.57 ± 17.88, F = 5.695, p = 0.009) and hippocampus (58.60 ± 23.30 vs. 17.80 ± 17.62, F = 4.628, p = 0.019); meanwhile the expression of serum NSE (5.77 ± 1.78 vs. 2.35 ± 0.56, F = 5.174, p = 0.013) and S100B (2.86 ± 0.69 vs. 1.35 ± 0.34, F = 10.982, p = 0.001) were increased significantly under HS. Exogenous CGRP decreased the concentrations of NSE and S100B, and activated the expression of caspase-3 (0.41 ± 0.09 vs. 0.23 ± 0.04, F = 32.387, p < 0.001) under HS; while CGRP8-37 increased NSE (3.99 ± 0.47 vs. 2.40 ± 0.50, F = 11.991, p = 0.000) and S100B (2.19 ± 0.43 vs. 1.42 ± 0.30, F = 4.078, p = 0.025), and activated the expression caspase-3 (0.79 ± 0.10 vs. 0.23 ± 0.04, F = 32.387, p < 0.001). For the cell experiment, CGRP increased Bcl-2 (2.01 ± 0.73 vs. 2.15 ± 0.74, F = 8.993, p < 0.001), PKA (0.88 ± 0.08 vs. 0.37 ± 0.14, F = 20.370, p < 0.001), and p-CREB (0.87 ± 0.13 vs. 0.29 ± 0.10, F = 16.759, p < 0.001) levels; while H89, a blocker of the PKA/p-CREB pathway reversed the expression. CONCLUSIONS: CGRP can protect against HS-induced neuron apoptosis via PKA/p-CREB pathway and reduce activation of caspase-3 by regulating Bcl-2. Thus CGRP may be a new target for the treatment of brain injury in HS.

Herbal active small molecule as an immunomodulator for potential application on resistance of common carp against SVCV infection.

Herbal immunomodulators are an important part of prevention and control on viral diseases in aquaculture because of their propensity to improve immunity in fish. The present study was conducted to evaluate the immunomodulatory effect and antiviral activity of a synthesized derivative (serial number: LML1022) against spring viremia of carp virus (SVCV) infection in vitro and in vivo. The antiviral data suggested that LML1022 at 100 µM significantly inhibited the virus replication in epithelioma papulosum cyprini (EPC) cells, and may completely inhibit the infectivity of SVCV virion particles to fish cells by affecting the viral internalization. The results in the related stability of water environments also demonstrated that LML1022 had an inhibitory half-life of 2.3 d at 15 °C, which would facilitate rapid degradation of LML1022 in aquaculture application. For in vivo study, the survival rate of SVCV-infected common carp was increased 30% at least under continuous oral injection of LML1022 at 2.0 mg/kg for 7 d treatment. Additionally, pretreatment of LML1022 on fish prior to SVCV infection also obviously reduced the viral loads in vivo as well as an improved survival rate, showing that LML1022 was potential as an immunomodulator. As an immune response, LML1022 significantly upregulated the immune-related gene expression including IFN-γ2b, IFN-I, ISG15 and Mx1, indicating that its dietary administration may improve the resistance of common carp against SVCV infection.

The Effects of Programmed Cell Death of Mesenchymal Stem Cells on the Development of Liver Fibrosis.

Mesenchymal stem cells have shown noticeable potential for unlimited self-renewal. They can differentiate into specific somatic cells, integrate into target tissues via cell-cell contact, paracrine effects, exosomes, and other processes and then regulate the target cells and tissues. Studies have demonstrated that transplantation of MSCs could decrease the expression and concentration of collagen in the liver, thereby reducing liver fibrosis. A growing body of evidence indicates that apoptotic MSCs could inhibit harmful immune responses and reduce inflammatory responses more effectively than viable MSCs. Accumulating evidence suggests that mitochondrial transfer from MSCs is a novel strategy for the regeneration of various damaged cells via the rescue of their respiratory activities. This study is aimed at reviewing the functions of MSCs and the related roles of the programmed cell death of MSCs, including autophagy, apoptosis, pyroptosis, and ferroptosis, as well as the regulatory pathogenic mechanisms of MSCs in liver fibrosis. Research has demonstrated that the miR-200B-3p gene is differentially expressed gene between LF and normal liver samples, and that the miR-200B-3p gene expression is positively correlated with the degree of liver fibrosis, suggesting that MSCs could inhibit liver fibrosis through pyroptosis. It was confirmed that circulating monocytes could deliver MSC-derived immunomodulatory molecules to different sites by phagocytosis of apoptotic MSCs, thereby achieving systemic immunosuppression. Accordingly, it was suggested that characterization of the programmed cell death-mediated immunomodulatory signaling pathways in MSCs should be a focus of research.

The Feasibility of Applying Artificial Intelligence to Gastrointestinal Endoscopy to Improve the Detection Rate of Early Gastric Cancer Screening.

Convolutional neural networks in the field of artificial intelligence show great potential in image recognition. It assisted endoscopy to improve the detection rate of early gastric cancer. The 5-year survival rate for advanced gastric cancer is less than 30%, while the 5-year survival rate for early gastric cancer is more than 90%. Therefore, earlier screening for gastric cancer can lead to a better prognosis. However, the detection rate of early gastric cancer in China has been extremely low due to many factors, such as the presence of gastric cancer without obvious symptoms, difficulty identifying lesions by the naked eye, and a lack of experience among endoscopists. The introduction of artificial intelligence can help mitigate these shortcomings and greatly improve the accuracy of screening. According to relevant reports, the sensitivity and accuracy of artificial intelligence trained on deep cirrocumulus neural networks are better than those of endoscopists, and evaluations also take less time, which can greatly reduce the burden on endoscopists. In addition, artificial intelligence can also perform real-time detection and feedback on the inspection process of the endoscopist to standardize the operation of the endoscopist. AI has also shown great potential in training novice endoscopists. With the maturity of AI technology, AI has the ability to improve the detection rate of early gastric cancer in China and reduce the death rate of gastric cancer related diseases in China.

Effectiveness and safety of over-the-scope clip in closing perforations after duodenal surgery.

BACKGROUND: Endoscopic resection of duodenal subepithelial lesions (SELs) is a difficult procedure with a high risk of perforation. At present, dealing with perforation after endoscopic resection of duodenal SELs is still considered a great challenge. AIM: To evaluate the effectiveness and safety of an over-the-scope clip (OTSC) in the treatment of perforation post-endoscopic resection of duodenal SELs. METHODS: From May 2015 to November 2019, 18 patients with perforation following endoscopic resection of duodenal SELs were treated with OTSCs. Data comprising the rate of complete resection, closure of intraprocedural perforation, delayed bleeding, delayed perforation, and postoperative infection were extracted. RESULTS: The rate of complete removal of duodenal SELs and successful closure of the perforation was 100%. The median perforation size was 1 cm in diameter. Seventeen patients had minor intraoperative bleeding, while the remaining 1 patient had considerable amount of bleeding during the procedure. Seven patients had postoperative abdominal infections, of which 1 patient developed an abscess in the right iliac fossa and another patient developed septic shock. All 18 patients recovered and were discharged. No delayed bleeding or perforation was reported. The mean time taken to resume normal diet after the procedure was 6.5 d. The mean postoperative hospital stay was 9.5 d. No residual or recurrent lesions were detected during the follow-up period (15-66 mo). CONCLUSION: Closing a perforation after endoscopic resection of duodenal SELs with OTSCs seems to be an effective and reasonably safe therapeutic method.

The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation.

Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.

Use of Artificial Intelligence to Improve the Quality Control of Gastrointestinal Endoscopy.

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists.

Relationship Between Endogenous Hydrogen Sulfide and Pulmonary Vascular Indexes on High-Resolution Computed Tomography in Patients with Chronic Obstructive Pulmonary Disease.

Objective: To explore the relationship between endogenous hydrogen sulfide (H2S) and high-resolution computed tomography (HRCT) indexes in pulmonary vascular remodeling. Methods: A total of 94 stable chronic obstructive pulmonary disease (COPD) patients were recruited for the study．Plasma H2S levels were measured using fluorescence probe. Fluorescence quantitative polymerase chain reaction was used to measure H2S synthase cystathionine-γ-lyase (CSE) mRNA and cystathionine-ß-synthesis enzyme (CBS) mRNA. The main pulmonary artery diameter (mPAD), axial diagonal mPAD, coronal mPAD, sagittal mPAD, right pulmonary artery diameter (RPAD), left pulmonary artery diameter (LPAD), and ascending aortic diameter (AAD) and the percentage of total cross-sectional area of vessels less than 5 mm2 of total lung area (%CSA <5) on HRCT were measured. Pulmonary arterial systolic pressure (PASP) of echocardiography, blood gas analysis, and routine blood tests were performed. Correlation analysis and multivariate linear regression were performed using SPSS 22.0. Results: H2S was negatively correlated with mPAD, axial diagonal mPAD, and sagittal mPAD (r = -0.25~-0.32) and positively correlated with PaO2 (r = 0.35). Relative expression of CSE mRNA was positively correlated with PASP, coronal mPAD, sagittal mPAD, white blood cell count (WBC), and neutrophil count (N) (r = 0.30~0.44). The relative expression of CBS mRNA was positively correlated with PASP, WBC, and N (r = 0.34~0.41). In separate models predicting pulmonary vascular indexes, a 1µmol/L increase in H2S predicted lower pulmonary artery diameter (for axial diagonal mPAD, 0.76mm lower; for mPAD/AAD, 0.68mm lower). All P values were less than 0.05. Conclusion: Endogenous H2S may be involved in pulmonary vascular remodeling, providing a new method for the diagnosis and treatment of COPD. The generation of H2S may be inhibited by hypoxia, inflammation, etc.

Progress of esophageal stricture prevention after endoscopic submucosal dissection by regenerative medicine and tissue engineering.

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective treatment for early esophageal cancer. However, post-ESD esophageal stricture remains a thorny issue. We herein review many strategies for preventing post-ESD esophageal stricture, as well as discuss their strengths and weaknesses. These strategies include pharmacological prophylaxis, esophageal stent and tissue engineering and regenerative medicine treatment. In this review, we summarize these studies and discuss the underlying progress and future directions of tissue engineering and regenerative medicine treatment.

Identification and Validation of a Novel RNA-Binding Protein-Related Gene-Based Prognostic Model for Multiple Myeloma.

BACKGROUND: Multiple myeloma (MM) is a malignant hematopoietic disease that is usually incurable. RNA-binding proteins (RBPs) are involved in the development of many tumors, but their prognostic significance has not been systematically described in MM. Here, we developed a prognostic signature based on eight RBP-related genes to distinguish MM cohorts with different prognoses. METHOD: After screening the differentially expressed RBPs, univariate Cox regression was performed to evaluate the prognostic relevance of each gene using The Cancer Genome Atlas (TCGA)-Multiple Myeloma Research Foundation (MMRF) dataset. Lasso and stepwise Cox regressions were used to establish a risk prediction model through the training set, and they were validated in three Gene Expression Omnibus (GEO) datasets. We developed a signature based on eight RBP-related genes, which could classify MM patients into high- and low-score groups. The predictive ability was evaluated using bioinformatics methods. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and gene set enrichment analyses were performed to identify potentially significant biological processes (BPs) in MM. RESULT: The prognostic signature performed well in the TCGA-MMRF dataset. The signature includes eight hub genes: HNRNPC, RPLP2, SNRPB, EXOSC8, RARS2, MRPS31, ZC3H6, and DROSHA. Kaplan-Meier survival curves showed that the prognosis of the risk status showed significant differences. A nomogram was constructed with age; B2M, LDH, and ALB levels; and risk status as prognostic parameters. Receiver operating characteristic (ROC) curve, C-index, calibration analysis, and decision curve analysis (DCA) showed that the risk module and nomogram performed well in 1, 3, 5, and 7-year overall survival (OS). Functional analysis suggested that the spliceosome pathway may be a major pathway by which RBPs are involved in myeloma development. Moreover, our signature can improve on the R-International Staging System (ISS)/ISS scoring system (especially for stage II), which may have guiding significance for the future. CONCLUSION: We constructed and verified the 8-RBP signature, which can effectively predict the prognosis of myeloma patients, and suggested that RBPs are promising biomarkers for MM.

Novel Targets and Therapeutic Strategies to Protect Against Hepatic Ischemia Reperfusion Injury.

Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects.

Application of laser capture microdissection and polymerase chain reaction in the diagnosis of Trichoderma longibrachiatum infection: a promising diagnostic tool for 'fungal contaminants' infection.

Although Trichoderma species are usually considered to be culture contaminants, an increasing number of case reports have demonstrated their pathogenicity. Current diagnostic tools, including fungal culture, radiology, histopathology, and direct microscopy examination, are often unable to differentiate the pathogenicity of 'fungal contaminants' such as Trichoderma species in patients. Accurate diagnostic tools for 'fungal contaminants' infection have become the urgent needs. To that end, we applicated laser capture microdissection (LCM) and polymerase chain reaction (PCR) to confirm T. longibrachiatum infection for the first time. A 57-year-old man presented with a cough and hemoptysis lasting for more than 40 days. Computed tomography scan revealed a mass at the left hilum. In addition to pulmonary spindle cell carcinoma, fungal hyphae were also detected in histopathological examination. The cultured fungus was identified as T. longibrachiatum using molecular procedures. The results from DNA sequencing of DNA obtained by LCM revealed the identical result. Antifungal susceptibility testing revealed resistance to itraconazole, fluconazole and flucytosine. The patient was managed with oral voriconazole for 4 months. No relapse of Trichoderma infection was observed at a year follow-up visit. Although there are potential disadvantages, LCM-based molecular biology technology is a promising diagnostic tool for 'fungal contaminants' infection.

Development of an Accurate and Proactive Immunomodulatory Strategy to Improve Bone Substitute Material-Mediated Osteogenesis and Angiogenesis.

Background: Treatment of large bone defects represents a major clinical problem worldwide. Suitable bone substitute materials are commonly required to achieve successful bone regeneration, and much effort has been spent to optimize their chemical compositions, 3D architecture and mechanical properties. However, material-immune system interactions are increasingly being recognized as a crucial factor influencing regeneration. Here, we envisioned an accurate and proactive immunomodulation strategy via delivery of IL-4 (key regulator of macrophage polarization) to promote bone substitute material-mediated regeneration. Methods: Four different IL-4 doses (0 ng, 10 ng, 50 ng and 100 ng) were delivered into rat large cranial bone defects at day 3 post-operation of decellularized bone matrix (DBM) material implantation, and the osteogenesis, angiogenesis and macrophage polarization were meticulously evaluated. Results: Micro-CT analysis showed that immunomodulation with 10 ng IL-4 significantly outperformed the other groups in terms of new bone formation (1.23-5.05 fold) and vascularization (1.29-6.08 fold), achieving successful defect bridging and good vascularization at 12 weeks. Histological analysis at 7 and 14 days showed that the 10 ng group generated the most preferable M1/M2 macrophage polarization profile, resulting in a pro-healing microenvironment with more IL-10 and less TNF-α secretion, a reduced apoptosis level in tissues around the materials, and enhanced mesenchymal stem cell migration and osteogenic differentiation. Moreover, in vitro studies revealed that M1 macrophages facilitated mesenchymal stem cell migration, while M2 macrophages significantly increased cell survival, proliferation and osteogenic differentiation, explaining the in vivo findings. Conclusions: Accurate immunomodulation via IL4 delivery significantly enhanced DBM-mediated osteogenesis and angiogenesis via the coordinated involvement of M1 and M2 macrophages, revealing the promise of this accurate and proactive immunomodulatory strategy for developing new bone substitute materials.

Genetic influence of Toll-like receptors on non-HIV cryptococcal meningitis: An observational cohort study.

BACKGROUND: Cryptococcal meningitis (CM) is a significant source of mortality, the pathogenesis of which has not been fully understood, especially in non-HIV infected populations. We aimed to explore the potential genetic influence of Toll-like receptor (TLR) on non-HIV CM. METHODS: This observational cohort study was done in two stages: a discovery stage and a validation stage. A case-control genetic association study was conducted between 159 non-HIV CM patients and 468 healthy controls. TLR SNPs significantly related to susceptibility went further validation in a second cohort of 583 subjects from a certain district. Associations among TLR SNPs, cerebrospinal fluid (CSF) cytokine concentrations, and clinical severity were explored in a third cohort of 99 previously untreated non-HIV CM patients. Logistic regression model was used to determine the independent predictors for disease severity. FINDINGS: In the discovery stage, eight TLR SNPs exhibited significant genetic susceptibility to non-HIV CM, one of which was validated in a population validation of HIV-infected cases while none survived in non-HIV cases. CSF cytokine detections showed that 18 cytokines were significantly over-expressed in severely ill patients. Two of the 8 SNPs (rs5743604 and rs3804099) were also significantly associated with disease severity. Specifically, the rs3804099 C/T genotype was further found to be correlated to 12 of the 18 up-regulated cytokines in severe patients. In addition, high levels of interleukin (IL)-10 in CSF (OR 2·97, 95% CI 1·49-5·90; p = 0·002) was suggested as an independent predictor for severity after adjusted for possible confounders. INTERPRETATION: TLR participates in both the occurrence and the pathogenesis of non-HIV CM. The in situ immune responses of CM were under genetic influence of TLR and contributed to disease severity. FUND: National Natural Science Foundation of China and National Key Basic Research Program of China (973 Program).

Calcimycin Suppresses S100A4 Expression and Inhibits the Stimulatory Effect of Transforming Growth Factor ß1 on Keloid Fibroblasts.

Recent researches have indicated that S100A4 participates in tissue fibrosis, whereas calcimycin inhibits this process as a novel S100A4 transcription inhibitor. However, the relationship and mechanisms between calcimycin and S100A4 in keloid fibroblasts (KFs) remain unknown. The present research was aimed to evaluate the effect of calcimycin on S100A4 expression and pathogenesis in KFs. Keloid fibroblasts were cultured and exposed to different concentrations of calcimycin in the absence or presence of transforming growth factor ß1 (TGF-ß1). The results showed that the expression of S100A4 was significantly increased in keloid derived fibroblasts compared with normal skin fibroblasts. Calcimycin depressed S100A4 in a concentration- and time-dependent manner. Moreover, calcimycin suppressed TGF-ß1-induced collagen type I, fibronectin, and α-smooth muscle actin expression and cell viability in cultured KFs. Furthermore, calcimycin modulated expression of TGF-ß/Smad target genes Smad7 and phosphorylation of TGF-ß1-induced Smad2/3. This research for the first time confirmed the presence of S100A4 in KFs. Calcimycin inhibits the expression of S100A4, as well as KF proliferation and migration and extracellular matrix (ECM) synthesis. Taken together, these results indicate that calcimycin might be a therapeutic candidate to keloid or other related fibrotic disorders.

Role of Homeodomain-Interacting Protein Kinase 2 in the Pathogenesis of Tissue Fibrosis in Keloid-Derived Keratinocytes.

Epithelial-mesenchymal transition (EMT) plays a critical role in fibrotic keloid formation, which is characterized by excessive collagen and extracellular matrix synthesis and deposition. Growing evidence suggests that the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) acts upstream of several major fibrosis signaling pathways; however, the role of HIPK2 in the keloid fibrogenesis remains unknown. In the current study, we investigated the roles of HIPK2 in the pathogenesis of keloids. Primary normal skin and keloid keratinocytes were cultured and pretreated with transforming growth factor (TGF)-ß1. Next, keratinocytes were transfected with scrambled small interfering RNA (siRNA) and anti-HIPK2 siRNA. The TGF-ß1-associated HIPK2 alterations were investigated by quantitative real-time polymerase chain reaction. Protein levels were analyzed by western blotting. The HIPK2 was markedly increased in the keloid-derived keratinocytes compared with normal skin keratinocytes. In addition, HIPK2 induced the expression of EMT markers in normal skin keratinocytes by TGF-ß1-SMAD family member 3 (SMAD3). The effect of TGF-ß1-related EMT markers and SMAD3 phosphorylation in response to added TGF-ß1 was significantly abrogated when the cells were transfected with HIPK2 siRNA. We conclude that HIPK2 is a crucial factor in the pathogenesis of keloids, suggesting that HIPK2 might be a novel potential drug target for antikeloid therapy.

Prevalence characteristics of cervical human papillomavirus (HPV) genotypes in the Taizhou area, China: a cross-sectional study of 37 967 women from the general population.

OBJECTIVES: High-risk human papillomaviruses (hrHPVs) are highly prevalent worldwide, and HPV genotypes differ between geographical regions; however, sexually transmitted HPV may lead to cervical carcinogenesis. The objective of this cross-sectional study was to estimate the prevalence characteristics of cervical HPV genotypes in Taizhou, Southeast China. SETTING AND PARTICIPANTS: A population-based sample of 37 967 eligible women (median age: 41.6; range: 15-90 years) visiting the Taizhou ENZE Medical Center in Taizhou (2012-2016) was analysed. HPV genotyping was performed on the collected specimens using a GP5+/bioGP6+-PCR/MPG assay by Luminex 200, which simultaneously identifies 27 different HPV genotypes and the ß-globin gene (internal control). RESULTS: The overall HPV infection rate was 22.8% in the Taizhou-based population, and the prevalence of high-risk HPV, low-risk HPV and mixed high-risk and low-risk HPV infection was 14.2%, 5.7% and 3.0%, respectively. The most prevalent genotypes were HPV52 (19.7%), 16 (11.9%), 58 (11.5%), 39 (7.2%), 18 (6.6%) and 56 (5.6%). The rate of multiple-type HPV infection was 5.7% in the whole population, and the HPV52+58, HPV16+52 and HPV16+18 mixed genotypes were most common in women with multiple infections. The age-specific HPV prevalence showed a bimodal curve, with a first peak below the age of 21 years (41.6%), followed by a second peak in the age group of 56-60 years (28.5%). Moreover, the HPV infection rate differed significantly between the outpatient and physical examination groups (24.0% vs 19.5%, p<0.0001). Further data comparisons showed that the distribution of HPV genotypes varied markedly between the two groups. CONCLUSIONS: Data from this study could be valuable for HPV-based cervical cancer screening efforts in certain areas, support the local vaccination programme in the Taizhou region and facilitate future diagnosis and treatment of HPV diseases.

A case of abdominal enteric cyst in China.

To investigate a case of abdominal enteric cyst in China. The patient was admitted to the china-Japan Friendship Hospital of Jilin University, which was due to intermittent pain in the left side for the last 4 months. In this surgery, CT was used to diagnose the basic condition of the patient. Surgery was used for Treatment of patients with diseases. As soon as patients have been successfully operated by laparoscopic surgery.

A case of IV degree on acute radiation dermatitis in China.

This report investigates the nursing procedure of a case of adjuvant therapy of rectal cancer on IV degree of acute radiation dermatitis patients in the penis and scrotum junction. The lesion degree gradually increased. Fixation of the dressing was difficult in the penis and scrotum junction. The concept of wet healing with new dressings was used in patient. The silver ion dressings were used in inhibiting infection, and the wound was covered by the rimmed foam dressings. When it comes to the shaping period, water gel transparent paste was applied instead to cover the wound. The patient was just into the surgical treatment in the wound healed after six days.