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Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on ''click'' chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Abstract MicroRNA (miRNA) and long noncoding RNA (lncRNA) are both regulators of cancer progression. This study sought to discuss the functional mechanism of miR‐96‐5p/lncRNA TRIM52 antisense RNA 1 (head‐to‐head; TRIM52‐AS1) in cervical cancer (CC) cell resistance to cisplatin (DDP). DDP‐resistant CC cell line was established using increasing concentrations of DDP, followed by transfection with miR‐96‐5p inhibitor, or si‐TRIM52‐AS1, or insulin‐like growth factor 2 mRNA binding protein 2 (IGF2BP2) overexpression vector. Expression levels of miR‐96‐5p, TRIM52‐AS1, and IGF2BP2 were determined. Changes in IC50 value to DDP, cell proliferation, and apoptosis rate were evaluated by cell‐counting kit‐8 assay, colony formation, and flow cytometry. The bindings of miR‐96‐5p to IGF2BP2 and TRIM52‐AS1 to IGF2BP2 were verified by dual‐luciferase or RNA pull‐down assays. These experiments revealed an up‐expression of miR‐96‐5p and IGF2BP2 while an under‐expression of TRIM52‐AS1 in CC cells. After DDP treatment, miR‐96‐5p inhibition increased apoptosis and decreased proliferation and DDP resistance. miR‐96‐5p bound to TRIM52‐AS1 and downregulated TRIM52‐AS1 expression, and TRIM52‐AS1 bound to IGF2BP2 to inhibit IGF2BP2 expression. TRIM52‐AS1 inhibition or IGF2BP2 overexpression neutralized the inhibition of silencing miR‐96‐5p on CC cell resistance to DDP. Overall, miR‐96‐5p improved CC cell resistance to DDP by inhibiting TRIM52‐AS1 and promoting IGF2BP2.

Synaptic pruning is important during development and synaptic plasticity. Here, the authors show that the dopamine D2 receptor (Drd2) in the anterior cingulate cortex regulates synaptic pruning, affecting LTD and behaviour in transgenic rats.

Abstract Background To determine the impact of combining clinical simulation scenario training and Information Technology Integrated Instruction (ITII) on the teaching of nursing skills. Methods 120 4th-year students in a nursing program who were enrolled in medical and surgical nursing courses. 61 received innovative instruction (experimental group) and 59 received conventional instruction (control group). The ADDIE model, systematic method of course development that includes analysis, design, development, implementation, and evaluation,was used to build simulation teaching and clinical scenarios and to create and modify objective structure clinical examination (OSCE) scenario checklists for acute myocardial infarction (AMI) care, basic life support and operation of automated external defibrillator (BLS), and subdural hemorrhage (SDH) care. The modified OSCE checklists were assessed for reliability, consistency, and validity. The innovative training included flipped classrooms, clinical simulation scenarios, ITII and blended learning formats. Results The reliability and validity of the OSCE checklists developed in this study were acceptable and comparable or higher than checklists in past studies and could be utilized as an OSCE performance tool. Students in innovative instruction obtained significantly better OSCE performance, lab scores and improvements from the previous year’s grades. Significant differences were found in situational awareness (SA). No strong correlations were found between OSCE scores and clinical internship scores, and no significant differences were found between the groups in overall clinical internship performance. Conclusions Innovative instruction showed better performance than conventional methods in summative evaluation of knowledge components, OSCE formative evaluation and clinical nursing internship scores, as well as improved situational awareness in nursing students.

In nursing education, the diversity of clinical scenarios is complex and dynamic, and it is a challenge for nursing students to learn this clinical knowledge in conventional teaching mechanisms. However, integrating information technology into teaching can promote diversity of learning environment. This study aimed to investigate the effectiveness of teaching mechanisms which combined clinical simulation scenario and Information Technology Integrated Instruction. This study applied innovative experimental teaching in medical–surgical and critical care nursing courses for nursing students in their fourth or fifth year at a five-year junior college. Instructional systems design was combined with clinical simulation scenarios and technology to develop multidimensional teaching strategies. Fifth-year students' overall OSCE mean score was considerably higher than that of fourth-year students; specifically, their scores on basic life support and care for subdural hemorrhage varied substantially. Compared with fourth-year students, fifth-year students performed considerably greater on situational awareness. The results of the present study can be used to develop nursing core competencies and improve the clinical care competency of nursing personnel.

We conducted a systematic literature review to obtain risk population–based fungal disease incidence or prevalence data from China. Data were categorized by risk factors and extrapolated by using most recent demographic figures. A total of 71,316,101 cases (5.0% of the population) were attributed to 12 risk factors and 17 fungal diseases. Excluding recurrent Candida vaginitis (4,057/100,000 women) and onychomycosis (2,600/100,000 persons), aspergillosis (317/100,000 persons) was the most common problem; prevalence exceeded that in most other countries. Cryptococcal meningitis, an opportunistic infection, occurs in immunocompetent persons almost twice as often as AIDS. The pattern of fungal infections also varies geographically; Talaromyces marneffei is distributed mainly in the Pearl River Basin, and the Yangtze River bears the greatest histoplasmosis burden. New host populations, new endemic patterns, and high fungal burdens in China, which caused a huge impact on public health, underscore the urgent need for building diagnostic and therapeutic capacity.

Abstract Cryptococcosis is one of the most common opportunistic infections in both immunocompetent and immunocompromised hosts. Although the cryptococcal antigen (CrAg) lateral flow assay (LFA) has been widely used in clinical settings due to its high sensitivity and specificity, the diagnostic value of a low CrAg LFA titers remains unclear. In this study, we performed a retrospective analysis of 149 HIV-negative patients with low CrAg LFA titers (≤1:10) in a Chinese tertiary hospital from January 2013 to December 2017, to evaluate the diagnostic value of low CrAg LFA titers in serum and cerebrospinal fluid (CSF) at different thresholds. Sensitivity and specificity of low CrAg LFA titers in patients with definitive diagnoses of cryptococcosis were 39.6% (95% CI, 29.7–50.1%) and 100% (95% CI, 69.2–100%), respectively, at a threshold of 1:10 in serum. A sensitivity of 72.9% (95% CI, 62.9–81.5%) and a decreased specificity of 70.0% (95% CI, 34.8–93.3%) were observed at a threshold of 1:5 in serum. No false-positive cases were identified in patients with low CrAg titers in CSF and all positive predictive values (PPVs) were 100%. Among the cases with low serum CrAg titers, lumbar puncture was performed in 97 patients and positive CSF CrAg titers were reported in 6 patients. In conclusion, the results of this study imply that low CrAg LFA titer, either in serum or CSF, is crucial for early diagnosis of cryptococcosis in HIV-negative patients, and lumbar puncture is recommended to be performed routinely for CSF testing when a positive low serum titer is reported. Cryptococcal meningitis should be considered seriously when the CSF CrAg titer is positive.

Tomato chlorosis virus (ToCV), is one of the most devastating cultivated tomato viruses, seriously threatened the growth of crops worldwide. As the vector of ToCV, the whitefly Bemisia tabaci Mediterranean (MED) is mainly responsible for the rapid spread of ToCV. The current understanding of tomato plant responses to this virus and B. tabaci is very limited. To understand the molecular mechanism of the interaction between tomato, ToCV and B. tabaci, we adopted a next-generation sequencing approach to decipher miRNAs and mRNAs that are differentially expressed under the infection of B. tabaci and ToCV in tomato plants. Our data revealed that 6199 mRNAs were significantly regulated, and the differentially expressed genes were most significantly associated with the plant-pathogen interaction, the MAPK signaling pathway, the glyoxylate, and the carbon fixation in photosynthetic organisms and photosynthesis related proteins. Concomitantly, 242 differentially expressed miRNAs were detected, including novel putative miRNAs. Sly-miR159, sly-miR9471b-3p, and sly-miR162 were the most expressed miRNAs in each sample compare to control group. Moreover, we compared the similarities and differences of gene expression in tomato plant caused by infection or co-infection of B. tabaci and ToCV. Taken together, the analysis reported in this article lays a solid foundation for further research on the interaction between tomato, ToCV and B. tabaci, and provide evidence for the identification of potential key genes that influences virus transmission in tomato plants.

AIM: To study the effect of an innovative micro-dissection procedure by radiofrequency ablation (MRA) in removing eyelid nevus. METHODS: Fifty-six consecutive outpatients with eyelid nevus were treated with MRA using a monopolar device. The effect of MRA was determined after following-up for 6mo to 5y. RESULTS: Fifty-two cases (52 eyes, 92.9%) were cured once, and 4 cases (4 eyes, 7.1%) received second treatment for small residual. All cases healed well after surgery, with no pigmentation, no scars, no loss of eyelashes, no deformation of eyelid margin. There was no visual impairment after healing. CONCLUSION: MRA of eyelid nevus using the XL-RFA device is highly efficient without significant complications.

Abstract Background The 2010 Infectious Diseases Society of America (IDSA) guidelines for management of cryptococcal diseases recommend high dose fluconazole (≥ 800 mg/day), either alone or with other antifungal drugs, as alternative anticryptococcal choices. But evidence for its use in the treatment of HIV-uninfected cryptococcal meningitis (CM) remains sparse. Methods A retrospective analysis of HIV-uninfected CM patients who received fluconazole 800 mg/day for salvage therapy from January 2011 to December 2016 at Huashan Hospital, Shanghai, China was performed. Efficacy and safety were assessed, and mortality and prognostic factors evaluated. Results A total of 44 patients were studied including 19 refractory to amphotericin B induction therapy, 8 refractory to fluconazole consolidation therapy (400 mg/d), and 17 intolerant of antifungal drugs. For salvage, 11 patients received triple therapy of high dose fluconazole, amphotericin B and flucytosine, 20 received dual therapy of high dose fluconazole and flucytosine, 13 received monotherapy of high dose fluconazole. Median duration of high dose fluconazole in salvage regimens was 136.5 days (range, 1–667 days). Clinical response rates were 72.1% (31/43) and 83.7% (36/43) when assessed at 2 weeks and the end of salvage therapy, respectively. Adverse events possibly related to high dose fluconazole occurred in 54.5% (24/44) of the patients, and all were mild or moderate. From the initiation of salvage therapy, 1-year all-cause mortality was 13.6% (6 of 44 patients) among the study population with no significant difference in refractory or intolerant patients. Conclusions Adherence to guideline recommendations of high dose fluconazole, alone or in combination with other antifungals, was safe and often effective for salvage therapy of HIV-uninfected CM patients.

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). Keywords: Toll-like receptor, Non-HIV cryptococcal meningitis, Genetic susceptibility, Disease severity, CSF cytokine

Background/Aims: Islet beta cells (β-cells) are unique cells that play a critical role in glucose homeostasis by secreting insulin in response to increased glucose levels. Voltage-gated ion channels in β-cells, such as K+ and Ca2+ channels, contribute to insulin secretion. The response of voltage-gated Na+ channels (VGSCs) in β-cells to the changes in glucose levels remains unknown. This work aims to determine the role of extracellular glucose on the regulation of VGSC. Methods: The effect of glucose on VGSC currents (INa) was investigated in insulin-secreting β-cell line (INS-1) cells of rats using whole-cell patch clamp techniques, and the effects of glucose on insulin content and cell viability were determined using Enzyme-Linked Immunosorbent Assay (ELISA) and Methylthiazolyldiphenyl-tetrazolium Bromide (MTT) assay methods respectively. Results: Our results show that extracellular glucose application can inhibit the peak of INa in a concentration-dependent manner. Glucose concentration of 18 mM reduced the amplitude of INa, suppressed the INa of steady-state activation, shifted the steady-state inactivation curves of INa to negative potentials, and prolonged the time course of INa recovery from inactivation. Glucose also enhanced the activity-dependent attenuation of INa and reduced the fraction of activated channels. Furthermore, 18 mM glucose or low concentration of tetrodotoxin (TTX, a VGSC-specific blocker) partially inhibited the activity of VGSC and also improved insulin synthesis. Conclusion: These results revealed that extracellular glucose application enhances the insulin synthesis in INS-1 cells and the mechanism through the partial inhibition on INa channel is involved. Our results innovatively suggest that VGSC plays a vital role in modulating glucose homeostasis.

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.

Surface fuel loading is a key factor in controlling wildfires and planning sustainable forest management. Spatially explicit maps of surface fuel loading can highlight the risks of a forest fire. Geospatial information is critical in enabling careful use of deliberate fire setting and also helps to minimize the possibility of heat conduction over forest lands. In contrast to lidar sensing and/or optical sensing based methods, an approach of integrating in-situ fuel inventory data, geospatial interpolation techniques, and multiple linear regression methods provides an alternative approach to surface fuel load estimation and mapping over mountainous forests. Using a stratified random sampling based inventory and cokriging analysis, surface fuel loading data of 120 plots distributed over four kinds of fuel types were collected in order to develop a total surface fuel loading model (lntSFL-BioTopo model) and a fine surface fuel model (lnfSFL-BioTopo model) for generating tSFL and fSFL maps. Results showed that the combination of topographic parameters such as slope, aspect, and their cross products and the fuel types such as pine stand, non-pine conifer stand, broadleaf stand, and conifer–broadleaf mixed stand was able to appropriately describe the changes in surface fuel loads over a forest with diverse terrain morphology. Based on a cross-validation method, the estimation of tSFL and fSFL of the study site had an RMSE of 3.476 tons/ha and 3.384 tons/ha, respectively. In contrast to the average loading of all inventory plots, the estimation for tSFL and fSFL had a relative error of 38% (PRMSE). The reciprocal of estimation bias of both SFL-BioTopo models tended to be an exponential growth function of the amount of surface fuel load, indicating that the estimation accuracy of the proposed method is likely to be improved with further study. In the regression modeling, a natural logarithm transformation of the surface fuel loading prevented the outcome of negative estimates and thus improved the estimation. Based on the results, this paper defined a minimum sampling unit (MSU) as the area for collecting surface fuels for interpolation using a cokriging model. Allocating the MSUs at the boundary and center of a plot improved surface fuel load prediction and mapping.

Background/Objective: The aim of this study was to determine whether unilateral manual needling at nonacupoints could result in bilateral strength gain similar to that found in electroacupuncture at specific acupoints. Methods: Fifty healthy male volunteers with an age range of 19–27 years were recruited and randomly allocated into five groups: (1) manual acupuncture and (2) electroacupuncture at two acupoints (ST-36 and ST-39); (3) manual acupuncture and (4) electroacupuncture at two nonacupoints on the tibialis anterior muscle; and (5) control group. The intervention groups received needling in each session on the right leg for 15 minutes in Week 1, 20 minutes in Week 2, and 30 minutes in Weeks 3–8, three sessions per week. The maximal isometric ankle dorsiflexion strength and muscle activation (as determined by twitch interpolation) of both legs were assessed pre, post, 2 weeks post, and 3 weeks post the experimental period. Results: Mixed models (linear) with repeated-measures analysis identified significant strength gains (p

Our previous study revealed that cordycepin features important neuroprotective effects against hypoxic insult by improvement of neuronal electrophysiological function. Modulation on voltage-gated sodium channel (VGSC) in CA1 neurons is the initial event during hypoxia/ischemia. However, no study comprehensively investigated cordycepin on VGSC. Hence, this study investigated modulation effects of cordycepin on VGSC not only in oxygen physiological conditions but also in acute oxygen deprivation injury conditions. Results revealed that cordycepin (80 μM) reduced the amplitude of VGSC currents (INa) (77.6% of control, p

AIM: To investigate the main factors that affecting the positive rate of bacterial culture before the intraocular lens implantation. METHODS:Conjunctival sac specimen form senile patients, who received cataract crystal implantation from December 2010 to December 2012 in our hospital, were collected and cultivated at the following 3 time points: on admission day, after the eye-drops and after the surgical eye preparation. Afterwards, a comparative analysis was made in terms based on of the following factors: age, gender, dominant eye, occupation, days for eye-drops as well as the intervention techniques. RESULTS: Factors such as age, gender, intervention technique were significantly related with the rate of bacterial culture, while factors such as occupation, dominant eye and days for pre-operative eye-drops had few effects on the final results. CONCLUSION: There are both internal factors and external factors affecting the bacterial culture. Inconjunctival sac intervention techniques play a crucial role in the bacterial culture in conjunctival sac, which deserves more attention.

AIM: To learn about the current condition about bacteria contamination of aqueous humor during cataract operation.METHODS: Bacterial culture was conducted of the samples of aqueous humor and conjunctival sac collected from 807 patients during cataract operation from December 2010 to December 2012. Then, the bacterial culture results were analyzed. RESULTS: On average, the bacterial culture positive rate was 0.93%, with no significant difference in the positive rates of samples collected at different times. The average bacterial culture positive rate of conjunctival sac was 9.54%, with significant difference between the positive rates before and after the operation(χ2=37.21, Pstaphylococcus epidermidis(60.00% for aqueous humor and 91.56% for the conjunctival sac). During continuous operations, >6 times of patients' aqueous humor and the positive rate of conjunctival sac bacteria culture is significantly greater than that of ≤5 times of patients. The result of the drug sensitive test indicated that most bacteria in aqueous humor and conjunctival sac were sensitive to Cephalosporins while they were highly resistant to penicillin, erythromycin, tetracycline, and Lomefloxacin. CONCLUSION:Because of the bacterial pollution in the water from most of the conjunctival sac, preoperative conjunctival sac aseptic preparation is essential. Because intraoperative conjunctival sac, even real water may have some bacteria, strengthen the local application of antibiotics can effectively prevent postoperative intraocular infection.