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In this study, a new type of highly porous ceramic was successfully fabricated from α-Al2O3 whiskers and nano-sized Al2O3 particle slurry by vacuum infiltration with the subsequent annealing in air. It was found that with an increase in the alumina slurry amount or sintering temperature, the porosity of the foam ceramic decreased while its compressive strength increased. The optimal alumina slurry content and sintering temperature were equal to 4 g, and 1350 °C, respectively. The as-synthesised porous foam ceramic exhibited a low density of 0.65 g/cm3, high porosity of 83.51%, high compressive strength of 3.84 MPa, and low thermal conductivity of 1.37 W/m⋅K at room temperature, suggesting its potential applications in high-temperature gas filtration and thermal insulation materials.

PURPOSE Oesophageal squamous cell carcinoma (ESCC) patients have severe symptom burden after oesophagectomy; however, longitudinal studies of symptom recovery after surgery are scarce. This study used longitudinal patient-reported outcome (PRO)-based symptoms to identify severe symptoms and profile symptom recovery from surgery in patients undergoing oesophagectomy. METHODS Oesophageal cancer patients (N = 327) underwent oesophagectomy were consecutively included between April 2019 and March 2020. Data were extracted from the Sichuan Cancer Hospital's Esophageal Cancer Case Management Registration Database. Symptom assessment time points were pre-surgery and 1, 3, 5, 7, 14, 21, 30, and 90 days post-surgery using the Chinese version of the MD Anderson Symptom Inventory. And each symptom was rated on an 11-point scale, with 0 being 'not present' and 10 being 'as bad as you can imagine'. The symptom recovery trajectories were profiled using mixed effect models and Kaplan-Meier analysis. RESULTS The most-severe symptoms on day 1 after oesophagectomy were pain, fatigue, dry mouth, disturbed sleep, and distress. The severity of symptoms peaked on day 1 after surgery. The top two symptoms were fatigue (mean: 5.44 [SD 1.88]) and pain (mean: 5.23 [SD 1.29]). Fatigue was more severe 90 days after surgery than at baseline (mean: 1.77 [SD 1.47] vs 0.65 [SD 1.05]; P

Primary biliary cholangitis (PBC) is a chronic progressive cholestatic liver disease. In recent years, researchers have found that cysteine-rich angiogenic inducer 61 (Cyr61, also known as CCN1) has a potential role in reducing portal inflammation in patients with PBC. This study aimed to explore the relationship between Cyr61 and PBC to provide new ideas and an experimental basis for the clinical treatment of PBC. After induction of the overexpression of Cyr61 in a mouse model of PBC using recombinant adenovirus, hematoxylin and eosin staining and pathological scores were used to indicate intrahepatic inflammation and bile duct damage. Real-time PCR was used to detect changes in inflammation-related cytokines in the liver. To further study the mechanism, we assessed whether Cyr61 protects bile duct epithelial cells from cytotoxic effects. Serum and hepatic Cyr61 levels were increased in the murine model of PBC. Overexpression of Cyr61 alleviated hepatic inflammation and bile duct injury in vivo. Cyr61 inhibited the cytotoxic effects of CD8+ T cells by acting on biliary epithelial cells (BECs) in vitro. Our results provide novel insight into the pathogenesis of PBC and suggest that Cyr61 plays a dominant role in the cytotoxic effects on BECs in PBC. Consequently, therapeutic strategies targeting Cyr61 could be a potent therapy for PBC.

Background and aims An increasing attention to the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents has been gained recently. However, the results are inconsistent. Therefore, we conducted a meta-analysis to examine the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents. Methods and results Eligible randomized controlled trials (RCTs) were identified by searching PubMed, EMBASE and Web of Science. The results of this study are synthetized and reported in accordance with the PRISMA statement. GRADE system was used to assess the certainty of evidence. A total of 9 RCTs were identified and included in the meta-analysis. We found that vitamin D supplementation did not affect the changes of cardiometabolic risk markers including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), body mass index (BMI), waist circumferences, systolic blood pressure (SDP) and diastolic blood pressure (DBP). However, vitamin D supplementation showed a beneficial effect on fasting glucose (MD, −1.54 mg/dl, 95% CI -2.98 to −0.10) and TG (MD, −24.76 mg/dl, 95% CI -37.66 to −11.86) in the sub-group analysis of total vitamin D supplementation ≥ 200,000 IU. Conclusions Vitamin D supplementation appeared to have a beneficial effect on reducing fasting glucose and TG level when total vitamin D supplementation ≥200,000 IU but not HDL-C, LDL-C TC, blood pressure and waist circumferences levels in children and adolescents. Further studies are needed to address this issue.

The development of IoT techniques and the automation enabled by trigger-action platforms have brought great convenience to human life. However, with time the proliferating IoT devices will eventually overwhelm such platforms. Specifically, the ever-increasing huge amount of linkage rules significantly challenge the response rate as well as the efficiency of conflict rule detection, which will lead to terrible user experience and disastrous security issues. In this work, we develop a rule engine system for large-scale trigger-action applications. The key insight is that the linkage rules can be executed independent from the central cloud platform, which only require edge-side gateways and an efficient addressing strategy. The platform-side maintains an global image consisting of mappings between rules and gateway addresses, while edge-side rule engine is designed based on an open source tool, i.e., Drools. The implemented RETE algorithm helps to carry out large-scale linkage rules. In addition, we design a lightweight yet effective conflict detection algorithm that categorizes those rules into several types to downgrade the computation complexity. Experiments prove that the system can reduce the resource consumption of the platform-side and remarkably enhance the response speed. Moreover, our system also achieve a high efficacy when detecting conflicts.

Background High-frequency rTMS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated mixed effects on chronic and provoked pain. Objectives/Methods In this study, a meta-analysis was conducted to characterise the potential analgesic effects of high-frequency rTMS over the DLPFC on both chronic and provoked pain. Results A total of 626 studies were identified in a systematic search. Twenty-six eligible studies were included for the quantitative review, among which 17 modulated chronic pain and the remaining investigated the influence on provoked pain. The left side DLPFC was uniformly targeted in the chronic pain studies. While our data identified no overall effect of TMS across chronic pain conditions, there was a significant short-term analgesia in neuropathic pain conditions only (SMD = −0.87). In terms of long-lasting analgesia, there was an overall pain reduction in the midterm (SMD = −0.53, 24.6 days average) and long term (SMD = −0.63, 3 months average) post DLPFC stimulation, although these effects were not observed within specific chronic pain conditions. Surprisingly, the number of sessions was demonstrated to have no impact on rTMS analgesia. In the analysis of provoked pain, our data also indicated a significant analgesic effect following HF-rTMS over the DLPFC (SMD = −0.73). Importantly, we identified a publication bias in the studies of provoked pain but not for chronic pain conditions. Conclusions Overall, our findings support that HF-DLPFC stimulation is able to induce an analgesic effect in chronic pain and in response to provoked pain. These results highlight the potential of DLPFC-rTMS in the management of certain chronic pain conditions and future directions are discussed to enhance the potential long-term analgesic effects.

Non-melanoma skin cancer (NMSC) is the most common malignancy. Photodynamic therapy (PDT) is effective for the treatment of certain NMSCs. However, the clinical response rates of some NMSCs to single PDT are still far from ideal. The reason may be that PDT has shown limited efficacy in managing thicker NMSCs. To explore the efficacy and safety of dermabrasion combined with PDT (D-PDT) for the treatment of NMSCs. This was a retrospective, single-arm, multi-centre study. In total, 172 tumours from 40 patients were treated with D-PDT during the study period. The mean follow-up period was 40 months (range 15–110 months). D-PDT was performed with 633-nm red light at 80 m W/cm2 after lesion dermabrasion and 4 h of photosensitizer exposure. Six nodular basal cell carcinomas (nBCCs) from 6 patients, 9 squamous cell carcinomas (SCCs) from 9 patients, 17 Bowen diseases (BDs) from 10 patients and 140 actinic keratoses (AKs) from 15 patients treated with D-PDT were examined in this study. Only two patients with three AKs experienced recurrence over 12 months. The mean final follow-up periods of patients with AKs, BDs, nBCCs and SCCs were 30, 33, 45 and 60 months, respectively. Thirty-four of the 40 patients treated with D-PDT reported excellent or good cosmetic results. The mean Dermatology Life Quality Index (DLQI) scores of the patients improved significantly after treatment (estimated MD 9.72 [95% CI 8.69 to 10.75]; p

As competition between the United States and Russia intensifies, the importance of nuclear weapons is rising and innovation with regard to associated technologies is gaining momentum in both countries. The other regional nuclear-armed states, such as India, Pakistan, and the Democratic People’s Republic of Korea (North Korea), also have impetus to implement their own nuclear modernization plans. The Asia–Pacific region seems to be on the brink of a strategic arms race amidst bleak international arms control and related progress. As a permanent member of the UN Security Council and a nuclear-weapon state, China has played constructive roles in the international arms control process and should take on more responsibilities in this tough era.

In recent years, severe air pollution has had a serious impact on the health and economy of residents and has attracted great attention. Due to the spatial separation between consumption and production, the transfer of PM2.5 pollution and its health and economic effects caused by interprovincial trade have not been taken seriously. In this study, economic, atmospheric, and epidemiological models were combined to assess air pollution transfer and its health and economic impacts that are attributed to provincial trade in China. The analyses were performed under the PM2.5 transfer scenario in which economically developed areas in eastern China transferred many health and economic impacts to inland areas through interprovincial trade in 2012. As a result of interprovincial trade, 1980 (95% CI 0, 4114) extra deaths and 208,000 (95% CI 74.5, 395.6) additional illnesses accrued, but 0.184 (95% CI 0.017, 0.372) billion USD of residents' economic loss was avoided in China. The results illustrate the serious impact of domestic trade on regional health and economics. It is necessary to comprehensively consider supply chains in designing policies to mitigate the negative health and economic impacts of air pollution across China.

Thalassemia is a common monogenic disease in southwestern China, especially in Guizhou province. In this study, 18 309 neonates were examined for thalassemia. The thalassemia carrier rate was 12.90%, which is associated with geographical regions, with carrier frequencies significantly differing between regions (p < 0.0001). The carrier rates for α-thalassemia and β-thalassemia were 8.91% and 3.36%, respectively. There are 22 genotypes identified among 1632 α-thalassemia cases, and 18 genotypes detected among 615 β-thalassemia cases. The birthrates of individuals with intermediate thalassemia and β-thalassemia major were 0.153% and 0.055%, respectively. Methodologically, NGS-Gap-PCR is superior to traditional detection methods, with 65 more cases detected by NGS-Gap-PCR. Since thalassemia-rich genotypes were highly prevalent in this region, early detection of thalassemia carriers would be meaningful for genetic counseling and prevention/treatment of thalassemia. NGS-Gap-PCR provides a powerful tool for neonate genetic testing and clinical diagnosis of thalassemia, especially in high-prevalence regions.

OBJECTIVES To compare the clinical outcomes of anterior controllable antedisplacement fusion (ACAF), a new surgical technique, with laminoplasty for the treatment of multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) based on a 2-year follow-up. METHODS Clinical data of 53 patients (21 by ACAF and 32 by laminoplasty) who have accepted surgery for treatment of cervical myelopathy caused by multilevel severe OPLL (occupying rate ≥ 50%) from March 2015 to March 2017 were retrospectively reviewed and compared between ACAF group and laminoplasty group. Operative time, blood loss, and complications of the two groups were recorded. Radiographic parameters were evaluated pre- and postoperatively: cervical lordosis on X-ray, space available for the cord (SAC) and the occupying ratio (OR) on computed tomography (CT), and the anteroposterior (AP) diameter of the spinal cord at the narrowest level and the spinal cord curvature on magnetic resonance imaging (MRI). Japanese Orthopaedic Association (JOA) scoring was used to evaluate neurologic recovery. Statistical analysis was conducted to analyze the differences between two groups. The Mann-Whitney U test and chi square test were used to compare categorical variables. unpaired t test was used to compare continuous data. RESULTS All patients were followed up for at least 24 months. The operative time was longer in ACAF group (286.5 vs 178.2 min, P 0.05). Less complications were observed in ACAF group than in laminoplasty group (one case [4.7%] of C5 palsy and one case [4.7%] of cerebrospinal fluid [CSF] leakage in ACAF group; four cases [12.5%] of C5 palsy, two cases [6.3%] of CSF leakage, and four cases [12.5%] of axial symptoms in laminoplasty group). The mean JOA score at last follow-up (14.6 vs 12.8, P

Background: Sublingual immunotherapy (SLIT) had good effectiveness for children with allergic rhinitis (AR). However, no studies explored the effect of persistent allergen exposure on SLIT treatment. Coronavirus disease 2019 (COVID-19) restricts outdoor activities of children significantly. We aimed to evaluate the effectiveness of SLIT during this special period. Methods: A total of 335 AR children who sensitize to house dust mite (HDM) undergoing SLIT were recruited in this study. The clinical effectiveness and safety were evaluated at different time points using symptom and medication scores. The serum total IgE and specific IgE (sIgE) at different time points were detected by using the Unicap system. Results: The total nasal symptoms score (TNSS) and total medication score (TMS) during the epidemic of COVID-19 increased significantly compared with the same period last year (p < 0.05), despite that they were still significantly lower than baseline levels (p < 0.05). The occurrence of adverse reactions at different time points had no significant differences. We also found that the family of the good response group had more frequent bedding cleaning. Both the tIgE and sIgE levels had no significant changes during SLIT treatment. Conclusion: Our results suggest that continuous HDM exposure reduced the effectiveness of SLIT, whereas effective reduction of HDM levels by frequent bed cleaning will be helpful during the SLIT treatment.

In recent years, impressive progress has been made in developing high‐performance perovskite light‐emitting diodes (PeLEDs) with efficiencies comparable to those of traditional organic light‐emitting diodes (OLEDs). It is convinced that the position of exciton recombination zone is crucial for the performance of the LEDs, however, the dynamics of the exciton recombination zone in PeLEDs and its influence on the performance of PeLEDs remain unclear. Herein, luminescent quantum‐dots (QDs) sensing layers with different energy band landscape and electric properties are introduced into PeLEDs as probers to investigate the position of recombination zone. Consequently, it is found that the band offset between the perovskite layer and the adjacent layer is vital to the position of recombination zone. Modulating the recombination zone towards the bulk of the emission layer helps to improve the device performance as well as the operational stability.

The design and operation of hybrid energy systems, which are relevant to remote islands characterized by energy and water supply shortage, have been extensively investigated. However, determining t...

Background. Interleukin-17 plays important roles in allergic diseases. Several studies proved that leptin promoted Th17 immune responses by inducing RORγt transcription. ILC2 is an important member of the early stage of immune response. Therefore, we aimed to explore the effect of leptin on the IL-17 production by ILC2 in AR in this study.Methods. Fifteen AR patients and fifteen healthy controls were enrolled. Serum leptin levels were measured, and their correlation with the frequency of IL-17+ ILC2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. ILC2 was stimulated by leptin, and the expression of IL-17, IL-5, and IL-13 was detected by ELISA. The correlated pathways were confirmed by real-time PCR.Results. We found that serum leptin and the frequency of IL-17-producing ILC2s in AR were significantly higher compared with those in controls. After being incubated with leptin, the frequency of IL-17+ ILC2 cells and IL-17 production from ILC2 was upregulated compared with that in controls. We also found that leptin induced RORγt and Ahr expression by ILC2. Moreover, leptin-induced IL-17-producing ILC2 concomitantly expressed IL-5 and IL-13.Conclusions. Our data provide preliminary evidence that leptin-induced IL-17 production from ILC2 cells is dependent on RORγt and Ahr expression and the blockade of leptin may be a promising target for the treatment of AR.

Energy consumption monitoring technology plays a very important role in the realization of intelligent building energy saving, but it is not accepted widely in China. The main reasons for this are the low public energy-saving awareness and incomplete informational policy instruments; thus, studying how informational policy instruments affect the adoption of energy consumption monitoring technology and the impact of energy-saving awareness is of great significance to the widespread acceptance of energy consumption monitoring technology and its role in the realization of intelligent building energy saving. This paper introduces informational policy instruments and energy-saving awareness into technology acceptance model and builds an extended technology acceptance model. A questionnaire survey of 298 respondents who related to the operation and management of public buildings was used to explore the effect mechanism of informational policy instruments on adopting energy consumption monitoring technology. The results show that (1) informational policy instruments have no direct impact on the acceptance of energy consumption monitoring technology (2) and energy-saving awareness, attitudes, perceived usefulness, and perceived ease of use can mediate the relationship between informational policy instruments and behavioral intention of adopting energy consumption monitoring technology, namely, informational policy instruments can affect behavioral intention through six paths which are informational policy instruments ➔ energy-saving awareness ➔ behavioral intention, informational policy instruments ➔ energy-saving awareness ➔ attitudes ➔ behavioral intention, informational policy instruments ➔ attitudes ➔ behavioral intention, informational policy instruments ➔ perceived ease of use ➔ behavioral intention, informational policy instruments ➔ perceived ease of use ➔ perceived usefulness ➔ behavioral intention, informational policy instruments ➔ perceived usefulness ➔ behavioral intention. Finally, relevant policies and suggestions are put forward based on the results.

To compare the cosmetic efficacy of the transplantation of follicles with intact and non-intact hair bulbs in the treatment for vitiligo.The single-hair follicle units with intact hair bulbs and un-intact hair bulbs were transplanted into the skin of vitiligo. The diameters of regrowing hair shafts and repigmentation of implanted follicles were detected analyzed by dermatoscopy (Beining BN-PFMF Skin and Hair Visualizer).The survival rates of follicles with intact and non-intact hair bulbs were 60.00% and 50.62%, respectively. The average diameters of hair shafts and repigmentation of the two groups were 92.83 ± 7.26 µm vs 55.86 ± 2.64 µm (Single follicle transplantation was an alternative effective choice for the treatment of vitiligo. The skin implanted with follicle with non-intact hair bulb was less hairy.

BACKGROUND Liver failure has high mortality and poor prognosis, and establishing new reliable markers for predicting its prognosis is necessary. Mucosal-associated invariant T (MAIT) cells are a novel population of innate-like lymphocytes involved in inflammatory liver disease, and their potential role in liver failure remains unclear. AIM To investigate alteration of circulating MAIT cells and assess its prognostic value in patients with hepatitis B virus (HBV)-related liver failure. METHODS We recruited 55 patients with HBV-related liver failure, 48 patients with chronic hepatitis B and 40 healthy controls (HCs) from Nantong Third People's Hospital Affiliated to Nantong University. Peripheral blood mononuclear cells were isolated, and the percentage and number of circulating MAIT cells were detected by flow cytometry. Plasma levels of interleukin (IL)-7, IL-12p70, IL-18 and interferon-α were measured by Luminex assay. RESULTS Circulating MAIT cells were significantly decreased in HBV-related liver failure patients (percentage: 2.00 ± 1.22 vs 5.19 ± 1.27%, P < 0.0001; number: 5.47 ± 4.93 vs 84.43 ± 19.59, P < 0.0001) compared with HCs. More importantly, there was a significant reduction of MAIT cells in patients with middle/late-stage compared with early-stage liver failure. Circulating MAIT cells partially recovered after disease improvement, both in percentage (4.01 ± 1.21 vs 2.04 ± 0.95%, P < 0.0001) and in cell count (17.24 ± 8.56 vs 7.41 ± 4.99, P < 0.0001). The proportion (2.29 ± 1.01 vs 1.58 ± 1.38%, P < 0.05) and number (7.30 ± 5.70 vs 2.94 ± 1.47, P < 0.001) of circulating MAIT cells were significantly higher in the survival group than in the dead/liver transplantation group, and the Kaplan-Meier curve showed that lower expression of circulating MAIT cells (both percentage and cell count) predicted poor overall survival (P < 0.01). Also, the levels of IL-12 (20.26 ± 5.42 pg/mL vs 17.76 ± 2.79 pg/mL, P = 0.01) and IL-18 (1470.05 ± 1525.38 pg/mL vs 362.99 ± 109.64 pg/mL, P < 0.0001) were dramatically increased in HBV-related liver failure patients compared with HCs. CONCLUSION Circulating MAIT cells may play an important role in the process of HBV-related liver failure and can be an important prognostic marker.

This study aimed to assess and compare the immediate stress and psychological impact experienced by people with and without psychiatric illnesses during the peak of 2019 coronavirus disease (COVID-19) epidemic with strict lockdown measures. Seventy-six psychiatric patients and 109 healthy control subjects were recruited from Chongqing, China and completed a survey on demographic data, physical symptoms during the past 14 days and a range of psychiatric symptoms using the Impact of Event Scale-Revised (IES-R), Depression, Anxiety and Stress Scale (DASS-21) and Insomnia Severity Index (ISI). IES-R measures PTSD symptoms in survivorship after an event. DASS-21 is based on tripartite model of psychopathology that comprise a general distress construct with distinct characteristics. The mean IES-R, DASS-21 anxiety, depression and stress subscale and ISI scores were higher in psychiatric patients than healthy controls (p

We study the employment of an adopted optics system for the reduction of thermal blooming effects by the phase correction of a 1.064 μm laser. The energy concentration of the beam spot in the farfield substantially increases if the adaptive optics system is performed in a closed loop. The phase compensation of the adapted optics system is effective for a Bradley–Hermann distortion number of less than 130. The experimental results obtained are in good agreement with the simulation results. This study provides many physical explanations and important conclusions for using adaptive optics to reduce the thermal blooming effect.

Objective. To investigate the relationships between sex hormone-binding globulin (SHBG) and comprehensive metabolic parameters including biometric, glycemic, lipid, liver, and renal functions of women with polycystic ovary syndrome (PCOS). Study Design and Methods. A total of 1000 women diagnosed as PCOS by modified Rotterdam criteria were enrolled in a randomized controlled trial. SHBG and comprehensive metabolic parameters were measured at the baseline visit. Metabolic parameters included biometric parameters, glucose and lipid panels, and liver and renal function parameters. An independent t-test and linear regression were performed to investigate the associations between SHBG and metabolic parameters. Logistic regression was used to detect the relationship between SHBG and the presence of metabolic syndrome. Results. In comparative analyses, PCOS women with lower SHBG levels had higher body mass index, waist circumference, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, systolic and diastolic blood pressure, triglycerides, apolipoprotein B (APOB), low-density lipoprotein (LDL), aspartate transferase (AST), alanine transferase (ALT), and blood urea nitrogen (BUN), but lower high-density lipoprotein (HDL) and apolipoprotein A1 (APOA1). In linear regression, SHBG was inversely associated with waist circumference, systolic blood pressure, triglyceride, LDL, APOB, ALT, AST, and BUN but positively associated with HDL and APOA1 after adjusting the BMI. In logistic regression, SHBG is a protective predictor for metabolic syndrome (odds ratio = 0.96; 95% confidence interval: 0.95–0.97). The area under the receiver-operator characteristic curve is 0.732 with a 95% confidence interval of 0.695–0.770. SHBG Conclusions. Lower SHBG was associated with worsening biometric, lipid, liver, and renal functions but not glycemic parameters among women with PCOS. SHBG can be used as a tool to screen metabolic syndrome. This trial is registered with NCT01573858 and ChiCTR-TRC-12002081.

When training base classifier by ternary Error Correcting Output Codes (ECOC), it is well know that some classes are ignored. On this account, a non-competent classifier emerges when it classify an instance whose real label does not belong to the meta-subclasses. Meanwhile, the classic ECOC dichotomizers can only produce binary outputs and have no capability of rejection for classification. To overcome the non-competence problem and better model the multi-class problem for reducing the classification cost, we embed reject option to ECOC and present a new variant of ECOC algorithm called as Reject-Option-based Re-encoding ECOC (ROECOC). The cost-sensitive classification model and cost-loss function based on Receiver Operating Characteristic (ROC) curve are built respectively. The optimal reject threshold values are obtained by combing the condition to be met for minimizing the loss function and the ROC convex hull. In so doing, reject option (t1, t2) provides a three-symbol output to make dichotomizers more competent and ROECOC more universal and practical for cost-sensitive classification issue. Experimental results on two kinds of datasets show that our scheme with low-degree freedom of initialized ECOC can effectively enhance accuracy and reduce cost.

Photovoltaic (PV) air conditioning (AC) is an effective way to solve the problems of energy consumption of office buildings. In this study, a set of parameters were designed for PV AC, including PV capacity, AC parameter, and inverter parameter. Then, the parameters were applied to a 20-m2 office building, and a PV AC system test platform was built. The test lasted for one year; the corresponding data including typical daily data and annual data were collected and analyzed. The results show that the PV AC system quickly decreases or increases the room temperature by ~9.5% and 17% in 1 h of cooling and heating periods, respectively, thus maintaining the room temperature within the set temperature range of ±0.9 °C. The data also show that by proper design of parameters, a PV AC system can satisfy the electricity demand of AC. In the cooling period, heating period, and annual operation conditions, the PV system provided 114%, 73%, and 188% of the energy for the AC system, respectively. Next, economic calculations show that PV AC is suitable for office buildings. The local payback period is only 7.5 years; both the energy saving and emission reduction are significant.

Background and Purpose— Circulating levels of SHBG (sex hormone-binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain whether low SHBG is prospectively predictive of stroke risk, particularly in women. We investigated whether SHBG is associated with risk of incident ischemic stroke (IS) among women in the WHI (Women’s Health Initiative). Methods— From an observational cohort of 161 808 postmenopausal women enrolled in the WHI at 40 sites across the United States from 1993 to 1998, we identified 13 192 participants free of prevalent stroke at baseline who were included in an ancillary study that measured serum SHBG. We used Cox proportional hazards regression, stratified by SHBG measurement assay, to assess IS risk across quintiles of SHBG (Q1–Q5), adjusting first for demographic variables (model 1), additionally for body mass index, hypertension, alcohol use, and smoking status (model 2), and for physical activity and reproductive risk factors (model 3). In sensitivity analyses, potential mediators (diabetes mellitus status, levels of estradiol, testosterone, and CRP [C-reactive protein]) were included. Results— Of 13 192 participants (mean age, 62.5 years; 67.4% non-Hispanic white, 18.5% black, 7.6% Hispanic, and 5.0% Asian), after following for an average of 11.6 years, 768 IS events were adjudicated. Compared with the highest quintile of SHBG levels (referent), women in the lowest SHBG quintile had a higher risk of IS in all 3 multivariable models (model 1: hazard ratio, 1.88 [95% CI, 1.47–2.41]; model 2: hazard ratio, 1.69 [95% CI, 1.30–2.20]; model 3: hazard ratio, 1.61 [95% CI, 1.19–2.19]; trend tests P Conclusions— In this prospective cohort of postmenopausal women, there was a statistically significant inverse association between serum SHBG levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.

Background Chancre self-healing is an important clinical feature in the early stages of syphilis infection. Wound healing may involve an important mechanism by the migration of fibroblasts filling the injured lesion. However, the specific mechanism underlying this process is still unknown. Objectives We aimed to analyse the role of Tp0136 in the migration of fibroblasts and the related mechanism. Methods The migration ability of fibroblasts was detected by a wound-healing assay. RT-PCR and ELISA detected the expression of MCP-1, IL-6 and MMP-9. TLR4 expression was detected by RT-PCR. The protein levels of CCR2 and relevant signalling pathway molecules were measured by Western blotting. Results Tp0136 significantly promoted fibroblast migration. Subsequently, the levels of MCP-1 and its receptor CCR2 were increased in this process. The migration of fibroblasts was significantly inhibited by an anti-MCP-1 neutralizing antibody or CCR2 inhibitors. Furthermore, studies demonstrated that Tp0136 could activate the ERK/JNK/PI3K/NF-κB signalling pathways through TLR4 activity and that signalling pathways inhibitors could weaken MCP-1 secretion and fibroblast migration. Conclusions These findings demonstrate that Tp0136 promotes the migration of fibroblasts by inducing MCP-1/CCR2 expression through signalling involving the TLR4, ERK, JNK, PI3K and NF-κB signalling pathways, which could contribute to the mechanism of chancre self-healing in syphilis.

The development of Internet of Things (IoT) dramatically facilitates the integration of computing systems with the physical world. However, as IoT devices are more easy to compromise than desktop computers, cybercriminals have founded IoT-based botnets to launch Distributed Denial of Service (DDoS) attacks with unprecedented traffic volume. To mitigate the damages associated with these attacks, the detection of IoT-based botnet has to preempt the command and control (C&C) communication to prevent the delivery of the attack codes. Motivated by the extensively implementation of domain generation algorithm in botnets, in this article, we propose ConnSpoiler, a lightweight system that detects IoT-based botnets by identifying the stream of algorithmically generated domains (AGDs) in a fast way. ConnSpoiler only needs negligible system resources to take effect and thus can execute well on the resource-restraint IoT devices. By outfitting a powerful statistical algorithm, i.e., threshold random walk, ConnSpoiler has a high probability (about 94%) of detecting infection before the compromised devices connect C&C servers, which can help to prevent the succeeding attacks. Moreover, ConnSpoiler only requires the benign domains to take effect and therefore does not need extra effort to label malicious samples for training phase. We evaluate ConnSpoiler based on real-world DNS traffics collected from two different large ISP networks and show that it accurately identifies devices that are compromised by unknown botnets.

While Internet-of-Things (IoT) significantly facilitates the convenience of people's daily life, the lack of security practice raises the risk of privacy-sensitive user data leakage. Securing data transmission among IoT devices is therefore a critical capability of IoT environments such as Intelligent Connected Vehicles, Smart Home, Intelligent City and so forth. However, cryptographic communication scheme is challenged by the limited resource of low-cost IoT devices, even negligible extra CPU usage of battery-powered sensors would result in dramatical decrease of the battery life. In this paper, to minimize the resource consumption, we propose a communication protocol involving only the symmetric key-based scheme, which provides ultra-lightweight yet effective encryptions to protect the data transmissions. Symmetric keys generated in this protocol are delegated based on a chaotic system, i.e., Logistic Map, to resist against the key reset and device capture attacks. We semantically model such protocol and analyze the security properties. Moreover, the resource consumption is also evaluated to guarantee runtime efficacy.

With the decreasing reserves of fossil energy and the increasing capacity of renewable energy generation, the scale of microgrid based on distributed generations is expanding. However, more operation data and transaction information of microgrids will also bring several problems: the sufficient capacity of the server in the central management needed, the crises of trust among members, the transparency of transaction information and the confidentiality of data storage. In this paper, blockchain technology is used to deal with these problems as distributed data storage technology. A double-layer framework of energy transactions based on blockchain in multi-microgrids is proposed to provide decentralized trading, information transparency and mutual trust system of each node in the trading market. The central node within the microgrid collects the demand information of the trading market in lower layer and sends them to the trading market of multi-microgrids in higher layer to seek the energy transaction. The continuous double auction mechanism is used in the trading market to guarantee free and fair transactions among nodes. The proposed transaction framework effectively reduces the transaction volume with the main grid which improves energy utilization. Comprehensive simulation results are presented to prove the feasibility of the proposed transaction framework. This work was supported in part by the National Natural Science Foundation of China under Grant 51907031, in part by the Department of Education of Guangdong Province: New and Integrated Energy System Theory and Technology Research Group under Grant 2016KCXTD022, in part by the Operation Fund of Guangdong Key Laboratory of Clean Energy Technology under Grant 2017B030314127, and in part by the Brunel Research Initiative and Enterprise Fund (BRIEF).

Objective To provide an analysis of Web of Science (WoS) indexed literature related to stem cells therapy in spinal cord injury published between 1999 and 2018. Methods Data were obtained from the WoS Core Collection on March 30, 2019. Qualitative and quantitative analysis was conducted based on WoS. Co-citation analysis, collaboration analysis, and co-words analysis of keywords was conducted by using CiteSpace. Results A total of 4188 references were obtained. The number of publications continually increased over the investigated period. Articles were the most frequently document type. Cell Transplantation (127) was the most productive journal. Experimental Neurology (2180) was the most frequently co-cited journal. H. Okano was the most productive and influential author, with 98 publications and 4860 cited counts. The most productive country and institution were the United States and University of Toronto, respectively. Researchers and institutions from Canada, the United States, Japan, and China were the core research forces. There was a broad and close cooperation worldwide. The Lu et al.‘s (2012) article (co-citation counts, 177) was the most representative and symbolic reference. Transplantation, functional recovery, marrow-derived mesenchymal stem cell treatment, and progenitor cells were the hot spots. Inflammation, glial scar, nerve regeneration, neurite outgrowth, and bone marrow stromal cell were research frontiers. Conclusions Research on stem cells for spinal cord injury is a well-developed and promising research field. There is broad global scientific research cooperation. More cooperation among top authors, institutions, and countries is needed. Our results may be helpful for researchers in identifying further potential perspectives on collaborators, research frontiers, and hot topics.

What is known and objective Personalized treatment with tacrolimus has remained a challenge. The present study aimed to evaluate the potential of an integrative approach to predict individual tacrolimus concentrations and dosages based on endogenous CYP3A4 phenotype, CYP3A5 genotype and clinical variables. Methods A random forest (RF) algorithm which incorporated an endogenous CYP3A4 phenotype (assessed by urinary ratio of 6β-hydroxycortisol and 6β-hydroxycortisone to cortisol and cortisone), CYP3A5*3 genotype and other clinical determinants of tacrolimus disposition was performed in 182 medically stable renal transplant recipients. Results and discussion The results suggested that endogenous CYP3A4 phenotype was the most important determinant of tacrolimus concentrations and dose requirements. RF models provided high goodness of fit (R2 ) with .92 and .95 for the prediction of tacrolimus trough concentrations and dosages, respectively, as well as high predictability (Q2 ) with 0.63 and 0.70, respectively. Significant correlations existed between experimental and predictive data. What is new and conclusion In summary, endogenous CYP3A4 phenotype is a critical biomarker for the determination of tacrolimus disposition. This predictive RF approach based on CYP3A4 biomarker with the combination of CYP3A5*3 genotype and other clinical variables can be used for predicting tacrolimus concentrations and dosages, which may serve as a useful tool in individualized tacrolimus dosing.

Background: The process of ubiquitylation, carried out by a three-step enzymatic cascade, maintains the balance of intracellular proteins and the stability of their functions. FBXW2 is a novel F-box protein, and acts as a tumor suppressor gene in lung cancer by directly degrading substrates or regulating the other E3 ligases. However, whether or how FBXW2 regulates prostate cancer (PCa) tumorigenesis and progression is still unclear.Methods: The expression levels of FBXW2 in PCa tissues and matched non-tumor tissues were detected by immunoblotting and qPCR. Cell counting kit-8, wound-healing assay, invasion assay, apoptosis and cell cycle assays, and animal experiments were performed to identify the function of FBXW2 in PCa cells. Half-life analysis, immunoprecipitation, and the in vivo ubiquitylation assay were performed to determine how FBXW2 regulates EGFR and its downstream signaling pathway.Results: FBXW2 expression was lowly expressed in highly-progressive PCa tissues and PCa cell lines. Augmented FBXW2 expression suppressed PCa cell progression and metastasis by repressing EGFR downstream proteins, while FBXW2 depletion had opposite effects. Overexpression of FBXW2 inhibited tumor growth, and even osteolytic bone destruction. Furthermore, FBXW2 and EGFR protein levels were inversely correlated in PCa cell lines and patient tumor tissues. EGFR protein level and its half-life was extended by FBXW2 depletion. While the basal level of EGFR was decreased, and its half-life was shortened upon overexpression of FBXW2-WT but not its dominant negative mutant. Intriguingly, FBXW2 promoted EGFR ubiquitylation and degradation via its binding motif (TSNNST) on EGFR, thereby elevated FBXW2 abrogated the PCa cell growth and metastasis caused by EGF stimulation.Conclusions: Collectively, our data shows that FBXW2 inhibits PCa cell progression and metastasis by promoting EGFR ubiquitylation and degradation, and would be a novel tumor suppressor for PCa.

Objective During the COVID-19 pandemic, some patients with novel coronavirus pneumonia may have concurrent disease that must be accepted surgery. However, the extensive inflammatory response existed in this population, especially in the lungs. And various ventilation could affect the inflammation of lungs. Therefore, how to choose the ventilation mode to reduce the effect of mechanical ventilation on inflammation is an important clinical practice. We aim to investigate the effect of different ventilation modes on inflammatory factor levels of patients undergoing surgery with COVID-19 through this systematic review and meta-analysis. Methods and analysis This systematic review and meta-analysis have been registered in the International Prospective Register of Systematic Reviews (PROSPERO). The PubMed, Embase via Ovid, Chinese Biological Medical Database (CBM), China National Knowledge Infrastructure (CNKI), the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from inception to date to find relevant studies. In addition, the relevant literature was also hand-searched. Two searchers independently selected the studies, extracted data and assessed the quality of studies included. The Review Manager 5.4 software (The Cochrane library,Oxford,England) will be used for data synthesis and meta-analysis. Continuous variables were embodied by Weight Mean Differences with 95% confidence intervals (CI). Dichotomous outcomes were embodied by Odds ratio with 95%CI. Ethics and dissemination Ethical approval is not required because the data was collected from the published studies. Finally, the results of this systematic review will be published in a peer-reviewed journal. PROSPERO registration number CRD42021251937

Objective To compare the clinical outcomes of transforaminal lumbar interbody fusion (TLIF) and endoscopic discectomy in the treatment of postoperative adjacent segment degeneration in patients with lumbar disc herniation (LDH). Methods From 2014 to 2017, 87 patients who were diagnosed with single-levelLDH and received surgery of TLIF (group X, n = 43) or endoscopic discectomy (group F, n = 44) were retrospectively analyzed. X-ray, MRI, CT and clinical symptoms were recorded before operation and at the last follow-up. The neurological function was originally evaluated by the Japanese Orthopaedic Association (JOA) score. Radiological evaluation included the height of intervertebral space (HIS), intervertebral foramen height (FH), intervertebral foramen area (FA), lumbar lordosis (CA) and intervertebral disc degeneration Pfirrmann score.Results There was no significant difference in average operation age, JOA improvement rate, reoperation rate and complications between the two groups. The average blood loss, average hospital stays and average operation time in group F were lower than those in group X. During the last follow-up, HIS, CA and FA decreased in both groups, and the changes in group X were more significant than those in group F (P < 0.05). There was no significant difference in postoperative FH between the two groups, but it decreased more in group X (P < 0.05).Conclusion Both TLIF and endoscopic surgery can achieve good results in the treatment of LDH, but the risk of lumbar adjacent segment degeneration after intervertebral foraminal surgery is lower.

Esophageal cancer is the fourth primary cause of cancer-related death in the male in China.The cornerstone of treatment for resectable esophageal cancer is surgery. With the development of minimally invasive esophagectomy (MIE), it is gradually adopted as an alternative to open esophagectomy (OE) in real-world practice. The purpose of this study is to explore whether MIE vs. OE will bring survival benefits to patients with the advancement of treatment techniques and concepts. Methods Data were obtained from the Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database (SCH-ECCM Database). We retrospective analyzed esophageal cancer patients who underwent esophagectomy from Jan. 2010 to Nov. 2017. Patients were divided into two groups: MIE and OE groups. Clinical outcome and survival data were compared using TNM stages of AJCC 8th edition. Results After 65.3 months of median follow-up time, 2958 patients who received esophagectomy were included. 1106 of 2958 patients (37.4%) were underwent MIE, 1533 of 2958 patients (51.8%) were underwent OE. More than half of the patients (56.7%, 1673/2958) were above stage III. The median overall survival (OS) of 2958 patients was 51.6 months (95% CI 45.2–58.1). The MIE group's median OS was 74.6 months compared to 42.4 months in the OE group (95% CI 1.23–1.54, P Conclusion The nearly 8-year follow-up data from this single cancer center suggests that with the advancement of minimally invasive surgical technology, MIE can bring significant benefits to patients' long-term survival compared with OE. Following the continuous progression of minimally invasive surgery and establishing a mature surgical team, MIE should be encouraged.

Background: Some have speculated that LSTV has an impact on lumbar curve. A retrospective study was conducted to evaluate S-line as predictor of clinical outcome for patients undergone transforaminal lumbar interbody fusion for lumbar spinal stenosis.Methods: 126 patients undergoing transforaminal lumbar interbody fusion were enrolled. S-line stands for the connecting line between the highest points of the iliac crests on both sides. The patients were divided into two groups according to the position of S-line, S-line (-) group included patients whose S-line were between L4 and L5, and S-line (+) group included patients whose S-line is above or below this range, which were divided into two subgroups. Their pre-operative imaging data about sagittal alignment were collected, including lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI) and pelvic tilt (PT). Clinical outcomes were measured using Japanese Orthopaedic Association (JOA) scores, the Oswestry disability index (ODI), visual analog scale (VAS) before the surgery and postoperatively. The correlation of S-line and clinical outcomes, as well as sagittal alignment and clinical outcomes, were analyzed.Results: LL, SS, PI, PT and PI minus(-) LL of S-line (-) group were (45.39°±12.68°), (30.27°±10.55°), (43.32°±12.22°), (13.05°±6.52°), (-2.07°±8.20°), respectively, and those parameters of S-line (+) group were (40.29±14.92), (35.70°±14.09°), (52.59°±17.07°), (16.89°±8.24°), (12.30°±9.98°), respectively. Significant difference were seen in the above parameters between S-line (-) and S-line (+) group. For S-line (-) and S-line (+) group, post-operative JOA score were (22.39±2.12), (20.26±2.46), post-operative VAS were (2.07±0.88), (3.14±1.47), the post-operative ODI were (8.36±3.28), (11.82±3.32), the improvement rate is (0.61±0.13), (0.55±0.15), Significant differences of those parameters are seen between S-line (-) group and S-line (+) group.Conclusion: S-line is a reliable predictor of clinical outcome for patients undergone transforaminal lumbar interbody fusion for lumbar spinal stenosis.

Image processing is widely used in intelligent robots, significantly improving the surveillance capabilities of smart buildings, industrial parks, and border ports. However, relying on the camera installed in a single robot is not enough since it only provides a narrow field of view as well as limited processing performance. Specially, a target person such as the suspect may appear anywhere and tracking the suspect in such a large-scale scene requires cooperation between fixed cameras and patrol robots. This induces a significant surge in demand for data, computing resources, as well as networking infrastructures. In this work, we develop a scalable architecture to optimize image processing efficacy and response rate for visual ability. In this architecture, the lightweight pre-process and object detection functions are deployed on the gateway-side to minimize the bandwidth consumption. Cloud-side servers receive solely the recognized data rather than entire image or video streams to identify specific suspect. Then the cloud-side sends the information to the robot, and the robot completes the corresponding tracking task. All these functions are implemented and orchestrated based on micro-service architecture to improve the flexibility. We implement a prototype system, called Rinegan, and evaluate it in an in-lab testing environment. The result shows that Rinegan is able to improve the effectiveness and efficacy of image processing.

Aim: To detect predictive value of preconception or early pregnancy sex hormone-binding globulin (SHBG) for subsequent gestational diabetes mellitus (GDM). Materials & methods: We searched Embase, Medline, PubMed, Web of Science and Cochrane library up to January 2020. Studies assessing diagnostic performance of SHBG for GDM diagnosed by well-defined diagnostic criteria using oral glucose tolerance test. Results: Totally seven studies with 1947 women were included and 247 were diagnosed as GDM. SHBG had a combined diagnostic odds ratio of 6.68 (95% CI: 4.58–9.74), sensitivity of 0.70 (95% CI: 0.51–0.84), specificity of 0.74 (95% CI: 0.52–0.88), positive likelihood ratio of 2.49 (95% CI: 1.73–3.57) and negative likelihood ratio of 0.37 (95% CI: 0.23–0.61). The area under the summary receiver operating characteristic curve was 0.78 (95% CI: 0.74–0.82). Conclusion: SHBG had a predictive value for GDM and might improve GDM screening. However, heterogeneity between studies warrants more research into this topic.

ObjectiveThis article aimed to investigate whether serum magnesium is associated with insulin resistance index and testosterone level in women with polycystic ovary syndrome (PCOS).Materials and MethodsOverall 1000 women with PCOS were enrolled in a randomized controlled trial and a cross-sectional analysis of the association of serum magnesium with glucose metabolism markers and testosterone was performed. Serum magnesium, glucose metabolism markers and testosterone were measured. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Multivariable linear regression and logistic regression models were used to estimate the association between serum magnesium, insulin resistance and testosterone.ResultsIn comparative analyses, women with higher quartile of serum magnesium had significantly lower fasting glucose, HOMA-IR and testosterone. Multiple linear regression showed serum magnesium was independently negatively associated with insulin, glucose, HOMA-IR, testosterone and positively associated with QUICKI (P for trend ConclusionThe current findings suggest that lower serum magnesium was associated with aggravated insulin resistance and higher testosterone levels among women with PCOS.

Objectives: This study aimed to evaluate the level and factors affecting the perioperative exercise intention in China.Design: This study was a cross-sectional survey in Southwest China.Methods: Four hundred and ninety nine participants were randomly sampled in eight medical centers from November 23, 2020 to November 27, 2020. The survey included sociodemographic information and a 24-item modified questionnaire, which aimed to evaluate the attitude toward daily exercise, perception of perioperative exercise, social support and the perioperative exercise intention. A multivariable linear regression model was used to evaluate the effect of different items on the patients' intention for perioperative exercise.Results: A total of 523 responses (95.09%) were collected and 499 (95.41%) were analyzed. The level of exercise intention of the patients during the perioperative period was: 14.83% planned to exercise every day in the hospital, 21.04% planned to exercise every other day, and 35.87% planned to exercise every week. Intensity of daily exercise (P = 0.016), positive attitude of daily exercise (P < 0.001), positive attitude of perioperative exercise (P < 0.001) and social support (P < 0.001) were positively associated with the intention for perioperative exercise. Female (P = 0.012), non-tertiary center (P = 0.011), and preoperative anxiety (P = 0.023) was negatively associated with it.Conclusions: The intention for perioperative exercise was low in Southwest China. The authors aimed to relieve preoperative anxiety, promote the education of perioperative exercise, design perioperative exercise programs, and provide more social support from medical staff and family for inpatients undergoing elective surgery.

Ethnopharmacological relevance ‘Ershiwuwei Shanhu’ Pill (ESP) is a classic Tibetan medicine to treat neurological disorders in nervous system, especially for neurological pains and epilepsy. It contains many Tibet-specific mineral medicines, among which Halloysite (Halloysitum rubrum, HR) was regarded as the main active one. As mineral medicines contain heavy metals with poor solubility, the doubts about its safety restricted its clinical application and further development. Aim of the study A 7-day acute toxicity of ESP and its main active mineral medicine HR was systematically studied for investigating the safety of ESP and exploring the role of HR in ESP's potential toxicity. Materials and methods In this study, the acute oral toxicity assessment of formula-ESP and HR were performed on rats for 7 days at doses equivalent to 10 (1 g/kg) and 40 times (4 g/kg) the typical clinical dose (0.1 g/kg). 1H NMR based metabolomics profiling, aided with biochemical analysis and histopathology, was conducted to explore the global metabolic changes in the livers and kidneys of the administrated rats. Results High-dose HR caused oxidative stress, energy metabolism disorders, purine metabolism impairments and amino acid metabolism imbalance in rats, resulting in hepatotoxicity and nephrotoxicity, which in accordance with the increased biochemical index in blood (ALT, AST, BUN and CRE). ESP (low-dose) induced metabolites changes were far more less than HR in livers, showcasing the distinct advantage of formula in reducing toxicity. Furthermore, low-dose ESP disturbed renal metabolism in a way similar to high-dose HR, which implies that HR might be the major source of the potential nephrotoxicity of ESP. Conclusion HR exhibited potential hepatoxicity and nephrotoxicity, but the formula- ‘Ershiwuwei Shanhu’ Pill which contains HR is considered relatively safe.

Aims/Introduction Metformin, a widely prescribed antidiabetic agent, has been shown to exhibit anti‐inflammatory effects in obese and type 2 diabetes patients, but the mechanism is not well elucidated. Microribonucleic acids (miRNAs) are a group of small non‐coding ribonucleic acids that participate in many biological and pathological processes. The aim of the present study was to investigate whether Dicer, a key miRNA biogenesis enzyme, and miRNAs in macrophages are implicated in the anti‐inflammatory effects of metformin. Materials and Methods Enzyme‐linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were carried out to verify the anti‐inflammatory effects of metformin. miRNA microarray was applied to detect the expression profile of miRNA. Western‐blotting, enzyme‐linked immunosorbent assay and reverse transcription quantitative polymerase chain reaction were used to examine the role Dicer and miRNAs play in the anti‐inflammatory effects of metformin. Results In parallel with the suppression of interleukin‐6 and tumor necrosis factor‐α production in resting and lipopolysaccharide‐stimulated macrophages, metformin could induce an increase in Dicer and most miRNAs. When Dicer was knocked down, the anti‐inflammatory effects of metformin were significantly attenuated. Additionally, the upregulation of miRNA (miR)‐34a‐5p and miR‐125b‐5p by metformin were also blunted in Dicer knockdown macrophages. Furthermore, inhibition of miR‐34a‐5p and miR‐125b‐5p could impair the suppressive action of metformin on pro‐inflammatory factors production, whereas overexpression of the two miRNAs mimicked the anti‐inflammatory effects of metformin. Conclusions Metformin might show anti‐inflammatory effects in macrophages through the induction of Dicer and the subsequent upregulation of miR‐34a‐5p and miR‐125b‐5p., Metformin, a widely used antidiabetic drug, has been reported to reduce inflammatory markers in obese patients and patients with diabetes, but the mechanism is not well elucidated. In the present study, we report that metformin inhibits pro‐inflammatory factors production in resting and lipopolysaccharide‐stimulated macrophages through the induction of Dicer and the subsequent upregulation of microribonucleic acid‐34a‐5p and microribonucleic acid‐125b‐5p. Our finding provides a novel mechanism of metformin against inflammation, and might be helpful in identifying potential therapeutic targets for inflammation‐associated diseases.

OBJECTIVE: “Just-in-time” (JIT) interventions delivered via smartphones have considerable potential for reducing HIV-risk behavior by providing pivotal support at key times prior to sex. However, these programs depend on a thorough understanding of when risk behavior is likely to occur to inform the timing of JITs. It is also critical to understand the most important momentary risk factors that may precede HIV-risk behavior, so that interventions can be designed to address them. Applying machine learning (ML) methods to ecological momentary assessment data on HIV-risk behaviors can help answer both questions. METHODS: Eighty HIV-negative men who have sex with men (MSM) who were not on PrEP completed a daily diary survey each morning and an experience sampling survey up to six times per day via a smartphone application for 30-days. RESULTS: Random forests models achieved the highest area under the curve (AUC) values for classifying high-risk condomless anal sex (CAS). These models achieved 80% specificity at a sensitivity value of 74%. Unsurprisingly, the most important contextual risk factors that aided in classification were participants’ plans and intentions for sex, sexual arousal, and positive affective states. CONCLUSIONS: Findings suggest that survey data collected throughout the day can be used to correctly classify about four of every five high-risk CAS events, while incorrectly classifying one of every five days as involving high-risk CAS when no such event occurred. A unique set of risk factors also often emerge prior to high-risk CAS events that may be useful targets for JITs.

This paper presents Granger mediation analysis, a new framework for causal mediation analysis of multiple time series. This framework is motivated by a functional magnetic resonance imaging (fMRI) experiment where we are interested in estimating the mediation effects between a randomized stimulus time series and brain activity time series from two brain regions. The independent observation assumption is thus unrealistic for this type of time-series data. To address this challenge, our framework integrates two types of models: causal mediation analysis across the mediation variables, and vector autoregressive (VAR) models across the temporal observations. We use "Granger" to refer to VAR correlations modeled in this paper. We further extend this framework to handle multilevel data, in order to model individual variability and correlated errors between the mediator and the outcome variables. Using Rubin's potential outcome framework, we show that the causal mediation effects are identifiable under our time-series model. We further develop computationally efficient algorithms to maximize our likelihood-based estimation criteria. Simulation studies show that our method reduces the estimation bias and improves statistical power, compared with existing approaches. On a real fMRI data set, our approach quantifies the causal effects through a brain pathway, while capturing the dynamic dependence between two brain regions.

Progesterone elevation (PE) on the day of hCG trigger is associated with decreased pregnancy outcome in fresh cycles. Evidence for this comes from overall patient estimates that mostly ignore different ovarian responses. To compare the impacts of PE on the day of hCG trigger on live birth rates (LBs) in low, intermediate and high ovarian responders and to explore the cut-off value for PE in different populations according to the ovarian response, we retrospectively analyzed a total of 2,351 patients receiving fresh assisted reproduction technology (ART) transfer cycles with GnRH agonist using a long or short protocol. Trend and multivariate logistic regression analyses were performed to identify the cutoff values of PE and to evaluate the effects of PE on LB rates (LBRs) in different ovarian responders. The study found that PE has a detrimental effect on LBRs in low to intermediate ovarian responders rather than in high responders. The cut-off values for PE were 1.0 ng/mL and 2.0 ng/mL for low and intermediate ovarian responders, respectively. The different associations between PE and LBRs according to ovarian response could more accurately predict the prognosis of the IVF cycle and could be used to optimize the treatment of patients undergoing In Vitro Fertilization (IVF)/ Intracytoplasmic Sperm Injection (ICSI).

Proton pump inhibitors (PPIs) are commonly used to lessen symptoms in patients with gastroesophageal reflux disease (GERD). However, the effects of PPI therapy on the gastrointestinal microbiota in GERD patients remain unclear. We examined the association between the PPI usage and the microbiota present in gastric mucosal and fecal samples from GERD patients and healthy controls (HCs) using 16S rRNA gene sequencing. GERD patients taking PPIs were further divided into short-term and long-term PPI user groups. We showed that PPI administration lowered the relative bacterial diversity of the gastric microbiota in GERD patients. Compared to the non-PPI-user and HC groups, higher abundances of Planococcaceae, Oxalobacteraceae, and Sphingomonadaceae were found in the gastric microbiota from the PPI-user group. In addition, the Methylophilus genus was more highly abundant in the long-term PPI user group than in the short-term PPI-user group. Despite the absence of differences in alpha diversity, there were significant differences in the fecal bacterial composition of between GERD patients taking PPIs and those not taking PPIs. There was a higher abundance of Streptococcaceae, Veillonellaceae, Acidaminococcaceae, Micrococcaceae, and Flavobacteriaceae present in the fecal microbiota from the PPI-user group than those from the non-PPI-user and HC groups. Additionally, a significantly higher abundance of Ruminococcus was found in GERD patients on long-term PPI medication than that on short-term PPI medication. Our study indicates that PPI administration in patients with GERD has a significant effect on the abundance and structure of the gastric mucosal microbiota but only on the composition of the fecal microbiota. Keywords: Microbiota, Gastroesophageal reflux disease, Proton pump inhibitors, Gastric mucosal, Fecal

Background Local anesthetics in spinal anesthesia have neurotoxic effects, resulting in severe neurological complications. Intrathecal monosialoganglioside (GM1) administration has a therapeutic effect on bupivacaine-induced neurotoxicity. The aim of this study was to determine the underlying mechanisms of bupivacaine-induced neurotoxicity and the potential neuroprotective role of GM1. Materials and methods A rat spinal cord neurotoxicity model was established by injecting bupivacaine (5%, 0.12 μL/g) intrathecally. The protective effect of GM1 (30 mg/kg) was evaluated by pretreating the animals with it prior to the bupivacaine regimen. The neurological and locomotor functions were assessed using standard tests. The histomorphological changes, neuron degeneration and apoptosis, and endoplasmic reticulum stress (ERS) relevant markers were analyzed using immunofluorescence, quantitative real-time PCR, and Western blotting. Results Bupivacaine resulted in significant neurotoxicity in the form of aberrant neurolocomoter functions and spinal cord histomorphology and neuronal apoptosis. Furthermore, the ERS specific markers were significantly upregulated during bupivacaine-induced neurotoxicity. These neurotoxic effects were ameliorated by GM1. Conclusion Pretreatment with GM1 protects against bupivacaine-induced neurotoxicity via the inhibition of the GRP78/PERK/eIF2α/ATF4-mediated ERS.