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Background We conducted a meta-analysis to evaluates the incidence of the gastrointestinal (GI) adverse events with the use of PD-1 inhibitors among patients with advanced non-small cell lung cancer (NSCLC). Methods The PICOs (participants, intervention, comparison, and outcomes) elements were used for the selection of studies to meet the inclusion and exclusion criteria. Google Scholar, PubMed, Science Direct and proceedings of major oncology conferences were systematically searched from their inception to December 2020, to identify studies which reported the GI adverse events of PD-1 inhibitors among patients with NSCLC. Risks of bias were assessed by using a revised methodological index for nonrandomized studies (MINORS). Pooled incidences and weighted relative risk (RR) estimate for GI adverse events, the incidence of treatment discontinuation due to GI adverse events was also calculated. To perform the analysis of qualified studies, the model of random effects was used and the inconsistency of studies with the I2 index was investigated. OpenMeta 10.10, Stata 11.0 and RevMan 5.3 software were used for data analysis. Results The research included 15 studies comprising of a total of 3,716 patients. The incidences of all-grade GI symptoms were: diarrhea 8.6% (95% CI: 6.6–10.6%), nausea 9.2% (95% CI: 7.3–11.0%), vomiting 3.2% (95% CI: 1.9–4.5%), constipation 2.8% (95% CI: 1.8–3.9%), colitis 0.7% (95% CI: 0.4–1.1%), stomatitis (95% CI: 1.0–2.7%), and decreased appetite 10.0% (95% CI: 8.3–11.7%). Therapy using PD-1 inhibitors was discontinued in 2.5% (95% CI: 0.0–5.1%) of patients with nausea, in 3.0% (95% CI: 0.7–5.3%) of those with diarrhea, and in 45.7% (95% CI: 20.6–70.7%) of patients with colitis. Compared with chemotherapy, the use of PD-1 inhibitors showed significant increase in the occurrence of grade 1–4 colitis (RR =3.90, 95% CI: 1.41–10.81, P=0.009) and grade 3–4 colitis (RR =3.76, 95% CI: 1.07–13.26, P=0.04). Discussion This meta-analysis provides a reliable estimate of the incidences of GI adverse events among NSCLC patients. Especially when colitis does occur, it often results in therapy discontinuation. Use of PD-1 inhibitors led to a higher incidence of colitis as compared to the use of chemotherapy.

Background Persistent infection by high-risk human papillomavirus (HPV) is the leading cause of cervical intraepithelial neoplasia and cervical carcinoma. Local hyperthermia at 44ºC has been proven efficacious to clear cutaneous or anogenital warts caused by HPV infection. This study aims to assess the effect of hyperthermia at 44ºC on the clearance of high-risk HPV. Methods A randomized, patient-blind, sham treatment–controlled trial was conducted in 4 medical centers. We enrolled patients with positive high-risk HPVs and normal or insignificant cytological findings (negative/atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion). Participants were randomly assigned (1:1) to receive either hyperthermia at 44ºC or 37ºC, for 30 minutes in each session. Patients in both groups received treatment once a day for 3 consecutive days, plus 2 more sessions 10 ± 3 days later. The primary outcome was clearance rate of HPV 3 months after treatment. Results After a 3-month follow-up, hyperthermia treatment at 44ºC and 37ºC achieved HPV clearance rates of 85.19% (23/27) and 50% (13/26), respectively (P = .014). There was no significant difference of treatment response between patients with single and multiple type of HPV by 44ºC hyperthermia treatment. There were no significant adverse events recorded during the treatment period in both groups. Conclusions Local hyperthermia at 44ºC safely and significantly aids in clearing cervical high-risk HPVs, the effect of which helps halt the progression of cervical transformation and transmission of the virus. Clinical Trials Registration NCT03436251.

This study evaluates the impact of the use of antibiotics on the effectiveness of nivolumab in the treatment of advanced/metastatic non-small cell lung cancer (NSCLC). A literature search was conducted in various electronic databases to identify studies, which evaluated the impact of antibiotic use on the survival of patients with advanced/metastatic NSCLC who have been treated with nivolumab. Six studies, comprising a total of 787 patients with 37.2% females and of age range 30–90 years, were included in the study. A lack of smoking history was reported in 14.4% of the patients. A meta-analysis was conducted in 678 and 713 patients for PFS and OS, respectively. The pooled HR was 1.95 (95% CI: 1.13–3.37, P = 0.016) for PFS and 2.70 (95% CI: 1.81–4.02, P < 0.001) for OS. Among patients exposed to antibiotics, the median PFS and OS were reduced by 1.6 months (95% CI: 1.5–1.7) and 8.8 months (95% CI: 8.5–9.1), respectively. Our study indicates that, among patients with advanced/metastatic NSCLC, the use of antibiotics with nivolumab led to a decrease in the median OS by more than 8 months. Studying the mechanism of the effect of antibiotics on the efficacy of nivolumab in patients with NSCLC should also be prioritized.

Purpose This study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes. Methods Arterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses. Results Compared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus. Discussion Cerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.

Prostate cancer is a serious threat to men's health worldwide. While previous studies have demonstrated that long non‑coding RNAs (lncRNAs) are closely associated with the initiation and development of several types of cancer, the role of lncRNAs in the progression of prostate cancer remains incompletely understood. In the present study, the lncRNA brain cytoplasmic RNA 1 (BCYRN1) was found to be overexpressed in prostate tumors compared with healthy tissues. Furthermore, the expression of BCYRN1 was found to be associated with Gleason score and lymph node metastasis. It was demonstrated that BCYRN1 silencing using small interfering RNA (siRNA) inhibited the proliferation of prostate cancer cells. The results of the present study indicated the presence of a reciprocal regulatory association between BCYRN1 and microRNA (miR)‑939‑3p. In addition, it was observed that BCYRN1 directly sponged miR‑939‑3p to upregulate histone deacetylase 11 (HDAC11) expression in prostate cancer cells. Moreover, transfection of recombinant HDAC11 reversed the inhibition of cell proliferation that was induced by BCYRN1 siRNA. A positive correlation between BCYRN1 and HDAC11 mRNA expression levels was also identified in prostate tumor and healthy tissues. Therefore, the findings of the present study may provide novel insight into the effects of lncRNAs on prostate cancer, and may enable the development of new therapeutic methods for patients with prostate cancer.

This study evaluates the efficacy of pembrolizumab for the treatment of advanced/metastatic melanoma. The literature search was conducted in electronic databases for studies that evaluated the efficacy and safety of pembrolizumab either alone or in combination with other treatments advanced/metastatic melanoma patients. Random-effects meta-analyses were performed to achieve pooled effect sizes of response and survival rates. The overall objective response rate (ORR) was 34.2% [95% confidence interval (CI): 30.4, 38.0]. However, ORR differed with respect to the history of prior systemic therapy. ORR was lower in studies with over 50% patients with prior therapy (25.5% [22.4, 28.5]) than in studies with under 50% patients with prior therapy (40.1% [34.1, 46.1]). ORR was higher in pembrolizumab monotherapy (32.9% [28.1, 37.7]) than in pembrolizumab–ipilimumab combination (27.6% [24.0, 31.2]). Overall ORR was inversely associated with visceral metastasis and prior systemic therapy. With pembrolizumab treatment, either alone or in combination, the progression-free survival (PFS) was 5.73 months; 12-, 24-, and 60-month PFS rate were 44%, 27%, and 25%, respectively; and 12-, 24-, and 60-month overall survival rates were 65%, 50%, and 41%, respectively. The percentage of AEs that led to treatment discontinuation was 13%. Pembrolizumab monotherapy is a valuable option for the treatment of advanced/metastatic melanoma patients.

Background Hyperthermia upregulates DNAJA4, a member of heat shock proteins (HSPs) 40 family, in human keratinocytes and HPV-infected tissue. DNAJA4 deficiency enhances growth arrest induced by hyperthermia. Clusterin (CLU) and phosphorylated ERK (p-ERK) play a role in regulating cell proliferation and apoptosis, under environmental stress. Objectives To examine the downstream molecules and signalling pathways of DNAJA4 and assess their roles in cell cycle and apoptosis of keratinocytes in response to hyperthermia. Methods Wild-type and DNAJA4-knockout (KO) HaCaT cells were exposed to either 44 °C (hyperthermia) or 37 °C (control) for 30 min. The expression levels of CLU and p-ERK were determined by RT-PCR and Western blotting. RNAi and PD98059 were used to inhibit the expression of CLU and p-ERK, respectively. Cell viability, cell cycle and apoptosis were analysed by MTS assay and flow cytometry. Fresh biopsy samples of human normal foreskin or condyloma acuminatum (CA) were utilized to examine the expression of CLU and p-ERK after ex vivo culture at 44 °C. Results The expression of CLU and p-ERK was significantly increased by hyperthermia treatment at 44 °C in HaCaT cells, foreskin and HPV-infected tissues. In HaCaT cells subjected to hyperthermia, DNAJA4 deficiency further augmented the expression of CLU and p-ERK. CLU deficiency enhanced the p-ERK expression. Hyperthermia-induced CLU and p-ERK exerted protective roles mainly through inhibiting apoptosis and maintaining cell cycle, respectively. Conclusions In keratinocytes, CLU and p-ERK are induced by hyperthermia, an effect which can be further enhanced by DNAJA4 deficiency. CLU deficiency also increases p-ERK expression. Both CLU and p-ERK are critical protective factors of human keratinocytes from hyperthermia-induced injury.

JavaScript engines have been shown prone to security vulnerabilities, which can lead to serious consequences due to their popularity. Fuzzing is an effective testing technique to discover vulnerabilities. The main challenge of fuzzing JavaScript engines is to generate syntactically and semantically valid inputs such that deep functionalities can be explored. However, due to the dynamic nature of JavaScript and the special features of different engines, it is quite challenging to generate semantically meaningful test inputs. We observed that state-of-the-art semantic-aware JavaScript fuzzers usually require manually written rules to analyze the semantics for a JavaScript engine, which is labor-intensive, incomplete and engine-specific. Moreover, the error rate of generated test cases is still high. Another challenge is that existing fuzzers cannot generate new method calls that are not included in the initial seed corpus or pre-defined rules, which limits the bug-finding capability. To this end, we propose a novel semantic-aware fuzzing technique named SoFi. To guarantee the validity of the generated test cases, SoFi adopts a fine-grained program analysis to identify available variables and infer types of these variables for the mutation. Moreover, an automatic repair strategy is proposed to repair syntax/semantic errors in invalid test cases. To improve the exploration capability of SoFi, we propose a reflection-based analysis to identify unseen attributes and methods of objects, which are further used in the mutation. With fine-grained analysis and reflection-based augmentation, SoFi can generate more valid and diverse test cases. Besides, SoFi is general in different JavaScript engines without any manual configuration (e.g., the grammar rules). The evaluation results have shown that SoFi outperforms state-of-the-art techniques in generating semantically valid inputs, improving code coverage and detecting more bugs. SoFi discovered 51 bugs in popular JavaScript engines, 28 of which have been confirmed or fixed by the developers and 10 CVE IDs have been assigned.

Diabetes is a global medical problem that causes many deaths every year. Complications caused by diabetes are serious and affect patients' quality of life. Diabetes mellitus erectile dysfunction (DMED) affects more than half of male diabetes patients. In this study, we determined the role of microRNA-874-3p (miR-874-3p) and nuclear protein-1 (Nupr1) in streptozocin-induced DMED rats. Control rats received equal amount of vehicle. These rats were also injected with lentiviral vector or agomir to silence or overexpress miR-874-3p or Nupr1. Apomorphine (100 μg/kg, s.c.) was used to induce erection and time of erection was recorded. Intracavernosal and mean arterial pressure ratio (ICP/MAP) were also recorded. O2- level and concentration of thiobarbituric acid reactive substances (TBARs) were detected using lucigenin-derived chemiluminescence method and Colorimetry. Rat cavernosum tissues were collected for subsequent experiments. Cavernosum smooth muscle cells (CSMCs) were also used for in vitro experiments. Nupr1 was found highly expressed (by RT-qPCR and Western blot analysis) in cavernosum tissues from DMED rats. Nupr1 silencing improved the ICP/MAP ratio and erection time. Nupr1 silencing also reduced CSMC apoptosis (by TUNEL assay) as well as decreased O2- level and TBAR concentration. Nupr1 was targeted and inhibited by miR-874-3p (by luciferase activity and RNA immunoprecipitation assays), which was downregulated in DMED. miR-874-3p downregulation was due to increased methylation at the promoter region (methylation-specific PCR). miR-874-3p overexpression improved erection time and reduced apoptosis. In summary, miR-874-3p was downregulated which led to increased apoptosis and erectile dysfunction in DMED rats, through inhibition of Nupr1-mediated pathway. This study may also provide a new therapeutic direction for the treatment of DMED.

Erectile dysfunction (ED) is a common comorbidity in males with diabetes. In this study, we aimed to investigate how lncRNA-MIAT affects ED in diabetes and the involved mechanism. Microarray analysis was performed to screen ED-related differentially expressed genes, regulatory microRNA (miR) and long noncoding RNA (lncRNA). Highly expressed lipoprotein lipase (LPL) was identified, and subsequently miR-328a-5p and lncRNA-MIAT were determined. Diabetes was induced by streptozotocin in rats, and diabetic rats with ED were selected. Vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were cocultured. The siRNA against lncRNA-MIAT, miR-328a-5p mimic and overexpression vector of LPL were transfected to investigate the specific effects of miR-328a-5p, lncRNA-MIAT and LPL on ED in diabetes. The expression of LPL, lncRNA-MIAT and miR-328a-5p in the serum of diabetic patients was measured. Increased LPL and lncRNA-MIAT and reduced miR-328a-5p were observed in diabetic patients. In addition, ED led to upregulated LPL and lncRNA-MIAT and downregulated miR-328a-5p in serum of diabetic patients and VSMCs of diabetic rats, especially in those with ED. LncRNA-MIAT directly regulated miR-328a-5p, which directly targeted LPL. LncRNA-MIAT upregulated LPL by acting as a ceRNA of miR-328a-5p. Silencing of lncRNA-MIAT and LPL or miR-328a-5p overexpression reduced VEC apoptosis and increased cell proliferation. In addition, an increased intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was noted in the corpus cavernosum of rats and inhibited VEC injury. Taken together, our data demonstrated that depleted lncRNA-MIAT suppressed LPL by increasing miR-328a-5p, thereby inhibiting VEC injury to attenuate ED in diabetic rats.

Gas pores on the top face of engine crankcases which are produced by Low Pressure Die Casting (LPDC) have been studied. Micrographic analysis has been conducted to investigate the evolution of such kind of casting defects. Results show that the surface of such casting defects have meandering shapes and random sizes. Microstructures of the cross section of the defects displayed folded feather shapes, which can be produced by the folded oxide film into the melt during the filling process. Oxide inclusions have been found below the filter at the ingate area. Thus, it is confirmed that the folded oxide films came from turbulence of the metal in the die cavity. Numerical simulation has been carried out to study the filling behavior of the crankcase. Results show that gating velocity suddenly increased when the liquid metal got into the waterfall structure and led to the turbulence. Moreover, the air entrained behavior is related with the gating velocity. With increasing gating velocity, turbulence happened when metal confluences, and became more intensely in the middle of the casting due to its waterfall structure. Finally, this kind of casting defect was confirmed as gas entrainment.

Codes of Open Source Software (OSS) are widely reused during software development nowadays. However, reusing some specific versions of OSS introduces 1-day vulnerabilities of which details are publicly available, which may be exploited and lead to serious security issues. Existing state-of-the-art OSS reuse detection work can not identify the specific versions of reused OSS well. The features they selected are not distinguishable enough for version detection and the matching scores are only based on similarity.This paper presents B2SMatcher, a fine-grained version identification tool for OSS in commercial off-the-shelf (COTS) software. We first discuss five kinds of version-sensitive code features that are trackable in both binary and source code. We categorize these features into program-level features and function-level features and propose a two-stage version identification approach based on the two levels of code features. B2SMatcher also identifies different types of OSS version reuse based on matching scores and matched feature instances. In order to extract source code features as accurately as possible, B2SMatcher innovatively uses machine learning methods to obtain the source files involved in the compilation and uses function abstraction and normalization methods to eliminate the comparison costs on redundant functions across versions. We have evaluated B2SMatcher using 6351 candidate OSS versions and 585 binaries. The result shows that B2SMatcher achieves a high precision up to 89.2% and outperforms state-of-the-art tools. Finally, we show how B2SMatcher can be used to evaluate real-world software and find some security risks in practice.

SOHO (small office/home office) routers provide services for end devices to connect to the Internet, playing an important role in cyberspace. Unfortunately, security vulnerabilities pervasively exist in these routers, especially in the web server modules, greatly endangering end users. To discover these vulnerabilities, fuzzing web server modules of SOHO routers is the most popular solution. However, its effectiveness is limited due to the lack of input specification, lack of routers’ internal running states, and lack of testing environment recovery mechanisms. Moreover, existing works for device fuzzing are more likely to detect memory corruption vulnerabilities.In this paper, we propose a solution ESRFuzzer to address these issues. It is a fully automated fuzzing framework for testing physical SOHO devices. It continuously and effectively generates test cases by leveraging two input semantic models, i.e., KEY-VALUE data model and CONF-READ communication model, and automatically recovers the testing environment with power management. It also coordinates diversified mutation rules with multiple monitoring mechanisms to trigger multi-type vulnerabilities. With the guidance of the two semantic models, ESRFuzzer can work in two ways: general mode fuzzing and D-CONF mode fuzzing. General mode fuzzing can discover both issues which occur in the CONF and READ operation, while D-CONF mode fuzzing focus on the READ-op issues especially missed by general mode fuzzing.We ran ESRFuzzer on 10 popular routers across five vendors. In total, it discovered 136 unique issues, 120 of which have been confirmed as 0-day vulnerabilities we found. As an improvement of SRFuzzer, ESRFuzzer have discovered 35 previous undiscovered READ-op issues that belong to three vulnerability types, and 23 of them have been confirmed as 0-day vulnerabilities by vendors. The experimental results show that ESRFuzzer outperforms state-of-the-art solutions in terms of types and number of vulnerabilities found.

As a notable chronic disorder, the incidence of interstitial cystitis (IC) has been documented to have increased among the female population with activity in microRNA-495 (miR-495) implicated in this disease. The current study was aimed at elucidating the effects associated with miR-495 on the inflammatory response and bladder fibrosis in rats with ulcerative IC via the JAK–STAT pathway by targeting JAK3. Ulcerative IC rat models were established. The targeting relationship between JAK3 and miR-495 was evaluated using luciferase reporter assay. After gain- or loss-of-function assays, mast-cell infiltration was assessed using toluidine blue staining, bladder fibrosis using Masson staining, and NO content using nitrate reductase method. JAK3 protein expression was detected by immunohistochemistry, JAK3, STAT1, STAT3, TGFβ-1, Col-I, Col-III, JAK1, JAK2, p-STAT1, and p-STAT3 expression by RT-qPCR and Western blot analysis, and serum IL-6, IL-8, IL-10, IL-17, and TNF-α levels in rats by ELISA. Following transfection of overexpressed miR-495 or siRNA-JAK3, a diminished degree of mast-cell infiltration, number of mast cells, bladder fibrosis, NO content, JAK3-positive expression, mRNA expression of JAK3, STAT1, STAT3, TGFβ-1, Col-I, Col-III, protein expression of JAK1, JAK2, JAK3, p-STAT1, p-STAT3, and expression of IL-6, IL-8, IL-10, IL-17, and TNF-α were identified. Collectively, our key findings provide evidence supporting the notion that the overexpression of miR-495 ameliorates inflammatory response and bladder fibrosis in ulcerative IC rat models via inactivation of the JAK–STAT signaling pathway by inhibiting JAK3.

The number of vulnerabilities increases rapidly in recent years, due to advances in vulnerability discovery solutions. It enables a thorough analysis on the vulnerability distribution and provides support for correlation analysis and prediction of vulnerabilities. Previous research either focuses on analyzing bugs rather than vulnerabilities, or only studies general vulnerability distribution among projects rather than the distribution within each project. In this paper, we collected a large vulnerability dataset, consisting of all known vulnerabilities associated with five representative open source projects, by utilizing automated crawlers and spending months of manual efforts. We then analyzed the vulnerability distribution within each project over four dimensions, including files, functions, vulnerability types and responsible developers. Based on the results analysis, we presented 12 practical insights on the distribution of vulnerabilities. Finally, we applied such insights on several vulnerability discovery solutions (including static analysis and dynamic fuzzing), and helped them find 10 zero-day vulnerabilities in target projects, showing that our insights are useful.

TrustScope is a new, a practical approach to identifying vulnerabilities in printer firmware without actually touching the firmware. By exploiting the trust between the firmware and the device drivers, TrustScope analyzes driver software to identify the driver endpoints that output the page description language (PDL) code to be sent to the printer, extracts key constraints for this output, generates new inputs violating these constraints, and fuzzes the printer firmware with malicious PDL code composed with these inputs yet conforming to the grammar of the PDL accepted by the printer. To accommodate the black-box nature of printers, printer behavior is observed strictly externally, allowing TrustScope to detect more vulnerabilities than only those that produce crashes. A variety of key optimizations, such as fuzzing without consuming paper and ink, and offline test case generation, make printer vulnerability detection feasible and practical. An implementation of TrustScope tested with 8 different printers reveals at least one test case causing anomalous behavior in every printer tested. For most printers it finds multiple vulnerabilities, 6 of which have been assigned CVE numbers, including buffer overflow and information disclosure.

Background The Asian population presents a high incidence of Fitzpatrick skin types III and IV. The management of skin tone is a very important cosmetic issue in these groups. Efficacy check of a new cosmetic concept to achieve skin color lightening arouses great interest. Objective To estimate the clinical efficacy of a new facial microfiber tissue (FMT) which combines a surface micropeeling technology (due to the structure of the microfibers) with skin whitening cosmetic actives in Asian skin. The FMT is a new concept featuring a dry microfiber tissue loaded with cosmetic actives, which is just wetted with little tap water before use. Methods A total of 34 females aged 21-58 years old with Fitzpatrick skin types III and IV were enrolled in this randomized, blank-controlled trial for 12 weeks. Participants applied FMT on the left or right forearm according to random assignment. At the same time, FMT was used on the face. Skin whitening effects on the forearm and face were evaluated using Mexameter MX18 and Minolta Spectrophotometer CM-2600d. In addition, assessment by subjects via a self-evaluation questionnaire was conducted at study end. Results The FMT treatment showed a significant whitening effect mainly on the forearm compared with blank control forearm. Facial whitening was also noted. No adverse reactions were reported during the study. Conclusion The new cosmetic concept of FMT can be used as an effective and safe whitening cosmetic agent.

BACKGROUND Skin imaging analysis, acting as a supplement to noninvasive bioengineering devices, has been widely used in medical cosmetology and cosmetic product evaluation. The main aim of this study is to assess the differences and correlations in measuring skin spots, wrinkles, vascular features, porphyrin, and pore between two commercially available image analysis software. MATERIALS AND METHODS Seventy healthy women were included in the study. Before taking pictures, the dermatologist evaluated subjects' skin conditions. Test sites included the forehead, cheek, and periorbital skin. A 2 × 2 cm cardboard was used to make a mark on the skin surface. Pictures were taken using VISIA® under three kinds light conditions and analyzed using VISIA® and IPP® respectively. RESULTS (1) Skin pore, red area, ultraviolet spot, brown spot, porphyrin, and wrinkle measured with VISIA® were correlated with those measured with IPP® (P

To explore efficacy of protein extracts from medium of Adipose-derived stem cells (ADSCs) via microneedles on Asian skin in a double-blind, split-face, randomized, control study.Thirty volunteers received the treatment, left-side and right-side of their face were randomly assigned to test side and control side. The protein extracts from medium of ADSCs were applied via microneedles into the test side and ultrapure water was applied into the control side. The only person who knew what was being used by each subject on each side of the face was the therapist. Clinical evaluation including instrument test and self-questionnaire was performed by independent observers before and after the treatment, which lasted for 3 months.All subjects completed the study. Compared to ultrapure water, the protein extracts from medium of ADSCs showed a statistically significant improvement for melanin index, skin brightness, gloss, skin roughness, elasticity, and wrinkles (p 0.05). More than 70% of the participants described that all wrinkles, firmness, elasticity, hydration, whitening, and radiance were strongly improved in the test side.Protein extracts from medium of ADSCs presented anti-aging and whitening efficacy via microneedles on Asian skin without skin adverse side.

This brief addresses the relative pose control for cooperative spacecraft during rendezvous and proximity operations with parametric uncertainties based on the noncertainty equivalence approach. The relative position dynamics modeled in the target’s line-of-sight coordinate frame and attitude synchronized dynamics described by modified Rodrigues parameters are formulated as the typical Euler–Lagrange form to facilitate six-degrees-of-freedom relative pose control design. Due to the immersion and invariance adaptive control approach, unknown parametric uncertainties are compensated online and the transient performance of closed-loop states can be regulated by both controller and estimator parameters. Asymptotic convergence of the relative position and relative attitude is proved rigorously in the Lyapunov framework. Numerical simulation of the nonlinear adaptive control scheme for spacecraft line-of-sight rendezvous and proximity operations is also presented to highlight potential closed-loop performance improvements compared with the application of classical certainty equivalence-based adaptive controllers.

In this article, we propose a novel state-based fault-localization approach. Given an observed failure that is reproducible under the same program input, this new approach uses two main techniques to reduce the state exploration cost. Firstly, the execution trace to be analyzed for the observed failure is successively narrowed by making the set of trace points in each step a cut of the dynamic dependence graph. Such a cut divides the remaining trace into two parts and, based on the sparse symbolic exploration outcome, one part is removed from further exploration. This process continues until reaching where the fault is determined to be. Second, the cut in each step is chosen such that the union of the program states from the members of the cut is of the minimum size among all candidate cuts. The set of statement instances in the chosen cut is called a minimum debugging frontier set (MDFS). To evaluate our approach, we apply it to 16 real bugs from real world programs and compare our fault reports with those generated by state-of-the-art approaches. Results show that the MDFS approach obtains high quality fault reports for these test cases with considerably higher efficiency than previous approaches.

A singularity-free nonlinear robust controller is proposed for miniature helicopters to accomplish trajectory tracking missions. The helicopter model is decomposed into a cascaded structure with some unmodeled dynamics. The controller development applies the hierarchical strategy. First, a position loop controller is designed based on a saturation control scheme using differential hyperbolic tangent functions, and criteria for choosing controller parameters are established to ensure the finite-time position tracking and to obviate singularity in the command attitude extraction. Singularity may also occur during the attitude tracking when the pitch of the helicopter reaches $\pm \frac{\pi }{2}$ . Based on a barrier Lyapunov function, an attitude loop controller is put forward with a backstepping technique, and an initial condition constraint for the nonsingular attitude tracking is deduced. Simulations illustrate the applicability of the proposed controller.

The pure electric vehicles and hybrid vehicles mostly use single battery pack for energy storage, which is easy to cause various battery problems. Moreover, short driving range and inconvenient charging are still the restrictive factors for the development and promotion of electric vehicles. A new kind of dynamic driving system was proposed in this paper -- Load isolated pure electric driving. According to the performance requirements of load isolated pure electric driving vehicle we made homologous parameter matching of the power system, and the driving system control strategy was carried on analysis based on the SOC of power batteries and the running conditions of vehicle.

Erectile dysfunction (ED) is a common comorbidity in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells (CCSMCs). Gene Expression Omnibus repository-based analysis identified the differentially expressed PDCD4 in DM rats. PDCD4 has also been determined as a putative gene under the regulatory control of microRNA-21-5p (miR-21-5p). This study aimed to further determine the functional role of miR-21-5p in CCSMCs in a rat model of diabetes mellitus-induced erectile dysfunction (DMED). CCSMCs were isolated from penile cavernous tissue and cultured in high glucose (HG) medium. The expression of miR-21-5p and/or PDCD4 was altered in CCSMCs, as directly or indirectly measured by CCK-8 assay, flow cytometry, and TUNEL assays. Furthermore, exosomes were isolated from mesenchymal stem cells (MSCs) transfected with miR-21-5p mimic or miR-21-5p inhibitor and co-cultured with CCSMCs. DMED rats were injected with lentivirus carrying PDCD4/siRNA-PDCD4 plasmids, or exosomes from MSCs containing miR-21-5p-agomir to explore their roles in vivo. The experimental data validated that PDCD4 was upregulated in cavernous tissue of DMED rats. miR-21-5p targeted and inhibited PDCD4. miR-21-5p was enriched in MSC-exosomes. Moreover, PDCD4 downregulation, miR-21-5p elevation or MSC-derived exosomal miR-21-5p reduced apoptosis and enhanced proliferation of CCSMCs cultured in HG medium. PDCD4 silencing or miR-21-5p-containing MSC-exosomes improved erectile function and smooth muscle density in DMED rats. Collectively, our findings suggested that MSC-derived exosomal miR-21-5p suppressed PDCD4 expression and ED in rats with DM.

In order to improve the deficiency of traditional vehicle mounted monitor and reduce the incidence of traffic accidents, a remote control multiple view monitor for the vehicle mounted mobile phone which is based on the technology of Internet of things is designed. The monitor includes the circuit board module, the camera module and the lift rod module. The monitor controls the operation of the multiple steering gears through the embedded circuit, and then controls the rotation of the lifting rod as well as the cloud deck which carries the camera; the router is used to generate the wireless signals which connect the mobile phone, and the mobile phone is used to send instructions and receive the collected signals. The monitor can realize the lifting and rotation of the camera through the remote control with the mobile phone, implementing acquisition of the scenes in multiple directions. With this monitor, it is possible to carry out the auxiliary observations while the vehicle is moving forward, backing up or perform the side parking or in the case that there is any high obstacle in front of the vehicle, and this will be helpful in avoid traffic accidents in an effective manner. This monitor can also be used for the household monitoring, the commercial monitoring as well as the monitoring in the public security system and the traffic system.

Chronic shoulder pain (CSP) is the third most common musculoskeletal problem. For maximum treatment effectiveness, most acupuncturists usually choose acupoint in the nonpainful side, to alleviate pain or improve shoulder function. This method is named opposite needling, which means acupuncture points on the right side are selected for diseases on the left side and vice versa. However, the underlying neural mechanisms related to treatment are currently unclear. The purpose of this study was to determine whether different mechanisms were observed with contralateral and ipsilateral acupuncture at Tiaokou (ST 38) in patients with unilateral CSP. Twenty-four patients were randomized to the contralateral acupuncture group (contra-group) and the ipsilateral acupuncture group (ipsi-group). The patients received one acupuncture treatment session at ST 38 on the nonpainful or painful sides, respectively. Before and after acupuncture treatment, they underwent functional magnetic resonance scanning. The treatment-related changes in degree centrality (DC) maps were compared between the two groups. We found alleviated pain and improved shoulder function in both groups, but better shoulder functional improvement was observed in the contra-group. Increased DC in the anterior/paracingulate cortex and decreased DC in bilateral postcentral gyri were found in the contra-group, while decreased DC in the bilateral cerebellum and right thalamus was observed in the ipsi-group. Furthermore, the DC value in the bilateral anterior/paracingulate cortex was positively correlated with the treatment-related change in the Constant–Murley score. The current study reveals different changes of DC patterns after acupuncture at contralateral or ipsilateral ST 38 in patients with CSP. Our findings support the hypothesis of acupoint specificity and provide the evidence for acupuncturists to select acupoints for CSP.

Purpose: Mapping the distribution of internal mammary sentinel lymph nodes (IM-SLNs) presented on single photon emission computed tomography in conjunction with computed tomography (SPECT/CT) images to explore the value of IM-SLN to guide tailored clinical target volume (CTV) delineation of postoperative prophylactic IMNI. Materials and methods: Ninety-seven patients who underwent preoperative lymphoscintigraphy by SPECT/CT and had imaging of IM-SLN were selected in this study. The imaging IM-SLNs on SPECT/CT of eligible patients were projected onto corresponding anatomical positions of a representative axial CT image. The IMN CTVs were delineated on the representative axial CT images according to the Radiation Therapy Oncology Group (RTOG) and Danish Breast Cancer Cooperative Group (DBCG) guideline, and defined as CTVRTOG and CTVDBCG. The location of the IM-SLNs was compared with the RTOG and DBCG guidelines of IMN target volume delineations, respectively. The intercostal space distribution of IM-SLNs was recorded. The distances from the CTVRTOG and CTVDBCG to the IM-SLNs were measured, respectively. Results: The total number of imaging IM-SLNs was 136. IM-SLNs were mostly found in the first intercostal space (40.4%), with 30.2, 24.3, 4.4, and 0.7% of IM-SLNs in the second, third, fourth, and fifth intercostal space, respectively. The average distance from the edge of the CTVRTOG and the edge of CTVDBCG to the central points of the IM-SLNs was 4.10 mm (SD, 3.3 mm) and 1.60 mm (SD, 2.6 mm), respectively (t = 16.640, P = 0.000). The average distance from the edge of CTVRTOG and the edge of CTVDBCG to the lateral border IM-SLN was 6.40 mm (SD, 3.5 mm) and 3.34 mm (SD, 3.3 mm), respectively (t = 19.815, P = 0.000). Only 18.4% of IM-SLN central points were included in the CTVRTOG, and 60.3% of IM-SLN central points were included in the CTVDBCG. When covering 90 and 100% of the IM-SLN center points, the CTVRTOG needs to expand 8 and 15 mm, respectively, and the CTVDBCG needs to expand 5 and 13 mm, respectively. Conclusion: Neither the RTOG nor DBCG consensus guideline about the delineation of IMN CTV was sufficient to cover 90% of IM-SLNs. For 90% coverage of IM-SLN central points, CTVRTOG needed to be expanded by 8 mm, and CTVDBCG needed to be expanded by 5 mm.

SOHO (small office/home office) routers provide services for end devices to connect to the Internet, playing an important role in the cyberspace. Unfortunately, security vulnerabilities pervasively exist in these routers, especially in the web server modules, greatly endangering end users. To discover these vulnerabilities, fuzzing web server modules of SOHO routers is the most popular solution. However, its effectiveness is limited, due to the lack of input specification, lack of routers' internal running states, and lack of testing environment recovery mechanisms. Moreover, fuzzing in general only reports memory corruption vulnerabilities, and fails to discover other vulnerabilities, e.g., web-based vulnerabilities. In this paper, we propose a solution SRFuzzer to address these issues. It is a fully automated fuzzing framework for testing physical SOHO devices. It continuously and effectively generates test cases by leveraging two input semantic models, i.e., KEY-VALUE data model and CONF-READ communication model, and automatically recovers testing environment with power management. It also coordinates diversified mutation rules with multiple monitoring mechanisms to trigger multi-type vulnerabilities. To the best of our knowledge, it is the first whole-process fully automated fuzzing framework for SOHO routers. We ran SRFuzzer on 10 popular routers across five vendors. In total, it discovered 208 unique exceptional behaviors, 97 of which have been confirmed as 0-day vulnerabilities. The experimental results show that SRFuzzer outperforms state-of-the-art solutions in terms of types and number of vulnerabilities found.

COTS software products are developed extensively on top of OSS projects, resulting in OSS reuse vulnerabilities. To detect such vulnerabilities, finding OSS reuses in COTS software has become imperative. While scalable to tens of thousands of OSS projects, existing binary-to-source matching approaches are severely imprecise in analyzing COTS software products, since they support only a limited number of code features, compute matching scores only approximately in measuring OSS reuses, and neglect the code structures in OSS projects.We introduce a novel binary-to-source matching approach, called B2SFinder1, to address these limitations. First of all, B2SFinder can reason about seven kinds of code features that are traceable in both binary and source code. In order to compute matching scores precisely, B2SFinder employs a weighted feature matching algorithm that combines three matching methods (for dealing with different code features) with two importance-weighting methods (for computing the weight of an instance of a code feature in a given COTS software application based on its specificity and occurrence frequency). Finally, B2SFinder identifies different types of code reuses based on matching scores and code structures of OSS projects. We have implemented B2SFinder using an optimized data structure. We have evaluated B2SFinder using 21991 binaries from 1000 popular COTS software products and 2189 candidate OSS projects. Our experimental results show that B2SFinder is not only precise but also scalable. Compared with the state of the art, B2SFinder has successfully found up to 2.15x as many reuse cases in 53.85 seconds per binary file on average. We also discuss how B2SFinder can be leveraged in detecting OSS reuse vulnerabilities in practice.

IntroductionSubjective cognitive decline (SCD) refers to individuals’ perceived decline in memory and/or other cognitive abilities relative to their previous level of performance, while objective neuropsychological deficits are not observed. SCD may represent a preclinical phase of Alzheimer’s disease. At this very early stage of decline, intervention could slow the rate of incipient decline to prolong and preserve cognitive and functional abilities. However, there is no effective treatment recommended for individuals with SCD. Acupuncture, as a non-pharmacological intervention, has been widely employed for patients with cognitive disorders.Methods and analysisThe proposed study is a randomised, assessor-blinded and placebo-controlled study that investigates the efficacy and mechanism of acupuncture in SCD. Sixty patients with SCD will be randomly allocated either into an acupuncture group or a sham acupuncture group. They will receive 24 sessions of real acupuncture treatment or identical treatment sessions using a placebo needle. Global cognitive changes based on a multidomain neuropsychological test battery will be evaluated to detect the clinical efficacy of acupuncture treatment at baseline and end of treatment. MRI scans will be used to explore acupuncture-related neuroplasticity changes. Correlation analyses will be performed to investigate the relationships between the changes in brain function and symptom improvement.Ethics and disseminationThe trial was approved by the research ethics committee. The results of the study will be published in a peer-reviewed academic journal and will also be disseminated electronically through conference presentations.Trial registration numberNCT03444896.

When evaluating Static Application Security Testing (SAST) tools, benchmarks based on real-world softwares are considered more representative than synthetic micro benchmarks. Generated from real-world software, the test cases in such kind of benchmarks usually contain multiple syntactic features which affect the vulnerability detection results reflecting SAST tools' capabilities in real-world settings. However, most existing benchmarks based on real-world software pay little attention to these syntactic features so that only limited information about the capabilities of SAST tools can be obtained from the evaluation results. In this paper, we provide a method of constructing benchmarks and evaluating SAST tools, which leverages the syntactic features to support the evaluation to be more explainable. To demonstrate the effectiveness, we applied our method to the benchmark built by Misha Zitser et al., generated 10 groups of test cases, and evaluated 2 SAST tools with them. The result shows that, with the benchmark constructed by our method, the evaluation could be more explainable which helps us to gain more information about the SAST tools' capabilities of vulnerability detection.

Ya-Nan Zhang,1 Jian-Wei Huo,1 Yi-Ran Huang,2 Ying Hao,3 Zi-Yue Chen41Department of Radiology, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, People’s Republic of China; 2School of Acupuncture-Moxibustion & Tuina, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Beijing International Center for Mathematical Research, Peking University, Beijing 100871, People’s Republic of China; 4Department of Acupuncture and Moxibustion, Yanshan Hospital, Beijing 102500, People’s Republic of ChinaPurpose: The current study aimed to explore the central mechanism of primary dysmenorrhea (PD) by investigating the alterations in resting state amplitude of low-frequency fluctuation (ALFF) and regional cerebral blood flow (CBF) between PD patients and healthy controls (HCs).Patients and methods: A total of 34 female subjects including 20 PD patients and 14 HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling technique (ASL) MRI during menstrual phase. Subsequently, the differences in ALFF and CBF were compared in the two groups. The visual analog scores for pain (VAS-P) and for anxiety (VAS-A) were applied to assess cramping pain and related symptoms in PD patients. Finally, Pearson’s correlation analysis was performed to analyze relationships between the neuroimaging findings and clinical characteristics.Results: Compared to HCs, PD patients had decreased ALFF in the right cerebellum posterior lobe, right middle temporal gyrus, right parahippocampal gyrus, right hippocampus, right brainstem and left parietal lobe. In addition, elevated CBF values were observed in the right inferior frontal gyrus, right precentral gyrus, and right superior temporal gyrus. There was no significant correlation between ALFF, CBF values and clinical characteristics including onset age of dysmenorrhea, VAS-A, and VAS-P in PD patients.Conclusion: The preliminary alterations of ALFF and CBF values in PD patients were observed in different pain-related brain regions, which were involved in multiple dimensions of pain and pain modulation. The combination of rs-fMRI and ASL MRI might provide complementary information for a better understanding of the central mechanism in PD.Keywords: primary dysmenorrhea, resting state functional magnetic resonance imaging, amplitude of low frequency fluctuation, arterial spin labeling, cerebral blood flow

A robust nonlinear control strategy is presented for a cooperative spacecraft rendezvous and docking maneuver, where the pursuer spacecraft is subject to input saturation and actuator faults. The nonlinear coupled models for relative attitude and relative position dynamics are expressed in the pursuer body-fixed frame. A novel control strategy based on feedback linearization framework is developed, and a second-order disturbance observer is employed to estimate and compensate all uncertainties including parametric uncertainties, external disturbances, input saturation and actuator faults. It is proved that the closed-loop systems are uniformly ultimately bounded by using Lyapunov theory. Numerical simulations are given to illustrate effectiveness of the proposed control strategy.

This paper presents a six-degree-of-freedom relative motion control method for autonomous spacecraft rendezvous and proximity operations subject to input saturation, full-state constraint, kinematic coupling, parametric uncertainty, and matched and mismatched disturbances. Relative rotational and relative translational controllers are developed separately based on a unified adaptive backstepping technique. Both element-wise and norm-wise adaptive estimation techniques are used for handling parametric uncertainties, kinematic couplings, and matched and mismatched disturbances, where the bounds of disturbances are unknown. Two auxiliary design systems are employed to deal with input saturation in the relative rotational and relative translational control designs, and the stability of the saturated control solution is verified. Full-state constraint of the relative pose motion is handled by using barrier Lyapunov functions while achieving a satisfactory control performance. All signals in the closed-loop system are guaranteed to be uniformly ultimately bounded, and the relative motion states are all restricted within the known constraints. Compared with the previous control designs of spacecraft rendezvous and proximity operations, the proposed control strategy in this paper can simultaneously deal with input saturation, full-state constraint, kinematic coupling, parametric uncertainty, and matched and mismatched disturbances. Experimental simulation results validate the performance and robustness improvement of the proposed control strategy.

The pure electric vehicles and hybrid vehicles mostly use single energy storage battery pack, which easily cause various battery problems. Moreover, short driving range and inconvenient charging are still the key problems to be solved. A new kind of dynamic driving system aiming at these problems was put forward in this paper--Load isolated pure electric driving. This paper made homologous parameter matching of power system and established full vehicle dynamic model of Load isolated pure electric driving vehicle by MATLAB/SIMULINK, the feasibility and advantage of the Load isolated pure electric driving system was verified through performance simulation.

The six-degrees-of-freedom relative motion control of a chaser spacecraft approaching a free tumbling target in deep space is investigated in this paper. In view of unknown model uncertainties and complex dynamic couplings in the dynamical model, a direct adaptive fuzzy nonlinear controller is constructed by using fuzzy logic systems to approximate the uncertainties and couplings, where the parameter vectors of fuzzy systems are estimated online by using a projection-based adaptive control method. Due to the great dimension of the system variables, hierarchical fuzzy logic systems are employed in the fuzzy control to reduce the amount of fuzzy rules and alleviate the online computation burden in the proposed control algorithm. It is proved that tracking errors of the chaser spacecraft and adaptive parameters of the fuzzy systems are uniformly ultimately bounded. Numerical simulations are performed to demonstrate the performance of the proposed control strategy.

The control problem of autonomous proximity phase during rendezvous and docking is studied for a chaser spacecraft subject to parametric uncertainty and unknown external disturbance approaching to a tumbling non-cooperative space target. A coupled relative motion model is established for the autonomous spacecraft proximity missions based on the relative motion information and chaser’s motion information. Based on the cascaded structure of the six degrees-of-freedom coupled model, the backstepping technology combined with element-wise and norm-wise adaptive control methods is used to design a relative position controller firstly, then the same method is also applied to the design of the relative attitude controller. Asymptotic stability is proven uniformly for the six degrees-of-freedom closed-loop system, and the performance of the controlled overall system is demonstrated via a representative numerical example.

In the process of assisted driving, accurately understanding the linguistic information transmitted by surrounding vehicles is the prerequisite for making correct driving decisions. In this paper, the neural network was partly used for vehicle detection. The recognition of the front vehicle taillights is based on the taillight recognition mechanism and image processing technology. The taillights are then positioned by using their colour and shape characteristics. The red-green-blue (RGB) and cyan-magenta-yellow (CMY) colour spaces were used to establish a taillight recognition mechanism to detect the taillight status of the front car, so as to understand the driving intention of the front car. The experimental results show that the method can accurately identify the state of the front taillights during the day.

Introduction Mild local hyperthermia at 44°C has been proven efficacious in the treatment of cutaneous warts induced by human papillomavirus (HPV), while its effect on cervical intraepithelial neoplasia (CIN) caused by high risk type of HPVs has not been reported. Patient concerns Three patients with low grade CIN and positive high risk HPV types (HPV 16, 31, 52, 56, 58) are reported in this study. Diagnosis The diagnosis was based on identification of HPV types and abnormal cytological findings. Interventions The 3 patients were treated with local hyperthermia from ceramic heating (surface temperature, 44°C) to cervix. The treatment was delivered once a day for 3 consecutive days, plus two similar treatments 10 ± 3 days later, with each session lasting 30 minutes. HPV and cytology test were performed 3 months thereafter. Outcomes All the 3 patients recovered to normal cytological findings. Two of the patients were negative for HPV, the remaining patient with pre-treatment HPV 56 and 58 positivity changed to HPV58 positive alone. Conclusion This pilot observation inspires that mild local hyperthermia be recommended as a new method in the treatment of CIN patients with persistent HPV infection, once validated by qualified RCT.

Open-source licenses are widely used in open-source projects. However, developers using or modifying the source code of open-source projects do not always strictly follow the licenses. GPL and AGPL, two of the most popular copyleft licenses, are most likely to be violated, because they require developers to open-source the entire project if any code under GPL/AGPL protection is included whether modified or not. There are few license violation detectors focusing on binary software, owning to the challenge of mapping binary code to source code efficiently and accurately at large scale. In this paper, we propose a scalable and fully-automated system to check open-source license violation of binary software at large scale. We match source code to binary code by analyzing file attributes of executable files and code features that are not affected by compilation and could vary between projects. Moreover, to break the barrier of large-scale analysis, we introduce an automatic extractor to parse executable files from installation packages that are broadly available in software download sites. In empirical experiments of binary-to-source mapping, we have got a remarkable high accuracy of 99.5% and recall of 95.6% without significant loss of precision. Besides, 2270 pairs of binary-to-source mapping relationships are discovered, with 110 license violations of GPL and AGPL licenses related to 7.2% of the 1000 real-world binary software projects.

Objective. A retrospective analysis of clinical characteristics and immunological manifestations of primary Sjogren’s syndrome (pSS) patients with or without renal involvement was conducted in order to elucidate the potential risk factors of renal damage in pSS and evaluate the condition. Methods. A total of 1002 patients, who fulfilled the 2002 classification criteria for pSS from the Second Affiliated Hospital of Shanxi Medical University, were enrolled in the cross-sectional study. Clinical, immunological, and histological characteristics were compared between pSS patients with and without renal involvement, and potential risk factors of renal involvements in pSS patients were examined by multivariate analysis. Results. Among these pSS patients, there were 162 cases (16.17%) with and 840 cases (83.83%) without renal damage. Serious edema of both lower limbs, interstitial nephritis, and renal tubular acidosis were found in the pSS with renal damage group. Compared with simple pSS patients, the levels of creatinine, cystatin C, and alpha-1-microglobulin (α1-MG) in the pSS with renal damage group were significantly increased. The difference between the two groups was statistically significant (P<0.05). The AUC of the combination of creatinine and α1-MG and creatinine, α1-MG, and creatinine was statistically larger than that of creatinine, and the biomarker of the biggest AUC is the combination of creatinine and α1-MG. Conclusion. The main clinical manifestations of pSS with renal damage were edema of the lower limbs, interstitial nephritis, and renal tubular acidosis. Creatinine and α1-MG are effective indicators for renal function in pSS, which may provide a better understanding for clinical decision-making.

Web-based applications delivered using clouds are becoming increasingly popular due to less demand of client-side resources and easier maintenance than desktop counterparts. At the same time, larger attack surfaces and developers’ lack of security proficiency or awareness leave Web applications particularly vulnerable to security attacks. On the other hand, diversity has long been considered as a viable approach to detecting security attacks since functionally similar but internally different variants of an application will likely respond to the same attack in different ways. However, most diversity-by-design approaches have met difficulties in practice due to the prohibitive cost in terms of both development and maintenance. In this work, we propose to employ opportunistic diversity inherent to Web applications and their database backends to detect injection attacks. We first conduct a case study of common vulnerabilities to confirm the potential of opportunistic diversity for detecting potential attacks. We then devise a multi-stage approach to examine features extracted from the database queries, their effect on the database, the query results, as well as the user-end results. Next, we combine the partial results obtained from different stages using a learning-based approach to further improve the detection accuracy. Finally, we evaluate our approach using a real world Web application.

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have uncovered the disruptions of functional brain networks in primary insomnia (PI) patients. However, the etiology and pathogenesis underlying this disorder remains ambiguous, and the insomnia related symptoms are influenced by a complex network organization in the brain. The purpose of this study was to explore the abnormal intrinsic functional hubs in PI patients using a voxel-wise degree centrality (DC) analysis and seed-based functional connectivity (FC) approach. Methods: A total of 26 PI patients and 28 healthy controls were enrolled, and they underwent resting-state fMRI. Degree centrality was measured across the whole brain, and group differences in DC were compared. The peak points, which significantly altered DC between the two groups, were defined as the seed regions and were further used to calculate FC of the whole brain. Later, correlation analyses were performed between the changes in brain function and clinical features. Results: Primary insomnia patients showed DC values lower than healthy controls in the left inferior frontal gyrus (IFG) and middle temporal gyrus (MTG) and showed a higher DC value in the right precuneus. The seed-based analyses demonstrated decreased FC between the left MTG and the left posterior cingulate cortex (PCC), and decreased FC was observed between the right precuneus and the right lateral occipital cortex. Reduced DC in the left IFG and decreased FC in the left PCC were positively correlated with the Pittsburgh sleep quality index and the insomnia severity index. Conclusions: This study revealed that PI patients exhibited abnormal intrinsic functional hubs in the left IFG, MTG, and the right precuneus, as well as abnormal seed-based FC in these hubs. These results contribute to better understanding of how brain function influences the symptoms of PI.

Internet of Things(IOT) technology provides sufficient information technology and necessary decision-making basis for intelligent transportation. Internet of vehicles(IOV) is based on the architecture of the perception layer, network layer, and application layer. This article focuses on the tail light status in the perception layer of automotive active safety systems and proposes a method of vehicle taillamp detection and recognition based on active contour extraction and color feature analysis to solve the problem of information perception against the front vehicle. First, the front vehicles are detected and extracted by convolutional neural network and active contour models. Second, it analyzes the characteristics of taillamp pair and then segment the correct taillamp pair by color space conversion and location correlation principle. On this basis, the histograms distribution of taillamp are analyzed in different states and complete the recognition of taillamp. The experimental results show that the method can accurately identify the taillamp signal of the front vehicle in the daytime and effectively reduce the rate of false judgement caused by light interference.

Background: Ischemic cerebral infarction is a severe clinical condition that can cause serious mortality. Artesunate, an anti-malarial drug that is widely used in cancer treatment, is known to facilitate accelerated cell apoptosis. The aim of this study is to explore the possible neuroprotective effects of artesunate on hypoxic-ischemic cells in rats. Methods: Middle cerebral artery occlusion (MCAO) rats were treated with artesunate in different doses to observe their survival rate. Primary hippocampal neurons were deprived of oxygen-glucose to induce ischemia symptoms. Western blot was performed to determine the protein expressions of p-mTOR, Beclin-1, and Mcl-1. A five-point scale was used to detect neurological deficit. Cell apoptosis was measured using a TUNEL assay. Results: Artesunate supplementation protected MCAO rats from death and ameliorated brain injury among them. Artesunate administration decreased the expression of p-mTOR, increased the expressions of Beclin-1 and Mcl-1, and decreased the activity of caspase-3 in both the rats' ischemia cerebral cortices and their primary ischemia hippocampal neurons when compared with artesunate-absent ischemic brains and cells. The neuroprotective effects of artesunate were abolished by either leucine (LEU) or 3-MA, while the effects of rapamycin were reversed by 3-MA. In vivo experiments verified the protective effects of artesunate on brain-infarct rats. Conclusion: The results indicate the protectiveness of artesunate against ischemic cerebral infarction, whereas the protectiveness might increase autophagy through regulating the activity of mTOR.

This paper investigates relative motion control for a rigid spacecraft with parametric uncertainties and external disturbances to approach an unknown tumbling space target. State feedback controllers for relative translation and relative rotation are designed based on a unified adaptive robust control with L2-gain performance. Parametric uncertainties and unknown dynamic couplings are compensated online with adaptive update laws. An external disturbance is treated as a bounded perturbation input for the system. To synthesize the controllers and achieve a prescribed L2-gain performance index, the feedback gains of the controllers are designed by solving linear matrix inequalities. Indeed, perturbation attenuation with respect to the controlled output is ensured in the L2-gain sense. Moreover, in the absence of perturbation input in the closed-loop system, asymptotical convergence of the relative position and relative attitude are proved by using the Lyapunov stability theory. Numerical simulations are perf...

This paper investigates a robust adaptive backstepping neural networks control for spacecraft rendezvous and docking with the coupled position and attitude dynamics. Backstepping technique is applied as the main control structure. The uncertainties of the relative dynamics are compensated by using radial basis function neural networks (RBFNNs). An adaptive switching controller is designed by combining a conventional adaptive neural networks controller and an extra robust controller. The conventional RBFNNs dominate in the neural active region, while the robust controller retrieves the transient outside the active region. The controllers work together not only improving the control accuracy, but also reducing real-time computing burden of the controller. Lyapunov theory is employed to prove that the states are globally uniformly ultimately bounded. Simulation example is given to illustrate the effectiveness of the proposed control strategy.