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Abstract Robust optimization is an essential tool for addressing the uncertainties in power systems. Most existing algorithms, such as Benders decomposition and column‐and‐constraint generation (C&CG), focus on robust optimization with decision‐independent uncertainty (DIU). However, increasingly common decision‐dependent uncertainties (DDUs) in power systems are frequently overlooked. When DDUs are considered, traditional algorithms for robust optimization with DIUs become inapplicable. This is because the previously selected worst‐case scenarios may fall outside the uncertainty set when the first‐stage decision changes, causing traditional algorithms to fail to converge. This study provides a general solution algorithm for robust optimization with DDU, which is called dual C&CG. Its convergence and optimality are proven theoretically. To demonstrate the effectiveness of the dual C&CG algorithm, we used the do‐not‐exceed limit (DNEL) problem as an example. The results show that the proposed algorithm can not only solve the simple DNEL model studied in the literature but also provide a more practical DNEL model considering the correlations among renewable generators.

During checking continuous waveform record, it was found that some stations of Tianjin such as EWZ were significantly affected by one unknown noise, and EWZ station was the most seriously affected. Long term observations had also found that this noise cannot be observed for uncertainly several days each year. This noise was all year round and did not change with day and night time, and it had been existed for many years. This noise was different from typical environmental background noise and had some fixed characteristics. This article studied the noise from several aspects such as its own characteristic, its coverage of influence, spectral characteristics, and impact on earthquake records. The research has shown that the noise was not affected by natural factors such as weather and season, and had a characteristic of amplitude decreasing as the distance increasing from EWZ station. The main frequency of this noise ranged 1～2 Hz. The impact of noise was relatively wide and it can be recorded by 12 surrounding stations, with YGZ station being the farthest and approximately 58 km away from EWZ station. Through polarization analysis, it was found that the propagation of noise had a specific directionality, so it is preliminary judged that this noise had the characteristic of fixed source noise. This noise will have an impact on seismic records, reducing the seismic phase pickup rate, and even completely submerging it in the noise. Frequency filtering can improve it.

Background & Aims: Hepatic recompensation may be achieved in patients with decompensated cirrhosis due to chronic hepatitis B (CHB) upon effective suppression of viral replication by nucleos(t)ide analogues (NAs). However, the optimal timing and predictors of recompensation and the subsequent clinical course of patients with CHB with vs. without recompensation are not well-defined. Methods: This study was a retrospective extension of a multi-centre prospective cohort, focusing on patients with CHB and decompensated cirrhosis treated with entecavir. We followed patients beyond treatment week 120 until a second decompensation event or June 2023. We identified the optimal timing and predictors of recompensation by week 120, evaluated durability of recompensation in patients fulfilling recompensation criteria by week 120 and examined late recompensation in those who did not fulfil it by week 120. Results: At treatment week 24, serum albumin ≥34 g/L predicted recompensation by week 120. The Brec-PAS model offered good predictive ability for recompensation by week 120. Of the 283 patients who finished 120 weeks of therapy, 175 were followed beyond week 120 (median follow-up: 240 weeks). Among the 106 patients achieving recompensation by week 120, 92 (86.8%) maintained recompensation for another 120 (72-168) weeks. Among the 69 patients without recompensation by week 120, 40.6% attained late recompensation during the subsequent 120 (72-168) weeks. Additionally, hepatocellular carcinoma incidence was lower in the recompensated group (5.0% vs. 16.13%, p = 0.002). Conclusions: A serum albumin ≥34 g/L at treatment week 24 predicted recompensation by week 120. Recompensation achieved by week 120 of NA treatment is maintained in >80% of patients in the long term. Some patients may achieve recompensation only after >120 weeks of NA treatment. The incidence of hepatocellular carcinoma was reduced but not completely abolished after recompensation. Impact and implications: Our research provides a meaningful contribution to understanding the long-term prognosis of recompensation in patients with chronic hepatitis B and decompensated cirrhosis, as well as to evaluating the predictive value of serum albumin levels, offering a comprehensive view of clinical outcomes after recompensation. The significance of early biomarkers in guiding therapeutic decisions is highlighted, shedding light on the continued benefits and possible risks after recompensation. This enhances the capability for more precise prognostic evaluations and informed therapeutic strategies. For healthcare providers, these insights afford a detailed perspective on patient monitoring and intervention planning, underscoring the need for ongoing assessment past the initial recompensation phase.

Abstract The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction

AbstractContext Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS.Objective This study determines whether baicalin could affect the progression of PCOS.Materials and methods To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 μM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 μM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect.Conclusions Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

Abstract. To facilitate the achieving of the goal of “eliminating viral hepatitis as a major public health threat by 2030” set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large-scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B–related disease burden.

Abstract Background Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation. Methods This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred. Results Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P

Existing manual detection methods have limitations, particularly for pavement cracks in complex backgrounds, which are manifested in low recognition accuracy, high misjudgment rate, and long time-consuming. To overcome these problems, artificial intelligence technology and charge-coupled devices (CCD) imaging technology are combined to construct an automatic identification method for pavement hidden cracks under complex background interference conditions. First, the classic semantic segmentation model U-net is selected as the basic model, and the MobileNet lightweight network is utilized to replace the encoder part of U-Net with huge parameters, to realize the lightweight of the model and improve the segmentation effect of pavement cracks. On this basis, the Atrous Channel Pyramid Attention (ACPA) mechanism is introduced into the U-net to further improve contextual information capability to focus on selectively relevant features. A pavement crack data set containing different complex and diverse crack types and background noise is used to evaluate the effectiveness and scope of application of the developed model. Quantitative evaluation results show that the developed model achieves an overall performance in the test set with a precision of 88.84%, recall of 89.76%, accuracy of 98.87%, and IoU of 89.95%, respectively. Combined with the analysis of the results of the comparison experiment and the ablation experiment, it can be inferred that the utilization of the MobileNet lightweight network to replace the encoder part of U-net can effectively construct a lightweight model while the ACPA module can effectively perform multi-scale and long-distance cross-channel interaction, help suppress useless features, strengthen useful features, and help the network learn stronger feature representations of hidden areas of pavement cracks.

Increasing penetration of renewable energy generation poses a challenge to power system inertia adequacy. It is vital to provide long-term incentive signals to induce a generation mix with adequate inertia supply. However, existing literature rarely studies inertia incentive mechanisms or considers inertia constraints when making generation investment decisions. Thus, we propose an inertia market to quantify the value of inertia and to remunerate inertia provision. To examine the impacts of the inertia market on generation mix, we then propose a stochastic bilevel generation investment equilibrium model that depicts a multi-leader and multi-follower Stackelberg game. The lower level of the model considers the proposed inertia market, along with the energy, reserve, and capacity markets. The upper level considers multiple profit-maximizing strategic producers, and each producer is able to build gas-fired generators, wind generators, and energy storages. Numerical experiments demonstrate that a generation mix with adequate inertia supply can be induced with the proposed inertia market whereas there can be inertia shortage without the inertia market. Interestingly, considering carbon taxes, it is more cost-competitive to invest in wind resources with virtual inertia facilities than to substitute wind resources by thermal generators. Correspondingly, the introduction of an inertia market does not significantly reduce wind generation shares but boosts virtual inertia facility penetration. Our findings imply a future power system powered by fully decarbonized power resources with adequate inertia.

The National Electricity Market (NEM) in Australia was suspended during June 15-23, 2022, with a primary attribution to the lack of available generation capacity. This incident is noteworthy because it was the first market suspension in NEM's history and took place in a major energy exporting country. In this letter, we review the outline and impacts of the incident. From the perspectives of market regulation, electricity supply, and electricity demand, we identify three underlying causes of the market suspension and offer four recommendations for the market mechanism evolution to ensure power supply security.

Abstract The development of distributed energy resources, such as rooftop photovoltaic (PV) panels, batteries, and electric vehicles (EVs), has decentralized the power system operation, where transactive energy markets empower local energy exchanges. Transactive energy contributes to building a low‐carbon energy system by better matching the distributed renewable sources and demand. Effective market mechanisms are a key part of transactive energy market design. Despite fruitful research on related topics, some practical challenges must be addressed. This review surveys three practical issues related to information exchange in transactive energy markets: asynchronous computing, truthful reporting, and privacy preservation. The state‐of‐the‐art results are summarized and relevant multidisciplinary theories are introduced. Based on these findings, several potential research directions are suggested that could provide insights for future studies.

Transmission network expansion can significantly improve the penetration level of renewable generation. However, existing studies have not explicitly revealed and quantified the trade-off between the investment cost and penetration level of renewable generation. This paper proposes a distributionally robust optimization model to minimize the cost of transmission network expansion under uncertainty and maximize the penetration level of renewable generation. The proposed model includes distributionally robust joint chance constraints, which maximize the minimum expectation of the renewable utilization probability among a set of certain probability distributions within an ambiguity set. The proposed formulation yields a two-stage robust optimization model with variable bounds of the uncertain sets, which is hard to solve. By applying the affine decision rule, second-order conic reformulation, and duality, we reformulate it into a single-stage standard robust optimization model and solve it efficiently via commercial solvers. Case studies are carried on the Garver 6-bus and IEEE 118-bus systems to illustrate the validity of the proposed method.

Chronic liver disease (CLD) is a leading health problem impacting the quality of life globally. China shares a major global burden of CLD—including alcoholic liver disease, nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease, and drug-induced liver injury, except for chronic viral hepatitis. Several exogenous toxins or endogenous metabolic insults trigger hepatic pathology toward steatosis, inflammation, and fibrosis, which, if left untreated, may culminate in liver cirrhosis. Oxidative stress is a common pathomechanism underlying all phenotypes of toxic liver injury; thus, these may be brought under a unified entity, viz. toxic liver disease (TLD). Therefore, a common strategy to treat TLD is to use antioxidants as hepatoprotective agents. The cornerstone for treating fatty liver disease is lifestyle modification, diet, exercise, and behavioral therapy, along with the limited use of pharmacological agents. Available preclinical and clinical evidence indicates that silymarin is a hepatoprotective agent with established antioxidant, anti-inflammatory, antifibrotic effects. An international expert panel of clinicians was convened to discuss combining alcoholic liver disease, nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease, drug-induced liver injury, and liver cirrhosis under the single definition of TLD, based on the shared pathologic mechanism of oxidative stress. The panel highlighted the significance of silymarin as an antioxidant treatment for TLD.

Abstract Phasor measurement units (PMUs) have been widely deployed in power grids, while the bad PMU data problem threatens power system monitoring and control. This paper first gives the objective of the bad PMU data detection and gives an illustrative bad data instance. Then, the time‐series PMU data of neighbouring buses are cast as a two‐dimensional diagram, of which the spatio‐temporal correlation analysis is performed to design the normal and outlier data detection problem. Three clustering methods, including linear regression, density‐based spatial clustering of applications with noise (DBSCAN), and Gaussian mixture models (GMM) are ensembled for bad PMU data detection. Moreover, the statistical analysis and bound modification of data clustering are developed to further improve the detection accuracy. Finally, the procedure of the two‐stage bad PMU data detection is given, which consists of ensemble learning and modification. The proposed hybrid clustering‐based bad data detection is unsupervised and is applied to online bad PMU data detection with a short computation time. Visible and numerical case study results validate the outperformance of the proposed method.

ObjectiveThe role of stereotactic body radiation therapy (SBRT) for treating small hepatocellular carcinoma (sHCC) has gained increasing recognition. However, the prognosis and risk factors for recurrence in patients with sHCC remain unclear. This study investigated the risk factors for the recurrence of hepatitis B virus (HBV)-related sHCC after SBRT.MethodsA total of 240 HBV-related sHCC patients treated with SBRT between March 2011 and March 2020 were retrospectively analyzed. The cumulative probability of recurrence was calculated according to the Kaplan–Meier method. Univariate and multivariate analyses were performed with Cox proportional hazard models.ResultsRecurrent hepatocellular carcinoma developed in 134 (55.8%) patients at a median time of 27 months after SBRT. The one- and two-year rates of recurrence were 20.9 and 45.0%, respectively. The median follow-up time was 30 months. The Cox multivariate analysis indicated that age (P = 0.029, HR [1.019, 1.002–1.037]), tumor size (P = 0.012, HR [1.227, 1.045–1.440]), and aspartate aminotransferase-to-platelet ratio index (APRI) (P = 0.005, HR [1.911, 1.221–2.989]) were independent risk factors for recurrence.ConclusionPatients receiving SBRT for HBV-related sHCC may be at greater risk of recurrence if they have a high APRI score combined with advanced age and large tumor size.

BackgroundPolyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury.MethodsThis study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated.ResultsThe final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: −3.7, 95% CI, −6.0 to −1.5 U/L/day; −2.4, 95% CI, −4.5 to −0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (−5.2, 95% CI, −5.8 to −4.5 U/L/day; −3.5, 95% CI, −4.2 to −2.7 U/L/day; −4.9, 95% CI, −6.2 to −3.7 U/L/day, −0.07, 95% CI, −0.09 to −0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (−2.6, 95% CI, −3.3 to −1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (−1.4, 95% CI, −2.4 to −0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC.ConclusionThis was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

The P/S-style spectral ratio method is used to process and analyze the records of several stations with high SNR in Xiangshui explosion. An earthquake that occurred about 7 kilometers away from it on January 19，2013 was selected as the comparison event. In the frequency range of 2—15 Hz，for more than 90% stations，the P/S amplitude spectrum ratio of explosion is greater than 1，and the value of natural earthquake is less than 1，while it reaches 100% in the range of 4—15 Hz. In order to further verify the feasibility of this method in judging explosions and earthquakes，this paper calculated the Tianjin Port explosion on August 12，2015，and obtained the same results. This study provides a case study for using P/S-style spectral ratio method to verify low magnitude explosion. At the same time，this paper analyzes the waveform characteristics and spectrum characteristics of the Xiangshui explosion. We concluded that the seismic phase of this event is relatively single，which is similar to an ordinary blasting record，and there is no low-speed air-pressure and ground coupled Rayleigh wave as in the Tianjin Port explosion. And the event has two main frequencies，which are between 0.2—1 Hz and 4—10 Hz respectively.

Objectives: To investigate the factors and virological significance of serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after long-term antiviral therapy with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). Methods: In total, 51 treatment-naïve patients with CHB were included in the study. Clinical data were collected at baseline, during 5 years and at year 10 of NA treatment. Serum HBV pgRNA status of 51 patients was determined at year 5. Results: At year 5, 45% of the patients remained positive for HBV pgRNA. There were significant differences in baseline hepatitis B e antigen (HBeAg) status, HBV DNA load and hepatitis B surface antigen (HBsAg) levels between patients testing positive and negative for HBV pgRNA at year 5. Serum HBV pgRNA status and serum HBV DNA load were correlated after 5 years of NA treatment (r = 0.347, P = 0.013). Being HBV pgRNA positive at year 5 was an independent risk factor for sustainedly undetectable HBV DNA after 10 years of NA treatment (odds ratio 13.638, 95% confidence interval 1.32–140.81; P = 0.028). Furthermore, HBV pgRNA status at year 5 was associated with HBV DNA re-appearance at year 10 (P = 0.009). Conclusions: HBV pgRNA status at year 5 can reveal HBV covalently closed circular DNA (cccDNA) activity, and HBV pgRNA positivity after long-term antiviral therapy may indicate higher transcriptional activity of HBV cccDNA. Long-term dynamic monitoring of HBV pgRNA should be considered.

Abstract Background Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Methods Collected samples from different outcomes of HBV infection and performed genotyping by Affymetrix 500 k SNP Array. GCTA tool, PLINK, and Bonferroni method were applied for analysis of genotyping and disease progression. ANOVA was used to evaluate the significance of the association between biomarkers and genotypes in healthy controls. PoMo, FST, Vcftools and Rehh package were used for building the racial tree and population analysis. FST statistics accesses 0.15 was used as a threshold to detect the signature of selection. Results There are 1031 participants passed quality control from 1104 participants, including 275 HBV clearance, 92 asymptomatic persistence infection (ASPI), 93 chronic hepatitis B (CHB), 188 HBV-related decompensated cirrhosis (DC), 214 HBV-related hepatocellular carcinoma (HCC) and 169 healthy controls (HC). In the case–control study, one novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57 × 10−6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62 × 10−6; SNP: rs4661093, Gene: ETV3, P = 2.26 × 10−6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85 × 10−6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Underlying the evolutionary study of HBV-related genes in public database, the derived allele of two HBV clearance related loci, rs3077 and rs9277542, are under strong selection in European population. Conclusions In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

We aim to investigate the impact of different clinical phases’ definitions of chronic hepatitis B (CHB) infection on the profiles of grey zone, based on HBV guidelines set by the Chinese Society of Hepatology and Chinese Society of Infectious Diseases (CSH/CSID, 2022 version) and guidelines set by the American Association for the Study of Liver Diseases (AASLD, 2018 version). We retrospectively examined untreated CHB patients enrolled in the China Registry of Hepatitis B database. Patients’ clinical phases were determined as per CSH/CSID and AASLD. Liver fibrosis was estimated by FIB-4 and/or APRI. Among 3462 CHB patients, 56.9% and 41.7% fell into the grey zone based on AASLD and CSH/CSID. Compared with grey zone patients as per AASLD, those under CSH/CSID guidelines showed lower levels of median ALT (26.0 vs. 37.0 U/L, p < 0.001), AST (25.0 vs. 29.4 U/L, p < 0.001) and APRI (0.3 vs. 0.4, p < 0.001), and lower rates of advanced fibrosis estimated by APRI (7.9% vs. 11.4% p = 0.001), but comparable rates by FIB-4 (13.0% vs. 14.1%, p = 0.389). With the stepwise lowering of ALT upper limits of normal (ULN) values from 50/40 U/L for males/females to 40/40 U/L, 35/25 U/L and 30/19 U/L, the proportions of grey zone patients as per CSH/CSID declined from 46.7% to 41.7%, 34.3% and 28.8%, respectively, whereas they remained stable (55.7%, 56.2%, 56.9% and 57.0%) as per AASLD. Compared with the AASLD guidelines, CSH/CSID guidelines leave fewer and less severe patients in the grey zone. Lowering ALT ULN values reduces the number of grey zone patients as per CSH/CSID, but not under AASLD guidelines.

Abstract Background The present study was designed to investigate the protective effects and mechanisms of carnosine on lipopolysaccharide (LPS)-induced injury in Caenorhabditis elegans. Methods C. elegans individuals were stimulated for 24 h with LPS (100 μg/mL), with or without carnosine (0.1, 1, 10 mM). The survival rates and behaviors were determined. The activities of superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) were determined using the respective kits. Reverse transcription polymerase chain reaction (RT-PCR) was performed to validate the differential expression of sod-1, sod-2, sod-3, daf-16, ced-3, ced-9, sek-1, and pmk-1. Western blotting was used to determine the levels of SEK1, p38 mitogen-activated protein kinase (MAPK), cleaved caspase3, and Bcl-2. C. elegans sek-1 (km2) mutants and pmk-1 (km25) mutants were used to elucidate the role of the p38 MAPK signaling pathway. Results Carnosine improved the survival of LPS-treated C. elegans and rescued behavioral phenotypes. It also restrained oxidative stress by decreasing MDA levels and increasing SOD, GR, CAT, and GSH levels. RT-PCR results showed that carnosine treatment of wild-type C. elegans up-regulated the mRNA expression of the antioxidant-related genes sod-1, sod-2, sod-3, and daf-16. The expression of the anti-apoptosis-related gene ced-9 and apoptosis-related gene ced-3 was reversed by carnosine. In addition, carnosine treatment significantly decreased cleaved caspase3 levels and increased Bcl-2 levels in LPS-treated C. elegans. Apoptosis in the loss-of-function strains of the p38 MAPK signaling pathway was suppressed under LPS stress; however, the apoptotic effects of LPS were blocked in the sek-1 and pmk-1 mutants. The expression levels of sek-1 and pmk-1 mRNAs were up-regulated by LPS and reversed by carnosine. Finally, the expression of p-p38MAPK and SEK1 was significantly increased by LPS, which was reversed by carnosine. Conclusion Carnosine treatment protected against LPS injury by decreasing oxidative stress and inhibiting apoptosis through the p38 MAPK pathway.

ObjectiveTo retrospectively analyze the association of serum estradiol (E2) levels on human chorionic gonadotropin (hCG) trigger day and live birth rates (LBRs) in women undergoing fresh embryo transfer and not exhibiting polycystic ovary syndrome.DesignRetrospective cohort study.MethodsAnalysis of 13,950 patients who had fresh embryo transfer between December 2013 and December 2019. The main outcome measurement was LBRs. Multivariable regression analysis was performed to investigate associations between E2 levels on the hCG trigger day and LBRs. Stratification analysis was performed to test for effect modification in subgroups. Furthermore, a two-piecewise linear regression model was established to find nonlinear relationships.ResultsMultivariable regression analysis showed a significant association between serum E2 levels on the hCG trigger day and LBRs, adjusting for covariates [relative risk (RR) 1.027, 95% confidence interval (CI) 1.007, 1.049]. Stratification analysis showed that the LBRs were positively associated (RR 1.052, 95% CI 1.004, 1.102) with every 1 ng/ml increase of serum E2 on the hCG trigger day for the subgroup with low antral follicle counts on the trigger day. Specifically, a two-piecewise linear regression model showed that there was a positive association (RR 1.188, 95% CI 1.057, 1.334) between serum E2 and LBR for every increase of 1 ng/ml E2 when the concentration of serum E2 was lower than 2.1 ng/ml. However, there was no significant association (RR 1.002, 95% CI 0.971, 1.032) between E2 levels and LBRs when the concentration of E2 was higher than the 2.1ng/ml inflection point.ConclusionsSerum E2 levels on the hCG trigger day were segmentally connected with LBRs.

Serum hepatitis B virus pregenomic RNA (HBV pgRNA) is a potential biomarker that is correlated with covalently closed circular DNA. The long-term dynamics of HBV pgRNA in patients with chronic hepatitis B need to be explored. One hundred naïve nucleos(t)ide analog-treated patients with chronic hepatitis B were enrolled to analyze the dynamics of HBV pgRNA over 9 years. The positive rates of HBV pgRNAs declined gradually and showed biphasic kinetics. Serum HBV pgRNA levels in patients treated with entecavir became negative later than those treated with adefovir or lamivudine. Patients who remain positive for HBV pgRNA after 9 years of treatment may have higher viral transcription efficiencies. The reverse transcription efficiency of hepatitis B e-antigen (HBeAg)-positive patients was higher than that of HBeAg-negative patients at baseline and showed no difference after 24-week nucleos(t)ide analog treatment. The trajectory of serum HBV pgRNA-negative transformation differs in patients with different characteristics. Long-term dynamic monitoring of serum HBV pgRNA levels has significance in hepatitis B treatment.

Abstract Background Lipid profiles are declined in patients with viral liver cirrhosis and correlated with severity of liver disease. Hepatitis B virus (HBV) is the leading cause of liver cirrhosis in China. Our primary aim was to investigate whether serum lipids and lipoproteins associate with survival in patients with HBV-related cirrhosis and acute gastrointestinal bleeding, and develop a 6-week mortality risk score that incorporates it. Methods From January 2008 to December 2015, consecutive cirrhotic patients with acute gastrointestinal bleeding admitted to our hospital were evaluated and randomly divided into the derivation (n = 629) and validation (n = 314) cohorts. A logistic regression model was established to confirm the association between lipoprotein cholesterol and mortality. Accuracy to predict mortality were assessed by area under the receiver operating characteristic curves (AUROCs) and compared using the Hanley and McNeil test. Results Among study subjects, the 6-week mortality rate was 10.6%. High-density lipoprotein cholesterol (HDL-C) level was found to correlate most strongly with prognostic scores. On ROC analysis, HDL-C showed excellent diagnostic accuracy for 6-week mortality. Logistic regression analysis provided a simple algorithm based on the combined use of 4 variables (total bilirubin (TBIL), HDL-C, International normalized ratio, and hemoglobin), allowing accurate discrimination of 3 distinct prognostic subgroups with 1.7% (low risk), 12.3% (intermediate risk), and 56.9% (high risk) mortality. Its accuracy was significantly better than that of Child–Pugh, model of end-stage liver disease, albumin-bilirubin score, D’Amico model, Augustin model, AIMS65 score and Glasgow-Blatchford score. Baseline HDL-C values ≤ 0.54 mmol/L were associated with markedly lower 6-week survival. Comparable results were found in the validation set. Conclusion HDL-C is a potential indicator for the prognosis of patients with cirrhosis and acute gastrointestinal bleeding. The new algorithm based on HDL-C allowed an accurate predictive assessment of 6-week mortality after bleeding attack.

Abstract Background Transfer RNA-derived small RNAs (tsRNAs) are a recently discovered form of non-coding RNA capable of regulating myriad physiological processes. The role of tsRNAs in hMSC adipogenic differentiation, however, remains incompletely understood. The purpose of this study was to identify the novel tsRNA-16902 as a regulator of hMSC adipogenic differentiation. Methods In this study, we conducted transcriptomic sequencing of hMSCs after inducing their adipogenic differentiation, and we were thereby able to clarify the molecular mechanism underlying the role of tsRNA-16902 in this context via a series of molecular biology methods. Results When we knocked down tsRNA-16902 expression, this impaired hMSC adipogenic differentiation and associated marker gene expression. Bioinformatics analyses further revealed tsRNA-16902 to target retinoic acid receptor γ (RARγ). Luciferase reporter assays also confirmed the ability of tsRNA-16902 to bind to the RARγ 3′-untranslated region. Consistent with this, RARγ overexpression led to impaired hMSC adipogenesis. Further analyses revealed that Smad2/3 phosphorylation was increased in cells that either overexpressed RARγ or in which tsRNA-16902 had been knocked down. We also assessed the adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down and at the same time a Smad2/3 inhibitor was added to disrupt Smad2/3 phosphorylation. The adipogenic differentiation of hMSCs in which tsRNA-16902 was knocked down was further enhanced upon the addition of a Smad2/3 signaling inhibitor relative to tsRNA-16902 knockdown alone. Conclusions Through a comprehensive profiling analysis of tsRNAs that were differentially expressed in the context of hMSC adipogenic differentiation, we were able to identify tsRNA-16902 as a previously uncharacterized regulator of adipogenesis. tsRNA-16902 is able to regulate hMSC adipogenic differentiation by targeting RARγ via the Smad2/3 signaling pathway. Together, our results may thus highlight novel strategies of value for treating obesity.

Abstract Background Insulin resistance is an important defect associated with obesity and type 2 diabetes mellitus. Many studies have been reported that dietary fiber exerts beneficial metabolic effects. Resistant dextrin is a soluble fiber. The aim of this study was to investigate the effects of resistant dextrin on high-fat-high-fructose diet induced obese mice and to explore the underlying mechanisms. Methods Seventeen 4-week-old male C57BL/6 J mice were fed a normal diet (ND) or HFHFD for 22 weeks, and were gavaged with resistant dextrin (5 g/kg) for 10 weeks. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, serum fasting insulin (FINS) and serum biochemical parameters were determined, the contents of triglyceride (TG) and total cholesterol (TC) in liver tissues were determined by enzymatic method. The pathological changes in liver were detected by HE staining. Real time PCR and Western blot were used to detect the expression of insulin signaling pathway and the fatty acid β oxidation pathway related genes and proteins respectively. The gut microbiota were analyzed via 16 s rRNA sequencing. Results Resistant dextrin significantly decreased serum FINS, improved serum lipid profiles, reduced the contents of liver TG and TC. The insulin signaling pathway and the fatty acid β oxidation pathway were promoted. The abundance of metabolically beneficial bacteria such as Prevotella and Akkermansia in the intestinal flora of the resistant dextrin group were increased. Conclusions Resistant dextrin can significantly ameliorate liver insulin resistance, improve serum lipid levels, as well as reduce hepatic lipid deposition. The modulation of gut microbiota might be responsible for the beneficial effects of resistant dextrin.

Abstract Background The process of bone repair is heavily dependent on the ability of human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation. MicroRNAs have been shown to regulate this osteogenic process. This study aimed to investigate the role of miR-765 in the osteogenic differentiation of hMSCs. Methods We transfected hMSCs with lentiviral constructs to knock down or overexpress this miRNA, allowing us to assess its role in osteogenesis via assessing the expression of the relevant markers alkaline phosphatase (ALP), runt-related gene-2 (RUNX-2), and osteocalcin (OCN), with further functional measurements made via quantifying ALP activity and conducting Alizarin Red S staining. The targeting of the 3′-untranslated region (UTR) of BMP6 by miR-765 was examined via luciferase assay. We used hMSCs with altered miR-765 expression to assess p-Smad1/5/9 levels via Western blotting over the course of osteogenic differentiation. We also assessed the osteogenic differentiation of hMSCs in which miR-765 was knocked down and at the same time as a BMP/Smad signaling inhibitor was added to disrupt Smad1/5/9 phosphorylation. Results We found miR-765 overexpression to inhibit osteogenesis-associated gene upregulation during osteogenic differentiation of hMSCs, whereas knockdown of this miRNA was associated with increased expression of these genes. Using luciferase reporter assays, we confirmed direct miR-765 binding to the 3′-untranslated region (UTR) of BMP6. We also found that miR-765 overexpression reduced Smad1/5/9 phosphorylation, and knockdown of this miRNA enhanced this phosphorylation on BMP6/Smad1/5/9 signaling. The osteogenic differentiation of hMSCs in which miR-765 had been knocked down was further weakened upon the addition of a BMP/Smad signaling inhibitor relative to miR-765 knockdown alone. Conclusions Together, these results thus suggest that miR-765 is able to inhibit hMSC osteogenic differentiation by targeting BMP6 via regulation of the BMP6/Smad1/5/9 signaling pathway. Our findings may offer molecular insights of value for the development of novel therapeutic treatments for bone diseases including osteoporosis.

With the proliferation of renewable energy and electric vehicles (EVs), there have been increasing uncertainties in power systems. Identifying the influencing random variables will reduce the effort in uncertainty modeling and improve the controllability of power systems. In this paper, a density-based global sensitivity analysis (GSA) method is proposed to evaluate the influence of uncertainties on islanded microgrids (IMGs). Firstly, the maximum IMG loadability evaluation model is established to assess the distance from the current operation point to the critical operation point. Secondly, the Borgonovo method, which is a density-based GSA method, is used to evaluate the influence of input variables on IMG loadability. Thirdly, to improve GSA efficiency, a modified Kriging model is used to obtain a surrogate model of IMG loadability, and Borgonovo indices are calculated based on the surrogate model. Finally, the proposed method is tested on a 38-bus IMG system. Simulation results are compared with those considering other methods to validate the effectiveness of the proposed method. Energy storage systems are considered to diminish the influence of critical uncertainties on IMG operation.

Abstract Background Plasma albumin is reduced during inflammation. Obesity, a strong risk factor for type 2 diabetes (T2D), is associated with adipose tissue inflammation. However, whether albumin is associated with adipose tissue inflammation and whether it predicts T2D are unclear. Methods Adults (predominantly American Indian) from a longitudinal study were included. Macrophage content and gene expression related to recruitment/activation were measured from subcutaneous adipose tissue (n = 51). The relationship between plasma albumin and adiposity (dual-energy X-ray absorptiometry or hydrodensitometry), glucose (oral glucose tolerance test), insulin action (hyperinsulinemic-euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were evaluated (n = 422). Progression to T2D was evaluated by Cox regression (median follow-up 8.8 years; 102 progressors). Results Albumin was associated with macrophage markers including C1QB (r = − 0.30, p = 0.04), CSF1R (r = − 0.30, p = 0.03), and CD11b (r = − 0.36, p = 0.01). Albumin was inversely associated with body fat percentage (r = − 0.14, p = 0.003), fasting plasma glucose (r = − 0.17, p = 0.0003), and 2 h plasma glucose (r = − 0.11, p = 0.03), and was reduced in impaired glucose regulation compared with normal glucose regulation (mean ± SD: 39.4 ± 3.6 g/l and 40.1 ± 3.9 g/l, respectively; p = 0.049). Albumin predicted T2D, even after adjustment for confounders (HR, 0.75; 95% CI 0.58–0.96; p = 0.02; per one SD difference in albumin). Conclusions Reduced albumin is associated with an unfavorable metabolic profile, characterized by increased adipose tissue inflammation, adiposity, and glucose, and with an increased risk for T2D.

Gastrodia elata Blume (G. elata) is a valuable traditional Chinese medicine with neuroprotection, anti-inflammatory, and immune regulatory functions. MicroRNAs (miRNA) is a kind of endogenous noncoding small RNAs that plays distinctly important roles for gene regulation of organisms. So far, the research on G. elata is mainly focused on the pharmacological functions of the natural chemical ingredients, and the function of G. elata miRNA remains unknown. In this study, 5,718 known miRNAs and 38 novel miRNAs were identified by high-throughput sequencing from G. elata. Based on GO and KEGG analysis, we found that the human genes possibly regulated by G. elata miRNAs were related to the cell cycle, immune regulation, intercellular communication, etc. Furthermore, two novel miRNAs as Gas-miR01 and Gas-miR02 have stable and high expression in the medicinal tissues of G. elata. Further bioinformatics prediction showed that both Gas-miR01 and Gas-miR02 could target Homo sapiensA20 gene, furthermore, the dual-luciferase reporter gene assay and Western Blotting verified the interaction of Gas-miR01 or Gas-miR02 with A20. These evidences suggested that G. elata-unique miRNAs might be involved in certain physiological processes. The animal experiment showed that Gas-miR01 and Gas-miR02 could be detected in some tissues of mice by intragastric administration; meanwhile, the A20 expression in some tissues of mice was downregulated. These results supported for the functional study of G. elata miRNAs.

Abstract Background An understanding of the mechanism underlying adipogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) will provide new therapeutic approaches for many diseases, including osteoporosis. This study aimed to investigate the role of miR-431 in adipogenic differentiation of hMSCs. Methods hMSCs were induced for adipogenic differentiation and miR-431 was detected by polymerase chain reaction (PCR). hMSCs were transfected by miR-431 or small interfering RNA (siRNA) for insulin receptor substance 2 (IRS2). The expression of IRS2 was detected by PCR and Western blot analysis. The targeting of the 3′-untranslated region (UTR) of IRS2 by miR-431 was examined by luciferase assay. Results miR-431 expression was decreased during adipogenesis of hMSCs. Overexpression of miR-431 inhibited adipogenic differentiation, accompanied by the downregulation of CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), two key regulators of adipogenesis. Moreover, miR-431 decreased both protein and mRNA levels of IRS2. The expression of IRS2 was increased during adipogenic differentiation of hMSCs in conjunction with decreased levels of miR-431, and knockdown of IRS2 in hMSCs inhibited adipogenic differentiation. Luciferase assay confirmed that miR-431 targeted the 3′-UTR of IRS2 in hMSCs. Conclusions This is the first study to show that miR-431 inhibits adipogenic differentiation of hMSCs via targeting IRS2.

The ac-dc hybrid distribution network is a credible path for the future evolution of distribution network. State estimation is a paramount foundation for the safe and stable operation of the complex distribution network. The application of the centralized state estimation method in an ac-dc distribution network has some obstacles, such as low computational efficiency, large communication capacity, and privacy protection problem. Based on the three-stage state estimation theory, this paper established a three-stage state estimation model for the ac-dc hybrid distribution network integrating supervisory control and data acquisition system and phasor measurement unit. The proposed three-stage estimation model achieves linearization of the nonlinear state estimation for the ac-dc hybrid distribution network. That is, the first and third stages simply solve the linear state estimation problem, and the second stage is a one-step nonlinear transform. Moreover, the alternating direction method of multipliers (ADMM) is applied to solving the distributed problem. Thus, an accurate and efficient three-stage distributed state estimation method for the ac-dc hybrid distribution network is proposed. In this method, ac subsystems and dc subsystems execute state estimation tasks based on local information and eventually achieve the overall consistency of the system state estimation through the transfer iteration of the boundary information, respectively. The combination of bilinear theory and ADMM ensures the convergence of distributed state estimation while improving computational efficiency. The simulation results verified the advantage of the proposal over the existing methods in many aspects.

With the proliferation of renewable energy, the uncertainty has challenged the continuous operation of microgrids; thus, it is of importance to tackle uncertainties in power system operation. In this paper, a global sensitivity analysis (GSA) method is proposed to evaluate the influence of uncertainties on the power flow of islanded microgrids (IMGs). First, a probabilistic power flow model for IMGs is established considering the droop-controlled distributed generation units and the uncertainties of renewable energy generation output and load demands. Then, the global sensitivity analysis is introduced to identify important variables that affect IMG power flow. In addition to conventional GSA indices, the Shapley value-based GSA index is designed to evaluate the influence of correlated input variables. Moreover, the sparse polynomial chaos expansion is used to establish the surrogate models of IMG power flow, which improves the efficiency of GSA. Finally, the proposed method is tested on the 33-bus and 69-bus IMG systems, and the simulation results are compared with those considering other methods. The rankings of random input variables that affect IMG power flow are given, and the influence of correlation between different variables is discussed.

Feature subset selection is a key problem in such data mining classification tasks.In practice,the filter methods ignore the correlations between genes which are prevalent in gene expression data,additionally,existing methods are not specially conceived to handle the small sample size of the data which is one of the main causes of feature selection instability.In order to deal with these issues,a new hybrid,filter wrapper was proposed,and a cooperative subset search(CSS),was then researched with a classifier algorithm to represent an evaluation system of wrappers.The method was experimentally tested and compared with state-of-the-art algorithms based on several high-dimension allow sample size cancer data sets.Results show that the proposed approach outperforms other methods in terms of accuracy and stability of the selected subset.

This paper employs an efficacious analytical tool, adaptive simplified human learning optimization (ASHLO) algorithm, to solve optimal power flow (OPF) problem in AC/DC hybrid power system, considering valve-point loading effects of generators, carbon tax, and prohibited operating zones of generators, respectively. ASHLO algorithm, involves random learning operator, individual learning operator, social learning operator and adaptive strategies. To compare and analyze the computation performance of the ASHLO method, the proposed ASHLO method and other heuristic intelligent optimization methods are employed to solve OPF problem on the modified IEEE 30-bus and 118-bus AC/DC hybrid test system. Numerical results indicate that the ASHLO method has good convergent property and robustness. Meanwhile, the impacts of wind speeds and locations of HVDC transmission line integrated into the AC network on the OPF results are systematically analyzed.

Abstract The ubiquitin-specific protease 22 (USP22) is an oncogene and its expression is upregulated in many types of cancer. In the nucleus, USP22 functions as one subunit of the SAGA to regulate gene transcription. However, the genome-wide USP22 binding sites and its direct target genes are yet clear. In this study, we characterized the potential genomic binding sites of UPS22 and GCN5 by ChIP-seq using specific antibodies in HeLa cells. There were 408 overlapping putative target genes bound by both USP22 and GCN5. Motif analysis showed that the sequences bound by USP22 and GCN5 shared two common motifs. Gene ontology (GO) and pathway analysis indicated that the genes targeted by USP22 and GCN5 were involved in different physiological processes and pathways. Further RNA-seq, GO and pathway analyses revealed that knockdown of UPS22 induced differential expression of many genes that participated in diverse physiological processes, such as metabolic process. Integration of ChIP-seq and RNA-seq data revealed that UPS22 bound to the promoters of 56 genes. These findings may provide new insights into the regulation of USP22 on gene expression during the development of cervical cancer.

Abstract The original article [1] contains an error in spelling of author, Yanling Wang’s name. The correct version can instead be viewed in this Correction article.

The efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.Direct sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.The incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.Pre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.

Skin wound healing is a complex and dynamic process that involves angiogenesis and growth factor secretion. Newly formed vessels can provide nutrition and oxygen for skin wound healing. Growth factors in skin wounds are important for keratinocytes and fibroblasts proliferation, epithelialization, extracellular matrix remodeling, and angiogenesis, which accelerate skin wound healing. Therefore, treatment strategies that enhance angiogenesis and growth factors secretion in skin wounds can accelerate skin wound healing. This study investigated the effects of a SIKVAV (Ser-Ile-Lys-Val-Ala-Val) peptide-modified chitosan hydrogel on skin wound healing. Hematoxylin and eosin (H&E) staining demonstrated that the SIKVAV-modified chitosan hydrogel accelerated the re-epithelialization of wounds compared with that seen in the negative and positive controls. Masson’s trichrome staining showed that more collagen fibers were deposited in the skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. Immunohistochemistry assays demonstrated that more myofibroblasts were deposited and more angiogenesis occurred in skin wounds treated with the SIKVAV-modified chitosan hydrogel than in the negative and positive controls. In addition, ELISA assays showed that the SIKVAV-modified chitosan hydrogels promoted the secretion of growth factors in skin wounds. Taken together, these results suggest that the SIKVAV-modified chitosan hydrogel has the potential to be developed as synthesized biomaterials for the treatment of skin wounds.

OBJECTIVE: Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the mechanisms underlying this effect are still unknown. In this study, the ability of insulin to protect apoptotic cardiomyocytes from hypoxia/reoxygenation injury using the sphingosine kinase/sphingosine 1-phosphate axis was investigated. METHODS AND RESULTS: Rat cardiomyocytes were isolated and subjected to hypoxia and reoxygenation. [γ-32P] ATP was used to assess sphingosine kinase activity. Insulin was found to increase sphingosine kinase activity. Immunocytochemistry and Western blot analysis showed changes in the subcellular location of sphingosine kinase 1 from cytosol to the membrane in cardiomyocytes. Insulin caused cardiomyocytes to accumulate of S1P in a dose-dependent manner. FRET efficiency showed that insulin also transactivates the S1P1 receptor. TUNEL staining showed that administration of insulin during reoxygenation could to reduce the rate of reoxygenation-induced apoptosis, which is a requirement for SphK 1 activity. It also reduced the rate of activation of the S1P receptor and inhibited hypoxia/reoxygenation-induced cell death in cardiomyocytes. CONCLUSION: The sphingosine kinase 1/sphingosine 1-phosphate/S1P receptor axis is one pathway through which insulin protects rat cardiomyocytes from apoptosis induced by hypoxia/reoxygenation injury.

This article collected 199 cases of domestic natural gas pipeline leakage accidents, and used the mathematical methods and SPSS statistical analysis software to analysis these accident cases. Based on the analysis of accidents statistics and disaster reduction factors, the natural gas pipeline risk rating assessment method based on accident statistics was proposed according to Risk value method and Risk matrix analysis. Taking the gas pipelines in a certain city for example, the risk grade of the pipeline was analyzed by the method proposed in this article, and more rigorous and effective measures to reduce the pipeline risk were proposed.

BACKGROUND: Due to shared transmission routes, hepatitis C virus (HCV) infection is highly prevalent among people infected with human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is associated with hepatotoxicity, leading to the negative effects on patients with HIV/HCV co-infection. In order to provide valuable information for HCV management in this particular population, we investigated the HCV genotypes in HIV-infected individuals from Henan and Guangxi, the two provinces with the most HIV-infected cases in China. METHODS: Individuals, who acquired HIV infection through various risk routes, were recruited from Henan and Guangxi. Test of antibodies against HCV (anti-HCV) was conducted, and detection of HCV RNA was performed by PCR amplification. HCV subtypes were determined by direct sequencing of amplicons, followed by phylogenetic analysis. RESULTS: We recruited a total of 1,112 HIV-infected people in this present study. Anti-HCV was detected from 218 (50.1%) patients from Henan and 81 (12.0%) patients from Guangxi, respectively. The highest prevalence of HIV/HCV co-infection was observed from FBDs (former blood donors) (87.2%) in Henan and IDUs (intravenous drug users) (81.8%) in Guangxi, respectively. The seroprevalence rate of HCV among people with sexual contact was significantly higher in Henan than in Guangxi (18.7% vs. 3.5%, P