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Sanghuang as a medicinal fungus in China has a history of more than 2000 years, and is known as the “forest gold”. Most notably, the polysaccharides of Sanghuangporus sp. have attracted widespread attention due to their significant bioactivity in recent years. At present, extensive studies are being carried out on the extraction methods, structural characterization, and activity evaluation of polysaccharides. Here, we aimed to evaluate the structure and bioactivity of LEPS-1, an exopolysaccharide derived from the S. sanghuang JM-1 strain. The structure was elucidated by chromatography/spectral methods and hydrolyzation, and the solubility, the antioxidant activity, hypoglycemic activity and immunomodulatory activity were investigated. Results showed that LEPS-1 contained a →2)-α-Manp(1→6)-α-Galp(1→[2)-α-Manp(1→]n→2,6)-α-Manp(1→6,2)-α-Manp(1→3)-α-Manp(1→ backbone substituted at the O-6 and O-2 positions with side chains. These two branching fragments were β-Manp(1→. The molecular weight of LEPS-1 is 36.131 kDa. The results of biological activity analysis suggested that LEPS-1 was easily soluble in water, with reducing capability and DPPH radical scavenging capability. Furthermore, the IC50 values of LEPS-1 against α-amylase and α-glucosidase were 0.96 mg/mL and 1.92 mg/mL. LEPS-1 stimulated RAW264.7 cells to release NO, TNF-α and IL-6 with no cytotoxicity, showing potent potential for immunomodulatory activity. These findings describe a potential natural exopolysaccharide with medicinal value and a basis for the development of S. sanghuang exopolysaccharides.

[Introduction] Large-scale connection of wind power to the power grid poses great challenges to the stability (especially frequency stability) of grid operation.In order to solve the problem of inadequate frequency regulation capability caused by large-scale connection of wind power to the power grid and improve the frequency adaptability of wind power grid connection, wind turbines need to have frequency regulation function and response timeliness. [Method] This paper adopted a frequency regulation system scheme based on rotor kinetic energy and pitch angle reserve, which could provide active support for the power grid quickly and accurately during the power grid frequency change. Firstly, the main control algorithm was designed based on the theoretical analysis of inertia response and primary frequency regulation algorithm logic. Then, the functional verification was carried out on the co-simulation platform. Finally, the actual test was carried out in a project.[Result] The simulation and test results showed that the frequency regulation system scheme based on rotor kinetic energy and pitch angle reserve could cope with a variety of grid frequency changes and quickly provided active support. [Conclusion] The frequency regulation system scheme of wind turbines can perform a fast inertia response (with the response time less than 500 ms) and primary frequency regulation response (with the response time less than 5 s) under various frequency change conditions and provide active support for the power grid, which can help recover the grid frequency and effectively improve the frequency adaptability of wind turbines.

Abstract Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. Methods Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. Results The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of

In order to reduce pollution caused by ship emissions, the International Maritime Organization (IMO) implemented sulfur emission control areas (SECAs). In comparison to ordinary vessels, cruise ships with dual attributes of transportation and tourism generate a greater amount of marine pollution, which poses a significant threat to the marine environment in both berthing ports and the sailing area. In light of the fierce competition of the cruise tourism market, cruise lines are looking for strategies, such as designing more attractive cruise routes, to maintain their core competencies under the emission control policy. In order to achieve this goal, this paper presents a mixed-integer non-linear programming (MINP) model with two objectives and is derived from the traditional route optimization problem. The primary objective is to optimize the route and speed of a cruise liner, while simultaneously enhancing route competitiveness and minimizing carbon emissions both within and outside the SECAs. Subsequently, the multi-objective particle swarm optimization (MOPSO) algorithm was used to reach the objective, and simulations were carried out to verify the effectiveness of the model and method. The results show that speed and sailing route optimization can affect carbon emissions. This paper has a certain application value and guiding significance for cruise line decision makers that will be beneficial for the environment.

For the rapid development of the cruise industry, the cruise disaster relief supply chain has attracted extensive attention, especially because COVID-19 cases on international cruise ships occurred. In this paper, we propose an idea of coordination layout for cruise ship emergency supplies, the problem optimized two objective functions of maximizing coverage satisfaction and minimizing the total cost, addressing the low efficiency of resource utilization at the same. By applying to cruise ship emergency supplies layout of Northeast Asia cruise port group system, using expert scoring method and AHP to evaluate cruise port security vulnerability. The NSGA-II algorithm is used to solve the multi-objective programming model. A numerical example shows that the optimization design model and method are valid and feasible, and the algorithm is efficient for solving the above collaborative location and allocation problem of sectional reserves, which can also offer a variety of decision-making options.

[Introduction] In order to improve the flexible fault ride through (FFRT) capability of semi-direct drive wind power system, this paper proposes an improved grid-side control strategy with reactive power priority. [Method] Based on the analysis of the traditional grid side control strategy, reactive power priority control was added to the traditional grid side control according to the latest test rules of fault voltage ride through capability, and reactive current was injected into the grid to support the voltage recovery during the transient faults of the grid. According to the improved grid-side control strategy, the FFRT simulation operation of wind turbine was realized by using chopper circuits combined with the improved grid-side control strategy when the deep sag and rise of the grid was realized. Combined with the 6 MW semi-direct drive wind turbine of a certain project, the fault voltage ride field test was carried out by using mobile FFRT test equipment. [Results] The test and simulation results show that the improved grid-side control strategy can improve FFRT operation of semi-direct drive wind power system and stable control of reactive current. [Conclusion] The improved grid-side control strategy can give priority to injecting the corresponding stable reactive current into the grid under various symmetric low voltage/high voltage fault conditions and asymmetric high voltage fault conditions, which can assist the voltage recovery of the grid and improve the FFRT capacity of the semi-direct drive wind power system.

BackgroundCytopenia is a frequent complication among HIV-infected patients who require hospitalization. It can have a negative impact on the treatment outcomes for these patients. However, by leveraging machine learning techniques and electronic medical records, a predictive model can be developed to evaluate the risk of cytopenia during hospitalization in HIV patients. Such a model is crucial for designing a more individualized and evidence-based treatment strategy for HIV patients.MethodThe present study was conducted on HIV patients who were admitted to Guangxi Chest Hospital between June 2016 and October 2021. We extracted a total of 66 clinical features from the electronic medical records and employed them to train five machine learning prediction models (artificial neural network [ANN], adaptive boosting [AdaBoost], k-nearest neighbour [KNN] and support vector machine [SVM], decision tree [DT]). The models were tested using 20% of the data. The performance of the models was evaluated using indicators such as the area under the receiver operating characteristic curve (AUC). The best predictive models were interpreted using the shapley additive explanation (SHAP).ResultThe ANN models have better predictive power. According to the SHAP interpretation of the ANN model, hypoproteinemia and cancer were the most important predictive features of cytopenia in HIV hospitalized patients. Meanwhile, the lower hemoglobin-to-RDW ratio (HGB/RDW), low-density lipoprotein cholesterol (LDL-C) levels, CD4+ T cell counts, and creatinine clearance (Ccr) levels increase the risk of cytopenia in HIV hospitalized patients.ConclusionThe present study constructed a risk prediction model for cytopenia in HIV patients during hospitalization with machine learning and electronic medical record information. The prediction model is important for the rational management of HIV hospitalized patients and the personalized treatment plan setting.

Abstract Background Real‐world application of osimertinib with antiangiogenic agents in non‐small cell lung cancer (NSCLC) is common, but the efficacy data are rarely reported. Methods To obtain an objective efficacy report of different real‐world treatment models of osimertinib and antiangiogenic agents. Results A total of 54 patients with NSCLC were enrolled into the study. Twelve (22.2%) who received a combination of antiangiogenic agents, when there was a trend of osimertinib resistance but did not reach imageology progressive disease (PD), were assigned to Group A, with a median overall survival (OS) and progression‐free survival (PFS) of 48.0 (95% CI, not reached) and 21.0 (95% CI: 16.7–25.3) months, respectively. Thirty (55.6%) who received a combination of antiangiogenic agents when there was imageology PD during treatment with osimertinib were assigned to Group B, with a median OS and PFS of 31.8 (95% CI: 26.6–37.1) and 9.2 (95% CI: 5.9–12.6) months, respectively. Twelve (22.2%) who received a combination of antiangiogenic agents at the initial treatment with osimertinib were assigned to Group C, with a median OS and PFS of 28.5 (95% CI: 15.2–41.8) and 15.3 (95% CI: 7.9–22.7) months, respectively. Patients in Group A achieved a significant prolonged median PFS (p

IntroductionThe experiment was conducted to evaluate the effects of Ganoderma lingzhi culture (GLC) as a fermented feed on growth performance, serum biochemical profile, meat quality, and intestinal morphology and microbiota in Sanhuang broilers. In addition, the association between gut bacteria and metabolites was investigated via untargeted metabolomic analysis.MethodsA total of 192 Sanhuang broilers (112 days old) with an initial body weight of 1.62 ± 0.19 kg were randomly allocated to four treatments, six replicate pens per treatment with 8 broilers per pen. The four treatments contain a control diet (corn-soybean meal basal diet, CON), a positive control diet (basal diet + 75 mg/kg chlortetracycline, PCON), and the experimental diets supplemented with 1.5 and 3% of GLC, respectively. The trial includes phase 1 (day 1–28) and phase 2 (day 29–56).ResultsThe results showed that broilers in PCON and GLC-added treatments showed a lower FCR (P < 0.05) in phase 2 and overall period and a higher ADG (P < 0.05) in phase 2. On day 56, the concentrations of serum SOD (P < 0.05), and HDL (P < 0.05) and cecal SCFA contents (P < 0.05) were increased in broilers fed GLC diets. Broilers fed GLC also showed a higher microbiota diversity and an elevated abundance of SCFA-related bacteria in the caecum. The association between intestinal bacteria and metabolites was investigated via correlation analysis. The differential metabolites in the caecum, such as L-beta-aspartyl-L-aspartic acid and nicotinamide riboside, were identified.ConclusionIn summary, dietary GCL supplementation could increase growth performance to some extent. Moreover, GLC might benefit broilers' health by improving serum HDL content, antioxidant status, SCFAs contents, bacterial diversity, and probiotic proliferation in the caecum.

Abstract Aim There are still patients of stage I lung adenocarcinoma (ADC) suffering from local or distant recurrence. Herein we conducted a meta‐analysis to investigate the prognostic value of tumor spread through air space (STAS), a new form of invasion pattern, in patients with pathologically confirmed stage I lung ADC. Methods Related literature was searched using PubMed, Embase, Cochrane Library, and Web of Science databases from the inception dates to September 4, 2021. Recurrence‐free survival (RFS) and overall survival (OS) were set as primary outcome endpoints. In addition, subgroup analyses on operation mode, edition of the American Joint Committee on Cancer TNM staging, sample size, and research regions were also investigated. Results A total of 17 studies involving 9785 patients were included. The presence of STAS was detected in 31.2% of patients and was associated with poor RFS (adjusted hazard ratio [HR] = 1.93, p

ObjectiveThis study aimed to clarify the incidence trend of all-stage colorectal neuroendocrine neoplasms (CRNENs), overall survival (OS), and disease-specific survival (DSS) of patients with stage II-IV CRNENs, and to establish relevant nomograms for risk stratification.MethodsAmong all patients diagnosed with CRNENs in the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2019, temporal trends in incidence were assessed. Clinical data of 668 patients with stage II-IV CRNENs from 2010 to 2016 were extracted for survival analysis. Patients were randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Univariate and multivariate cox regression analyses were utilized to identify independent prognostic factors affecting OS outcomes. Competing risk analysis was applied to investigate risk factors related to the DSS of CRNENs. Two nomograms specifically for OS and DSS were developed for patients with stage II-IV CRNENs, their prognostic capabilities were evaluated using calibration curves, receiver operating characteristic (ROC) curves, the time-dependent area under the curve (AUC), and decision-curve analysis (DCA). Our hospital’s independent cohort of 62 patients with CRNENs was used as the external validation cohort.ResultsIn the period of 1975-2019, the incidence of CRNENs increased steadily with an annual percentage change (APC) of 4.50 (95% confidence interval [CI]: 3.90–5.11, P < 0.05). In total, 668 patients with stage II-IV CRNENs were included in the survival analysis from 2010 and 2016. Independent adverse prognostic factors for both OS and DSS of CRNENs prior treatment included grade III/IV (HR for OS: 4.66, 95%CI: 2.92-7.42; HR for DSS: 4.79, 95%CI: 4.27-5.31), higher TNM stage ([stage III vs stage II] HR for OS: 2.22, 95%CI: 1.25-3.94; HR for DSS: 2.69, 95%CI: 1.96-3.42. [stage IV vs stage II] HR for OS: 3.99, 95%CI: 2.03-7.83; HR for DSS: 4.96, 95%CI: 4.14-5.78), liver metastasis (HR for OS: 1.61, 95%CI: 1.03-2.51; HR for DSS: 1.86, 95%CI: 1.39-2.32), and brain metastasis (HR for OS: 4.57, 95%CI: 1.66-12.58; HR for DSS: 5.01, 95%CI: 4.15-5.87). Advanced age was also identified as a risk factor for OS (HR: 2.03, 95%CI: 1.5-2.76) but not DSS. In terms of treatment, surgery can significantly prolong OS (HR: 0.62, 95%CI: 0.44-0.86) and DSS (HR: 0.67, 95%CI: 0.29-1.05), but chemotherapy and radiation failed to show significance. The respective nomograms for OS and DSS for stage II-IV CRNENs demonstrated high accuracy and robust prediction value in predicting 1-year, 3-year, and 5-year OS and DSS outcomes in training, internal validation, and external validation cohorts. Besides, two online tools regarding OS and DSS prediction were established, facilitating nomogram score calculation, risk group determination, as well as survival prediction for each individual patient.ConclusionOver the past 40 years, the incidence of CRNENs presented increased steadily, along with improved survival outcomes. Grade III-IV, higher TNM stage, liver metastasis, brain metastasis, and without receiving surgery were found to be associated with worse OS and DSS. Advanced age was a risk factor for OS but not DSS. Nomograms for patients with stage II-IV stage CRNENs are capable of predicting the 1-, 3-, and 5-year OS and DSS rates with high accuracy, and realize risk stratification.

To establish a suitable pure electric bus arrival time prediction model, this paper takes pure electric bus as the research object. Based on the analysis of the influencing factors of the arrival time of the pure electric bus, the BP neural network arrival time prediction model optimized by the firefly algorithm (FA-BP prediction model) is established by selecting vehicle type, SOC value, battery age, and time as input conditions. The model is trained and tested by using bus operation data. The root mean square error of the Kalman filter model is 0.351, of the BP neural network model is 0.059, and of the FA-BP prediction model is 0.04. The results show that the model in this paper effectively improves the prediction accuracy and has good reliability and feasibility. It can provide some theoretical references for pure electric bus operation and managers and provide some basis for improving bus reliability.

Abstract Background Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive disease with poor survival, and platinum-etoposide chemotherapy is indicated as the mainstay of treatment. In this study, we compared the efficacy and safety between the cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC) regimens. Methods A total of 1305 patients with previously untreated ES-SCLC were included in this study. Data from five trials were collected from the public database Project Data Sphere. Survival analysis and adverse events (AEs) analysis were conducted. Results Of the 1305 patients, 800 received the EC regimen whereas 505 received the EP regimen as their front-line treatment. Overall, the median progression-free survival (PFS) and the median overall survival (OS) were 172 and 289 days, respectively. The EP and EC treatment groups did not have significantly different PFS or OS. After adjusting for age, sex, body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) performance status (PS), the EP regimen was independently associated with better PFS (hazard ratio [HR] = 0.76, 95% CI = 0.63–0.92, p = 0.0041) and OS (HR = 0.79, 95% CI = 0.64–0.97, p = 0.0220) among patients who were overweight and obese (BMI ≥ 25 kg/m2). In the safety analysis, patients who received the EC treatment experienced significantly more grade ≥ 3 AEs (n = 599, 74.9%) than those who received the EP treatment (n = 337, 66.7%; p = 0.002). Furthermore, the EC regimen was associated with a higher risk of grade 3–4 neutropaenia (p = 0.001), thrombocytopaenia (p

45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.

The distributed photovoltaic power generation is an important way to make use of solar energy in cities. China issues a series of policies to support the development of distributed photovoltaics in law, electricity price, grid connection standard, project management, financial support and so on. However, there are still some defects in policies and market mechanism. China creates a competitive market with a significant number of projects of distributed photovoltaic power through the reform of the electricity market, yet substantial drawbacks of the corresponding investment subsidies prevent distributed photovoltaic power from rapidly developing. This paper summarizes the status quo of China’s distributed photovoltaic power development, given its long-term plan, presents excellences and shortcomings of the existing policy system, and looks into the supporting policies and implementation paths for China’s distributed photovoltaic power in different stages. Innovative business models and financial support models are conducive to the development of distributed photovoltaic power. Financial innovation methods such as crowd funding and asset securitization should be encouraged to develop a sound risk assessment mechanism for projects, involve insurance institutions, and establish a risk sharing mechanism. In the context of a series of supporting policies, the distributed photovoltaic power in China will move towards market-oriented standardization for a healthier and more stable development.

Background Although tobacco exposure remains the most important risk factor of tumorigenesis of small cell lung cancer (SCLC), its prognostic value has failed to reach a consensus until now. Accordingly, we conducted a meta‐analysis to investigate the prognostic value of pretreatment smoking status (smokers vs. never‐smokers) in SCLC. Methods The four databases PubMed, Medline, Embase, and Cochrane library were searched to identify the relevant literature from the inception dates to 24 June 2020. The primary outcome was overall survival (OS), and the secondary endpoint was progression‐free survival (PFS). The hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to assess the relationship between pretreatment smoking status and patient survival. Sensitivity analysis was performed to assess the stability of the pooled results. Begg's funnel plot and Egger's test were applied to detect the publication bias. All statistical analyses were performed using RevMan V.5.3 and STATA version 15.0 software. Results A total of 27 studies involving 12 047 patients with SCLC (9137 smokers and 2910 never‐smokers) were included in this meta‐analysis. The results showed that smoking history was closely related to poorer survival outcome (OS: HR = 1.17, 95% CI: 1.12–1.23, P

Abstract Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient’s genetic alteration features. TKIs have dramatically improved patients’ survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies.

The continuous development of nanotechnology has brought new trends of thought and new impetus to sculpture art. In the field of microengraving, people usually use two-photon engraving technology, but not every particle conforms to the engraving process. ZnO nanoparticles have a high refractive index and are extremely flexible, making them the material of choice for laser engraving. This article aims to investigate whether the incorporation of high-refractive-index flexible nanoparticles into engraving techniques can significantly improve the functional properties of products. This paper firstly introduces the preparation methods of common nanoparticle laser engraving materials and then describes simple micro-nano sculptures on this basis. Finally, experiments on the transmittance and refractive index of ZnO nanoparticles are carried out. The experimental results show that the refractive index and transmittance of this material are 1.7 and 1.039, respectively, which is very suitable for laser engraving.

Water is a limited and valuable resource. Singapore has four national sources of water supply, one of which is natural precipitation. Pollutants collected in stormwater runoff are deposited into drainage systems and reservoirs. Major nutrient pollutants found in local stormwater runoff include nitrate and phosphate, which may cause eutrophication. Bioretention systems are efficient in removing these pollutants in the presence of plants. This paper discusses plant traits that can enhance the phytoremediation of nutrient pollutants in stormwater runoff for application in bioretention systems. The plant species studied showed variations in chlorophyll florescence, leaf greenness, biomass production, and nitrate and phosphate removal. In general, dry biomass was moderately correlated to nitrate and phosphate removal (r = 0.339–0.501). Root, leaf, and total dry biomass of the native tree species showed a moderate to strong correlation with nitrate removal (r = 0.811, 0.657, and 0.727, respectively). Leaf dry biomass of fast-growing plants also showed a moderate to strong relationship with the removal of both pollutants (r = 0.707 and 0.609, respectively). Root dry biomass of slow-growing plants showed a strong relationship with phosphate removal (r = 0.707), but the correlation was weaker for nitrate removal (r = 0.557). These results are valuable for choosing plants for application in bioretention systems. Keywords: Nitrogen, Phosphorus, Plant traits, Bioretention system, Stormwater, Tropical plant, Nutrient pollutant, Native plants

According to the characteristics of cruise ship supply logistics, using a mixed-integer linear programming model (MILP), we describe the location-distribution and time utility requirements, in which the capacity constraints of the distribution centres and time window are considered, in order to minimize the sum of fixed cost, variable cost, distribution cost between nodes and time penalty cost. Further, a ‘two-stage’ method is suggested to solve the MILP problem. In the first stage, the Benders decomposition algorithm is adopted to determine the location of the distribution centres, flow allocation and shipment sizes on each link. Then IBM ILOG CPLEX optimization studio software is used to get the optimal value of the distribution schedule of ship suppliers in the second stage. Finally, the proposed method is verified by a study simulation.

Background: In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020. Methods: We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov. Findings: A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013–2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing (n=273) and Shanghai (n=257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors. Interpretation: In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy. Funding: This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).

Since its first appearance in Wuhan, China, severe acute respiratory syndrome coronavirus 2 has rapidly spread throughout the world and has become a global pandemic. It remains unclear whether people living with human immunodeficiency virus are at an increased risk of coronavirus disease 2019 and severe disease manifestation; until now, the evidence regarding the outcomes from severe acute respiratory syndrome coronavirus 2 infection in people living with human immunodeficiency virus is still limited and conflicting. The clinical characteristics of seven patients of family cluster-onset coronavirus disease 2019 were reported, including the immune characteristics of one patient of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection. In the patients of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection, about 2 weeks after infection, it was observed that CD4 and CD8 count showed a downward trend and that of CD8 is more obvious; at the same time, lymphocytes showed a slight increase. CD4, CD8, and lymphocytes are in the plateau period from the second week to the fourth week. About 4 weeks after infection, all showed an increase, in which anti-coronavirus combined with antiviral therapy were given. The time for Nucleic Acid Testing to present as negative was 51 days. The other six patients in the family were non–human immunodeficiency virus infected, the familial cluster received parallel treatment, and the median time for the Nucleic Acid Testing to present as negative was 29 days. The patient of human immunodeficiency virus/severe acute respiratory syndrome coronavirus 2 coinfection presents an immune state of CD4’s and CD8’s dual lymphatic depletion. Human immunodeficiency virus should still be regarded as an important factor in future risk stratification models for coronavirus disease 2019.

To overcome challenges like market dynamic configuration, information integration, and quick response, it is necessary to build an efficient, stable, and well-coordinated supply chain relationship for cruise ship supply. This requires building of a solid evaluation index system of logistics service providers (LSPs) in the cruise ship supply chain. In this paper, we introduce an evaluation index system that consists of four dimensions, based on the characteristics of cruise ship supply and the connotation and type of cruise ship supply LSPs. The four dimensions are business level, collaborative capacity, service price, and information level, including ten subcriteria. We first establish an evaluation decision model for the interdependence and feedback relationship between the criteria by using analytic network process (ANP) for weight definition of each index; then, we use Super Decisions software to simulate the results, combine RBF neural network training and validation, and extract implicit knowledge and laws. We propose an incremental algorithm that can effectively avoid the influence of subjective factors and increase the dynamic nature of evaluation. The results show that the ANP-RBF method has strong practicability in the evaluation of cruise ship supply LSPs.

Selenium Auricularia cornea culture (SAC) is a new source of organic selenium. Two experiments were conducted to determine the available energy of SAC fed to pigs and to evaluate the effects of dietary SAC supplementation on growth performance, serum biochemical profiles, fecal short chain fatty acids (SCFA), meat quality, tissue selenium concentration, and oxidative stability of fresh meat in growing-finishing pigs. In Experiment (Exp.) 1, 12 barrows with average body weight (BW) of 42.40 ± 5.30 kg were randomly allotted to two groups and fed the basal diet and SAC-supplemented diet, individually. In Exp. 2, 96 growing-finishing pigs (BW: 91.96 ± 7.55 kg) were grouped into four dietary treatments; each treatment contained six replicates with four pigs per replicate. The four treatments fed a control diet and three experimental diets supplemented with 0.6%, 1.2%, and 2.4% SAC, respectively. The trial lasted for 45 days. The results revealed that digestible energy (DE) of SAC was 11.21 MJ/kg. The average daily gain (ADG) was improved in pigs fed 1.2% and 2.4% SAC during day 24 to 45 and the overall period. Dietary 1.2% and 2.4% SAC supplementation had a lower F/G (p < 0.05) than the control diet during different stages. Dietary SAC supplementation increased fecal butyrate contents (p < 0.05), and pigs fed 1.2% and 2.4% SAC diets had a higher MCT1 mRNA expression (p = 0.04) in the colon. Pigs fed 2.4% SAC had higher GSH-Px contents (p < 0.05) in serum, liver, and longissimus dorsi muscle (LDM) than those in the control group. The 2.4% SAC-supplemented group revealed a higher Se content (p < 0.05) in LDM and a lower MDA concentration (p < 0.05) in fresh meat during the simulated retail display on day six. In conclusion, this study suggested that SAC was more effective in improving growth, enhancing the antioxidant status, depositing Se in muscle, and increasing meat oxidative stability of pigs.

Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC).A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005).The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

With the deregulation of electricity market, generation companies must take part in strategic bidding by offering its bidding quantity and bidding price in a day-ahead electricity wholesale market to sell their electricity. This paper studies the strategic bidding of a generation company with thermal power units and wind farms. This company is assumed to be a price-maker, which indicates that its installed capacity is high enough to affect the market-clearing price in the electricity wholesale market. The relationship between the bidding quantity of the generation company and market-clearing price is then studied. The uncertainty of wind power is considered and modeled through a set of discrete scenarios. A scenario-based two-stage stochastic bidding model is then provided. In the first stage, the decision-maker determines the bidding quantity in each time period. In the second stage, the decision-maker optimizes the unit commitment in each wind power scenario based on the bidding quantity in the first stage. The proposed two-stage stochastic optimization model is an NP-hard problem with high dimensions. To tackle the problem of “curses-of-dimensionality„ caused by the coupling scenarios and improve the computation efficiency, a modified Benders decomposition algorithm is used to solve the model. The computational results show the following: (1) When wind power uncertainty is considered, generation companies prefer higher bidding quantities since the loss of wind power curtailment is much higher than the cost of additional power purchases in the current policy environment. (2) The wind power volatility has a strong negative effect on generation companies. The higher the power volatility is, the lower the profits, the bidding quantities, and the wind power curtailment of generation companies are. (3) The thermal power units play an important role in dealing with the wind power uncertainty in the strategic bidding problem, by shaving peak and filling valley probabilistic scheduling.