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AbstractContext The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use.Objective The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases.Methods We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence.Results Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment.Conclusions Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Abstract Background Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors is the primary cause of death among patients. Identifying novel and effective biomarkers is essential for understanding the mechanisms of metastasis in PCa patients and developing successful interventions. Methods Using the GSE8511 and GSE27616 data sets, 21 metastasis-related genes were identified through the weighted gene co-expression network analysis (WGCNA) method. Subsequent functional analysis of these genes was conducted on the gene set cancer analysis (GSCA) website. Cluster analysis was utilized to explore the relationship between these genes, immune infiltration in PCa, and the efficacy of targeted drug IC50 scores. Machine learning algorithms were then employed to construct diagnostic and prognostic models, assessing their predictive accuracy. Additionally, multivariate COX regression analysis highlighted the significant role of POLD1 and examined its association with DNA methylation. Finally, molecular docking and immunohistochemistry experiments were carried out to assess the binding affinity of POLD1 to PCa drugs and its impact on PCa prognosis. Results The study identified 21 metastasis-related genes using the WGCNA method, which were found to be associated with DNA damage, hormone AR activation, and inhibition of the RTK pathway. Cluster analysis confirmed a significant correlation between these genes and PCa metastasis, particularly in the context of immunotherapy and targeted therapy drugs. A diagnostic model combining multiple machine learning algorithms showed strong predictive capabilities for PCa diagnosis, while a transfer model using the LASSO algorithm also yielded promising results. POLD1 emerged as a key prognostic gene among the metastatic genes, showing associations with DNA methylation. Molecular docking experiments supported its high affinity with PCa-targeted drugs. Immunohistochemistry experiments further validated that increased POLD1 expression is linked to poor prognosis in PCa patients. Conclusions The developed diagnostic and metastasis models provide substantial value for patients with prostate cancer. The discovery of POLD1 as a novel biomarker related to prostate cancer metastasis offers a promising avenue for enhancing treatment of prostate cancer metastasis.

Introduction With the wide development of acupuncture clinical practice, acupuncture research has been conducted worldwide, of which the most common method is quantitative study. However, research questions around acupuncture cannot always be addressed by quantitative studies due to their intrinsic characteristics. Qualitative studies can perfectly complement this knowledge gap in acupuncture research. To date, few qualitative studies on acupuncture research have been summarised. The objective of this scoping review is to review the application status of qualitative studies in the field of acupuncture research.Methods In accordance with the framework put forward by Arksey and O'Malley, this proposed scoping review (registration DOI: https://doi.org/10.17605/OSF.IO/VYBMT) will be applied as the following steps: (1) identifying the research questions, (2) identifying relevant studies, (3) study selection, (4) charting the data and (5) collating, summarising and reporting the results. Six databases with Google Scholar and Baidu Scholar will be searched with a comprehensive searching strategy, and two reviewers finishing uniform training and pilot test will independently screen the potential literature to include eligible ones. Endnote 20 will be used to manage the literature; a predesigned, standardised Excel sheet will be used to load all information extracted. Findings of this scoping review will be reported and described in a narrative manner. Tables, charts or figures will be used to present the results and qualitative content analysis and thematic analysis based on grounded theory will be adopted to analyse the data. We initiated our search on 13 March 2024.Ethics and dissemination As scoping reviews are a form of secondary data analysis, ethical review is not required. Our research results will provide future research direction for qualitative studies of acupuncture and be disseminated through a peer-reviewed publication and related scientific conferences.

Objective: To compare the effects of electroacupuncture (EA) and moxibustion at Zusanli (ST 36) on the lung phenotype of rat offspring exposed to nicotine during the perinatal period. Methods: Pregnant Sprague-Dawley rats were randomly divided into 4 groups: the control group (saline only), the model group (nicotine only), the EA group (nicotine + EA at ST 36 acupoints bilaterally), and the moxibustion group (nicotine + moxibustion at ST 36 acupoints bilaterally). n = 6 rats per group. On postnatal day 21, the body weight, lung weight, and pulmonary function were determined and lung morphometry was performed. Peroxisome proliferator-activated receptor gamma and β-catenin levels in the lung tissue of offspring were also determined. Results: Perinatal nicotine exposure (PNE) results in decreased body and lung weights of offspring rats, abnormal lung tissue morphology, and significantly altered pulmonary function, showing an increase in total airway resistance and a decrease in tidal volume, minute ventilation, total airway compliance, and peak expiratory flow. Bilateral EA at ST 36 acupoints could block all of these perinatal nicotine-induced effects. Although moxibustion also had protective effects in nicotine-induced offspring lungs, some of these effects did not reach statistical significance, e.g., protection against the upregulation of β-catenin, the downregulation of PPARγ signaling, and the increase in peak expiratory flow. Conclusion: Maternal EA at ST 36 blocked the PNE-induced changes in key developmental signaling pathways, prevented the PNE-induced changes in lung morphology, and protected pulmonary function. Moxibustion at ST 36 showed similar but weaker protective effects against the PNE-induced changes in the exposed offspring. It is important to note that the mechanism underlying the protective effects of moxibustion at ST 36 may be different from those of EA at ST 36, and further research is needed to understand these differences.

To identify novel biomarkers for predicting prognosis and immune function in bladder cancer (BC) patients, we combined weighted correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis by using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and finally screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial–mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-cadherin, matrix metallopeptidase 2 (MMP2) and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+ T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating EMT process.

Objective: Many factors during pregnancy can induce intrauterine growth restriction (IUGR), resulting in various adverse perinatal outcomes such as low birth weight and multiple organ disorders. Among these factors, prenatal smoke/nicotine exposure is a common cause of IUGR, often associated with altered fetal lung development. The classical Wnt signaling pathway plays a vital role in lung development, and its alterations are commonly associated with developmental lung pathologies. The purpose of this study was to determine whether electroacupuncture (EA) at ''Zusanli'' (ST 36) points protects perinatal nicotine exposure (PNE)-induced offspring lung dysplasia through Wnt/β-catenin signaling pathway and to identify specific Wnt signaling pathway targets of EA. Methods: Following a well-established protocol, nicotine (1 mg/kg/ body weight) was administered subcutaneously to pregnant Sprague Dawley rat dams from gestational day 6 to postnatal day 21. In the EA group, dams were treated with EA at both ST 36 acupoints, while in another experimental group, Wnt/β-catenin signaling pathway agonist was injected subcutaneously (2 mg/kg/ body weight). Offspring body weight (PND 1, 7, 14, and 21), lung weight, Wnt signaling markers, pulmonary function, and lung morphology were determined at sacrifice on PND 21. Specifically, Western blotting and Real-time PCR were used to detect the protein and mRNA levels of critical Wnt signaling markers Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the offspring lung. The protein levels of β-catenin in lung tissue of offspring rats were detected by ELISA that of LEF-1 by Western blotting. Results: Compared to the control group, the body and lung weights of the offspring rats were significantly decreased in the nicotine-only exposed group. The pulmonary function determined as FVC, PEF, TV, and Cdyn was also significantly decreased, while PIF was significantly increased. The protein levels and mRNA expression of Wnt2, Wnt7b, FZD4, FZD7, LRP5, and LRP6 in the lung tissue of the PNE offspring rats were significantly increased. With EA administration at ST 36 acupoints concomitant with nicotine administration, the body and lung weights, pulmonary function (FVC, PEF, PIF, TV, and Cdyn), protein and mRNA levels Wnt signaling pathway markers (Wnt2, Wnt7b, FZD4, FZD7, LRP5, LRP6, β-catenin, and LEF-1) normalized and were not different from the control group. Notably, Wnt agonists agonist administration blocked the protective effects of EA against PNE-induced lung morphological, molecular, and function changes, highlighting the central significance of Wnt pathway signaling in PNE-induced offspring pulmonary pathology and its modulation by EA at ST 36 acupoints. Conclusion: Concomitant maternal EA at ST 36 acupoints from gestational day 6 to PND 21 protects against offspring PNE-induced lung phenotype. The protective effect is achieved by regulating the expression of Wnt ligand proteins (Wnt2 and Wnt7b) and receptor proteins (FZD4, FZD7, LRP5, and LRP6) upstream of the Wnt/β-catenin signaling pathway intermediates β-catenin, and LEF-1.

BackgroundPre-mRNA processing factor 19 (PRPF19) is an E3 ligase that plays a crucial role in repairing tumor-damaged cells and promoting cell survival. However, the predictive value and biological function of PRPF19 in bladder urothelial carcinoma (BLCA) require further investigation.MethodsIn this study, we utilized transcriptomic data and bladder cancer tissue microarrays to identify the high expression of PRPF19 in BLCA, suggesting its potential as a prognostic biomarker. To gain a better understanding of the role of PRPF19 in the immune microenvironment of BLCA, we performed single cell analysis and employed the LASSO method. Additionally, we examined the methylation profiles of PRPF19 using the SMART website. Our investigation confirmed the correlation between PRPF19 and BLCA cell senescence and stemness. Furthermore, we constructed a PRPF19-miR-125a-5p-LINC02693-MIR4435-2HG ceRNA network using the ENCORI and miRWALK databases.ResultsOur comprehensive analysis reveals that PRPF19 can serve as a prognostic marker for BLCA and is significantly associated with various immune-infiltrating cells in BLCA. Moreover, our findings suggest that PRPF19 influences cellular senescence through the regulation of stemness. Finally, we developed a ceRNA network that has the potential to predict the prognosis of BLCA patients.ConclusionWe confirmed the prognostic value and multiple biological functions of PRPF19 in BLCA. Furthermore, the specific ceRNA network can be used as a potential therapeutic target for BLCA.

Astragalus melilotoides Pall. 1776 is a perennial leguminous forage, widely distributed in northern China, with cold, drought and disease resistance characteristics. Here, we determined the complete chloroplast (cp) genome sequence of A. melilotoides. It was 123,827 bp in length and 36.97% GC content with IR loss. The cp genome contained 110 complete genes, including 76 protein-coding genes, 30 tRNA genes, and four rRNA genes. A maximum likelihood (ML) phylogenetic tree revealed that A. melilotoides was related to A. americanus, A. gummifer, A. mongholicus, A. nakaianus, A. mongholicus var. nakaianus, and A. membranaceus var. membranaceus. The cp genome analysis of A. melilotoides will provide a reference for the phylogenetic study of Astragalus in the future.

Stipa bungeana Trin. 1833 is an important forage grass in Poaceae, widely distributed in the temperate steppe of Northern China, with strong grazing tolerance and feeding value. In this study, we performed the complete chloroplast (cp) genome sequence of S. bungeana to explore its phylogenetic position with other Stipa. The results showed that the circular complete cp genome of S. bungeana was 137,759 bp in length, including a large single copy (LSC) of 81,652 bp, a small single copy (SSC) of 12,817 bp, and two inverted repeats (IR) of 21,645 bp. The GC content accounts for 43.71% and annotated 134 single genes, which include 87 protein-coding genes, eight rRNA genes, and 39 tRNA genes. Maximum-likelihood (ML) phylogenetic tree suggested that the S. bungeana was closely related to other Stipa except for S. purpurea.

Abstract The temporal stability of grassland plant communities is substantially affected by soil nutrient enrichment. However, the potential main and interactive effects of arbuscular mycorrhizal fungi (AMF) and soil nitrogen (N) and phosphorus (P) enrichment on the stability of plant productivity have not yet been clarified. We combined a three‐year in situ field experiment to assess the impacts of soil fertilization and AMF on the stability of plant productivity. P addition decreased the stability of plant productivity by increasing the standard deviation relative to the mean of plant productivity. However, compared to species richness, the stability of C3 grasses and other functional groups asynchrony were the most important drivers changing the stability of plant productivity. The negative impacts of P addition overrode the impacts of AMF on the stability of plant productivity. Overall, our study suggests the importance of soil nutrient availability over AMF in terms of shaping the stability of plant productivity. Our results also suggest that three‐year anthropogenic soil nutrient enrichment could reduce the stability of plant communities in grassland regardless of AMF in the P‐limited grassland ecosystem.

Abstract Vincetoxicum mongolicum Maxim. (1876), is a perennial medicinal herb, widely distributed in the Loess Plateau of China. Here, we sequenced, assembled, and annotated the complete chloroplast (cp) genome of V. mongolicum, and compared the highly variable gene regions and phylogenetic positions between V. mongolicum and other related species. Results showed that the complete cp genome of V. mongolicum was 160,157 bp in length, containing a large single copy (LSC) region of 91,263 bp, a pair of inverted repeats (IR) region of 23,892 bp, and a small single copy (SSC) region of 21,110 bp. The GC content accounts for 37.8%, and we annotated 131 single genes, which include 86 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. By comparing and analyzing the variable region of the cp gene of V. mongolicum and other Vincetoxicum, we found that the variable sequences of rpoC1-rpoB, ycf4-cemA, ndhF, ndhF-rpl32, and rpl32-ccsA fragments were highly significant, which could be targeted as the DNA barcodes for evidence of V. mongolicum and its relatives in Apocynaceae. Maximum-likelihood (ML) phylogenetic tree analysis elucidated that V. mongolicum was sister to V. pycnostelma with strong support. Our results provide useful information for future phylogenetic studies and plastid super-barcodes of the family Apocynaceae.

Cadmium-contaminated soil significantly threatens global food security and human health. This scenario gives rise to significant worries regarding widespread environmental pollution. Biochar and arbuscular mycorrhizal fungi (AMF) can effectively immobilize cadmium in the soil in an environmentally friendly way. Existing studies have separately focused on the feasibility of each in remediating polluted soil. However, their association during the remediation of cadmium-polluted soils remains unclear. This review paper aims to elucidate the potential of biochar, in conjunction with AMF, as a strategy to remediate soil contaminated with cadmium. This paper comprehensively analyzes the current understanding of the processes in cadmium immobilization in the soil environment by examining the synergistic interactions between biochar and AMF. Key factors influencing the efficacy of this approach, such as biochar properties, AMF species, and soil conditions, are discussed. The influences of biochar–AMF interactions on plant growth, nutrient uptake, and overall ecosystem health in cadmium-contaminated environments are highlighted. This review indicates that combining biochar and AMF can improve cadmium immobilization. The presence of AMF in the soil can create numerous binding sites on biochar for cadmium ions, effectively immobilizing them in the soil. Insights from this review contribute to a deeper understanding of sustainable and eco-friendly approaches to remediate cadmium-contaminated soils, offering potential applications in agriculture and environmental management.

Abstract Following the COVID-19 outbreak, psychological stress was particularly pronounced in the student population due to prolonged home isolation, online study, closed management, graduation, and employment pressures. The objective of this study is to identify the incidence of psychological stress reactions in student populations following a global outbreak and the associated influencing factors. Four English databases (Pubmed, Embase, Cochrane Library, Web of Science) and four Chinese biomedical databases (Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, Wanfang) were searched in this study. We also retrieved other search engines manually. The search period was from the time of database creation to 10 March 2022. This study included cross-sectional studies related to psychological stress reactions in student populations during the COVID-19 epidemic. Three groups of researchers screened the retrieved studies and assessed the quality of the included studies using the Agency for Healthcare Research and Quality Cross-Sectional Study Quality Assessment Checklist. A random-effects model was used to analyze the prevalence of depression, anxiety, stress, and fear symptoms in the student population during the COVID-19 epidemic. Of the 146,330 records retrieved, we included 104 studies (n = 2,088,032). The quality of included studies was moderate. The prevalence of depressive symptoms in the student population during the epidemic was 32.0% (95% CI [28.0–37.0%]); anxiety symptoms was 28.0% (95% CI [24.0–32.0%]); stress symptoms was 31.0% (95% CI [23.0–39.0%]); and fear symptoms was 33.0% (95% CI [20.0–49.0%]). The prevalence differed by gender, epidemic stage, region, education stage, student major and assessment tool. The prevalence of psychological stress in the student population during the COVID-19 epidemic may be higher compared to the global prevalence of psychological stress. We need to alleviate psychological stress in the student population in a targeted manner to provide mental health services to safeguard the student population.

IntroductionExtended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin–tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs.MethodsA monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae.ResultsOf the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01).DiscussionIn terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

BackgroundSeveral randomized controlled trials (RCTs) have confirmed the favorable clinical benefit of pembrolizumab in advanced non-small cell lung cancer (NSCLC). However, considering the strict inclusion and exclusion criteria in clinical research, there are certain differences between patients in the real-world, it is unclear whether the findings of clinical trials are fully representative of the treatment efficacy in patients who will eventually use it. Therefore, to further comprehensively assess the efficacy and safety of pembrolizumab in NSCLC, we conducted a systematic review and meta-analysis based on the latest RCTs and real-world studies (RWSs).MethodsWe systematically searched PubMed, Embase, The Cochrane Library, The Web of Science, and clinical trials.gov as of December 2021. RCTs and RWSs of patients receiving pembrolizumab monotherapy or in combination with chemotherapy for advanced NSCLC were included.ResultsThe meta-analysis ultimately included 11 RCTs and 26 RWSs with a total of 10,695 patients. The primary outcomes of this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), serious adverse events (SAEs), the incidence of severe pneumonia reactions, and drug-related mortality. Direct meta-analysis results showed that in RCTs, pembrolizumab in combination with chemotherapy was superior to chemotherapy in terms of OS (HR=0.60, 95%CI:0.50-0.73), PFS (HR=0.47, 95%CI:0.38-0.58) and ORR (OR=3.22, 95%CI:2.57-4.03); pembrolizumab monotherapy was superior to chemotherapy in terms of OS (HR=0.73, 95%CI:0.66-0.80) and ORR (OR=1.90, 95%CI:1.17-3.09), but comparable to chemotherapy in terms of PFS (HR=0.83, 95%CI:0.66-1.04). The ORR values in retrospective single-arm studies were 45% (40%-51%).ConclusionIn RCTs, pembrolizumab monotherapy or in combination with chemotherapy is more effective and safer than chemotherapy for advanced NSCLC. In RWSs, ECOG PS 0-1 was shown to correlate with PFS and OS for patients with NSCLC.

Green-color sandstone illustrates close association to the deposition of sandstone-type uranium via field exploration, which is similar to the Dongsheng area. Geochemical research on acidolysis hydrocarbon, Th/U, Fe3+/Fe2+ and organic carbon content in Zhiluo Formation were conducted, aiming to decipher the uranium mineralization in the green color sandstone.The result shows that: (1) Primary gray sandstone hold the higher content of hydrocarbon than the green altered and oxidized ones, and then the green altered sandstone.(2)Both oxidized sandstone and green alteration sandstone were chartererised by high Th/U (0.37-1.82) and low organic content (0.01%-1.24%).Green alteration was probably triggered by intensive reduced material, that is, the secondary reduction of reducing fluid.The early interlayer oxidation provided the material basis for uranium mineralization, and the later secondary reduction preserved the integrity of the ore body.This study has an important indication for the discrimination and division of interlayer oxidation zone in this area, and provides an important basis for the study of metallogenic regularity of sandstone type uranium deposits.

BackgroundNeoadjuvant anti-programmed death receptor-1 (PD-1) blockade has been reported to improve the prognosis of locally advanced esophageal squamous cell carcinoma (ESCC). This study was aimed to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemoradiotherapy in locally advanced ESCC.MethodsWe retrospectively enrolled ESCC patients who received camrelizumab plus chemoradiotherapy as neoadjuvant therapy before surgery from May 2019 to September 2021.ResultsA total of 38 eligible patients were enrolled. The neoadjuvant treatment was well tolerated with no serious treatment-related adverse events. 36 (94.7%) patients achieved a R0 resection without hospital mortality or any other serious intraoperative complications. The objective response rate (ORR) was 63.2% and the disease control rate (DCR) was 100.0%. The major pathological response (MPR) was 50.0% and the complete pathological response (pCR) was 39.5%. With a median follow-up of 18.5 months, 6 (15.8%) patients had died. The overall survival (OS) and disease-free survival (DFS) at 12 months were 87.6% and 78.7%, respectively. Subgroup analysis demonstrated that patients who got MPR or pCR achieved improved survival, while PD-L1 expression did not reach statistically difference in predicting survival.ConclusionsNeoadjuvant camrelizumab plus chemoradiotherapy is safe and efficacious in treating patients with locally advanced ESCC.

Abstract Background Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost‐effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD‐L1) test on the cost‐effectiveness is also unknown. The current study assessed the cost‐effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers’ perspective. Materials and Methods A literature‐based Markov model was conducted using KEYNOTE‐189 trial data to compare cost and quality‐adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro‐chemotherapy combination and chemotherapy strategy without PD‐L1 test, and treatment strategy according to their PD‐L1 status. Results In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD‐L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD‐L1 test strategy. In the PD‐L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD‐L1 test strategy. Lowering Pembro price can also partly decrease the ICERs. Conclusion Compared with chemotherapy, the combination strategy is not cost‐effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD‐L1 test for patient selection and price reduction could improve the cost‐effective probabilities of immunotherapy for nonsquamous NSCLC.

Data are an important parts of building applications and providing services to users. With the development of modern technology, the requirements for data quantity, quality, and processing capabilities have become more stringent. Sufficient high-quality data are the foundation for most mobile applications. It is important to collect enough data to effectively build your application. In addition to ensure the amount of data collected, the quality of the data collected is also important. Otherwise, a large amount of data redundancy will occur, which will cause trouble for data processing. At the same time, large amounts of data also mean the need for data processing capabilities. Traditional processing methods cannot meet the growing demand for data processing. Mobile computing is a promising solution to meet the growing computing needs of various mobile applications. The advancement and application of mobile computing require more intelligent ways to sense and collect data, which constantly poses new challenges to researchers.

Objective: To develop and validate a scoring system to predict the risk of in-hospital death in patients with intra-abdominal infection (IAI).Materials and Methods: Patients with IAI (n = 417) treated at our hospital between June 2010 and May 2020 were retrospectively reviewed. Risk factors for in-hospital death were identified by logistic regression analysis. The regression coefficients of each risk factor were re-assigned using the mathematical transformation principle to establish a convenient predictive scoring system. The scoring system was internally validated by bootstrapping sample method.Results: Fifty-three (53/417, 12.7%) patients died during hospitalization. On logistic regression analysis, high APACHE II score (P = 0.012), pneumonia (P = 0.002), abdominal surgery (P = 0.001), hypoproteinemia (P = 0.025), and chronic renal insufficiency (P = 0.001) were independent risk factors for in-hospital death. On receiver operating characteristic curve analysis, the composite index combining these five risk factors showed a 62.3% sensitivity and 80.2% specificity for predicting in-hospital death (area under the curve: 0.778; 95% confidence interval: 0.711–0.845, P < 0.001). The predictive ability of the composite index was better than that of each independent risk factor. A scoring system (0–14 points) was established by re-assigning each risk factor based on the logistic regression coefficient: APACHE II score (10–15 score, 1 point; >15 score, 4 points); pneumonia (2 points), abdominal surgery (2 points), hypoproteinemia (2 points), and chronic renal insufficiency (4 points). Internal validation by 1,000 bootstrapping sample showed relatively high discriminative ability of the scoring system (C-index = 0.756, 95% confidence interval: 0.753–0.758).Conclusions: The predictive scoring system based on APACHE II score, pneumonia, abdominal surgery, hypoproteinemia, and chronic renal insufficiency can help predict the risk of in-hospital death in patients with IAI.

A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a Ki of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC50 values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation.

Three new helvolic acid derivatives (named sarocladilactone A (1), sarocladilactone B (2) and sarocladic acid A (3a)), together with five known compounds (6,16-diacetoxy-25-hy- droxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (3b), helvolic acid (4), helvolinic acid (5), 6-desacetoxy-helvolic acid (6) and 1,2-dihydrohelvolic acid (7)), were isolated from the endophytic fungus DX-THL3, obtained from the leaf of Dongxiang wild rice (Oryza rufipogon Griff.). The structures of the new compounds were elucidated via HR-MS, extensive 1D and 2D NMR analysis and comparison with reported data. Compounds 1, 2, 4, 5, 6 and 7 exhibited potent antibacterial activities. In particular, sarocladilactone B (2), helvolinic acid (5) and 6-desacetoxy-helvolic acid (6) exhibited strongly Staphylococcus aureus inhibitory activity with minimum inhibitory concentration (MIC) values of 4, 1 and 4 μg/mL, respectively. The structure–activity relationship (SAR) of these compounds was primarily summarized.

Liposarcoma is an often fatal cancer of fat cells. Mechanisms of liposarcoma development are incompletely understood. The cleavage of fatty acids from acylglycerols (lipolysis) has been implicated in cancer. We generated mice with adipose tissue deficiency of two major enzymes of lipolysis, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), encoded respectively by Pnpla2 and Lipe. Adipocytes from double adipose knockout (DAKO) mice, deficient in both ATGL and HSL, showed near-complete deficiency of lipolysis. All DAKO mice developed liposarcoma between 11 and 14 months of age. No tumors occurred in single knockout or control mice. The transcriptome of DAKO adipose tissue showed marked differences from single knockout and normal controls as early as 3 months. Gpnmb and G0s2 were among the most highly dysregulated genes in premalignant and malignant DAKO adipose tissue, suggesting a potential utility as early markers of the disease. Similar changes of GPNMB and G0S2 expression were present in a human liposarcoma database. These results show that a previously-unknown, fully penetrant epistatic interaction between Pnpla2 and Lipe can cause liposarcoma in mice. DAKO mice provide a promising model for studying early premalignant changes that lead to late-onset malignant disease.

Objective: To evaluate the lipid-regulating effect of crude-herb moxibustion on rats with dyslipidemia. Methods: Fifty-four Sprague–Dawley rats were randomly divided into six groups with nine rats each. Control group rats were fed a normal diet, and bilateral acu-point Fenglong (equivalent to ST40 in humans) on the hind legs were covered with a placebo (general mucilage) for 2 hours each day. Model group rats were fed a high-lipid diet for 2 weeks. Therapy group rats were fed a high-lipid diet for 2 weeks and then administered crude-herb moxibustion at ST40 for 2 hours each day for the next 2 weeks. Prevention group rats were administered crude-herb moxibustion 2 hours a day for 2 weeks and then fed a high-lipid diet for the subsequent 2 weeks. Prevention/Therapy group rats were each administered crude-herb moxibustion at ST40 for 2 hours each day for 2 weeks, followed by a high-lipid diet for the next 2 weeks, and then crude-herb moxibustion again at ST40 for another 2 weeks. Simvastatin group rats were fed a high-lipid diet for 2 weeks and then treated with simvastatin for the next 2 weeks. Blood lipids, hepatosomatic indices (HSIs) and epididymal fat pad weights of all rats were examined. Results: Compared with the Model group, levels of total cholesterol (TC), glycerinate, low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) in plasma collected from the Therapy group, the Prevention/Therapy group, and the Simvastatin group were decreased. Moreover, compared with the Model group, HSIs in Therapy group rats were also decreased following administration of crude-herb moxibustion, but TC, TG, HDL-C, LDL-C, and VLDL-C levels in the Prevention group were higher than those in the Model group. Conclusion: The results reveal that blood lipids and HSIs appear to be modulated by the effect of crude-herb moxibustion and suggest therapeutic strategies for the treatment of dyslipidemia.

In this study, angiotensin-I converting enzyme (ACE) inhibitory tripeptides from rice protein hydrolysate were purified and their properties were further characterized. Val-Asn-Pro (VNP) and Val-Trp-Pro (VWP) were successfully purified from rice protein hydrolysate through multi-step isolation and purification comprising of ultrafiltration and DA201-C macroporous adsorption resin, followed by a two-step reverse phase high performance liquid chromatography (RP-HPLC). The sequences of tripeptides were separately assayed by using automated protein/peptide sequencer. In addition, the stability of the tripeptides against ACE and simulated gastrointestinal proteases, ACE-inhibitory kinetics, and their antihypertensive effects in vivo were evaluated. Our results showed that VNP (IC50 value of 6.4 μM) and VWP (IC50 value of 4.5 μM) were both competitive ACE inhibitors, and stability against ACE and gastrointestinal proteases of pepsin and chymotrypsin. Furthermore, single oral administration of the tripeptides VNP and VWP at 5 mg/kg body weight in spontaneously hypertensive rats (SHRs) significantly decreased the systolic blood pressure (SBP) of 29 and 38 mmHg (P

Antibiotic abuse can lead to antibiotic resistance, which is a severe problem in China. The purpose of this study is to evaluate the short-term effects of antimicrobial stewardship strategies, including formulary restriction, preauthorization, perioperative quinolone restriction, and control of total antibiotic consumption in the ICU at a tertiary hospital in China. After implementation of antimicrobial stewardship, the total antibiotic consumption in the ICU significantly decreased. The defined daily doses (DDDs) per 100 patient-days decreased from 197.65 to 143.41; however, the consumption of cephalosporins increased from 53.65 to 63.17 DDDs. Significant improvements in resistance to amikacin, gentamicin, ciprofloxacin, ofloxacin, ceftriaxone, ceftazidime, and piperacillin in Enterobacteriaceae and resistance to ceftazidime, imipenem, and meropenem in non-fermenting Gram-negative rods were observed. In addition, the initial use of no antibiotics or of a single antibiotic significantly increased (P