Cu-Catalyzed Regioselective Silylation of Chloro-Substituted Allenyl-Bdan.

A copper-catalyzed efficient regioselective silylation reaction of chloro-substituted allenyl-Bdan was developed. Under mild reaction conditions, allenyl and propargyl silane compounds can be selectively obtained in moderate to high yields by adjusting the bases and solvents used in the reactions. This study offers direct and efficient methods for synthesizing multifunctionalized allenyl and propargyl silane compounds from the same initial material of chloro-substituted allenyl-Bdan.

SUMF1 overexpression promotes tumorous cell growth and migration and is correlated with the immune status of patients with glioma.

BACKGROUND: Glioma is a prevalent type of malignant tumor. To date, there is a lack of literature reports that have examined the association between sulfatase modifying factor 1 (SUMF1) and glioma. METHODS: The levels of SUMF1 were examined, and their relationships with the diagnosis, prognosis, and immune microenvironment of patients with glioma were investigated. Cox and Lasso regression analysis were employed to construct nomograms and risk models associated with SUMF1. The functions and mechanisms of SUMF1 were explored and verified using gene ontology, cell counting kit-8, wound healing, western blotting, and transwell experiments. RESULTS: SUMF1 expression tended to increase in glioma tissues. SUMF1 overexpression was linked to the diagnosis of cancer, survival events, isocitrate dehydrogenase status, age, and histological subtype and was positively correlated with poor prognosis in patients with glioma. SUMF1 overexpression was an independent risk factor for poor prognosis. SUMF1-related nomograms and high-risk scores could predict the outcome of patients with glioma. SUMF1 co-expressed genes were involved in cytokine, T-cell activation, and lymphocyte proliferation. Inhibiting the expression of SUMF1 could deter the proliferation, migration, and invasion of glioma cells through epithelial mesenchymal transition. SUMF1 overexpression was significantly associated with the stromal score, immune cells (such as macrophages, neutrophils, activated dendritic cells), estimate score, immune score, and the expression of the programmed cell death 1, cytotoxic T-lymphocyte associated protein 4, CD79A and other immune cell marker. CONCLUSION: SUMF1 overexpression was found to be correlated with adverse prognosis, cancer detection, and immune status in patients with glioma. Inhibiting the expression of SUMF1 was observed to deter the proliferation, migration, and invasion of cancer cells. The nomograms and risk models associated with SUMF1 could predict the prognosis of patients with glioma.

Assembly of Homochiral Aluminum Oxo Clusters for Circularly Polarized Luminescence.

Chiral aluminum oxo clusters (cAlOCs) are distinguished from other classes of materials on account of their abundance in the earth's crust and their potential for sustainable development. However, the practical synthesis of cAlOCs is rarely known. Herein, we adopt a synergistic coordination strategy by using chiral amino acid ligands as bridges and auxiliary pyridine-2,6-dicarboxylic acid as chelating ligands and successfully isolate an extensive family of cAlOCs. They integrate molecular chirality, absolute helicity, and intrinsic hydrogen-bonded chiral topology. Moreover, they have the structural characteristics of one-dimensional channels and replaceable counteranions, which make them well combined with fluorescent dyes for circularly polarized luminescence (CPL). The absolute luminescence dissymmetry factor (glum) of up to the 10-3 order is comparable to several noble metals, revealing the enormous potential of cAlOCs in low-cost chiral materials. We hope this work will inspire new discoveries in the field of chirality and provide new opportunities for constructing low-cost chiral materials.

Three novel species of the genus Flavobacterium, Flavobacterium odoriferum sp. nov., Flavobacterium fragile sp. nov. and Flavobacterium luminosum sp. nov., isolated from activated sludge.

Three Gram-stain-negative, rod-shaped, non-spore-forming bacteria were isolated from activated sludge samples. The results of phylogenetic analysis based on the 16S rRNA gene sequences indicated that the three strains, designated HXWNR29T, HXWNR69T and HXWNR70T, had the highest sequence similarity to the type strains Flavobacterium cheniae NJ-26T, Flavobacterium channae KSM-R2A30T and Flavobacterium amniphilum KYPY10T with similarities of 97.66 %, 98.66 and 98.14 %, respectively. The draft genomes of these three strains were 2.93 Mbp (HXWNR29T), 2.69 Mbp (HXWNR69T) and 2.65 Mbp (HXWNR70T) long with DNA G+C contents of 31.84 %, 32.83 % and 34.66 %, respectively. These genomes contained many genes responsible for carbohydrate degradation and antibiotic resistance. The major fatty acids (>5 %) included iso-C15 : 0, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. The major menaquinone was MK-6 for all the three strains. The average nucleotide identity (ANI; 72.7-88.5 %) and digital DNA-DNA hybridization (dDDH; 19.6-35.3 %) results further indicated that these three strains represented three novel species within the genus Flavobacterium, for which the names Flavobacterium odoriferum sp. nov. (type strain HXWNR29T = KCTC 92446T = CGMCC 1.61821T), Flavobacterium fragile sp. nov. (type strain HXWNR69T = KCTC 92468T = CGMCC 1.61442T) and Flavobacterium luminosum sp. nov. (type strain HXWNR70T = KCTC 92447T = CGMCC 1.61443T) are proposed.

Therapeutic mechanisms of ginseng in coronary heart disease.

Coronary heart disease (CHD) is the most common clinical manifestation of cardiovascular disease. It is characterized by myocardial ischemia, which is caused by coronary atherosclerosis. CHD is a significant global health problem with increasing prevalence every year because of significant changes in the lifestyles and diets. Ginseng is a traditional Chinese medicinal herb that has been used in food preparations and traditional medicine for several centuries. Several studies have demonstrated that ginseng improved cardiac function by normalizing blood glucose levels and decreasing blood pressure, oxidative stress, platelet aggregation, and lipid dysregulation in vivo. This review describes the current understanding of the mechanisms by which ginseng alleviates CHD, and provides a reference for the clinical development and application of ginseng as an alternative therapy for CHD.

Clinical features and therapeutic management of choroidal osteoma: A systematic review.

Choroidal osteoma is a benign ossifying tumor within the choroid. Complications associated with choroidal osteoma, including disruption of retinal pigment epithelium, atrophy of photoreceptors, subretinal fluid, and choroidal neovascularization, present challenges for clinicians, and management remain controversial. We performed a comprehensive search in the PubMed, EMBASE, and Ovid databases for published studies and case reports relating to the management of choroidal osteoma. Since it was first described in 1978, various case reports of ocular complications associated with choroidal osteoma have been documented, and various therapies have yielded different outcomes. We systematically evaluate the literature published on this rare entity.

DLGNet: A dual-branch lesion-aware network with the supervised Gaussian Mixture model for colon lesions classification in colonoscopy images.

Colorectal cancer is one of the malignant tumors with the highest mortality due to the lack of obvious early symptoms. It is usually in the advanced stage when it is discovered. Thus the automatic and accurate classification of early colon lesions is of great significance for clinically estimating the status of colon lesions and formulating appropriate diagnostic programs. However, it is challenging to classify full-stage colon lesions due to the large inter-class similarities and intra-class differences of the images. In this work, we propose a novel dual-branch lesion-aware neural network (DLGNet) to classify intestinal lesions by exploring the intrinsic relationship between diseases, composed of four modules: lesion location module, dual-branch classification module, attention guidance module, and inter-class Gaussian loss function. Specifically, the elaborate dual-branch module integrates the original image and the lesion patch obtained by the lesion localization module to explore and interact with lesion-specific features from a global and local perspective. Also, the feature-guided module guides the model to pay attention to the disease-specific features by learning remote dependencies through spatial and channel attention after network feature learning. Finally, the inter-class Gaussian loss function is proposed, which assumes that each feature extracted by the network is an independent Gaussian distribution, and the inter-class clustering is more compact, thereby improving the discriminative ability of the network. The extensive experiments on the collected 2568 colonoscopy images have an average accuracy of 91.50%, and the proposed method surpasses the state-of-the-art methods. This study is the first time that colon lesions are classified at each stage and achieves promising colon disease classification performance. To motivate the community, we have made our code publicly available via https://github.com/soleilssss/DLGNet.

Automatic 3-D spine curve measurement in freehand ultrasound via structure-aware reinforcement learning spinous process localization.

Freehand 3-D ultrasound systems have been advanced in scoliosis assessment to avoid radiation hazards, especially for teenagers. This novel 3-D imaging method also makes it possible to evaluate the spine curvature automatically from the corresponding 3-D projection images. However, most approaches neglect the three-dimensional spine deformity by only using the rendering images, thus limiting their usage in clinical applications. In this study, we proposed a structure-aware localization model to directly identify the spinous processes for automatic 3-D spine curve measurement using the images acquired with freehand 3-D ultrasound imaging. The pivot is to leverage a novel reinforcement learning (RL) framework to localize the landmarks, which adopts a multi-scale agent to boost structure representation with positional information. We also introduced a structure similarity prediction mechanism to perceive the targets with apparent spinous process structures. Finally, a two-fold filtering strategy was proposed to screen the detected spinous processes landmarks iteratively, followed by a three-dimensional spine curve fitting for the spine curvature assessments. We evaluated the proposed model on 3-D ultrasound images among subjects with different scoliotic angles. The results showed that the mean localization accuracy of the proposed landmark localization algorithm was 5.95 pixels. Also, the curvature angles on the coronal plane obtained by the new method had a high linear correlation with those by manual measurement (R = 0.86, p < 0.001). These results demonstrated the potential of our proposed method for facilitating the 3-D assessment of scoliosis, especially for 3-D spine deformity assessment.

Insufficient Oligodendrocyte Turnover in Optic Nerve Contributes to Age-Related Axon Loss and Visual Deficits.

Age-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available up-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13-18 months) and old (20-22 months) mice of either sex compared with adult mice (3-8 months), accompanied by functional deficits. Oligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL turnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis displayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and visual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice. Genetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual function. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clemastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine treatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved visual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and visual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function.SIGNIFICANCE STATEMENT Oligodendrocyte (OL) turnover has been reported in adult optic nerves (ONs), but the longitudinal change and functional significance of OL turnover during aging remain largely unknown. Using cell-lineage tracing and oligodendroglia-specific manipulation, this study reported that OL generation was active in adult ONs and the efficiency decreased in an age-dependent manner. Genetically dampening OL generation by Olig2 ablation resulted in significant axon loss and retinal degeneration, along with delayed visual signal transmission. Conversely, pro-myelination approaches significantly increased new myelin generation in aging ONs, and consequently preserved retinal integrity and visual function. Our findings indicate that promoting OL generation might be a promising strategy to preserve visual function from age-related decline.

From an aluminum oxo cluster to an aluminum oxo cluster organic cage.

Presented herein is an example of the conversion of an aluminum oxo cluster (AlOC) to an aluminum oxo cluster organic cage (AlOCOC). We successfully synthesized the first example of an aluminum cluster-based organic cage-Al12 tetrahedral cage via an Al3 cluster. The use of 4-pyrazolecarboxylic acid plays an important role in the construction of the organic cage. Due to the presence of partially deprotonated ligands, the hydrogen-bonding interactions between the discrete tetrahedra generate porous supramolecular structures. Considering the high porosity and the abundant N-H sites, we further investigated the performance of the material towards iodine capture.

Potential health and economic impacts of shifting manufacturing from China to Indonesia or India.

The diversification or decoupling of production chains from China to alternative Asian countries such as India or Indonesia would impact the spatial distribution of anthropogenic emissions, with corresponding economic impacts due to mortality associated with particulate matter exposure. We evaluated these changes using the Community Earth System Model, the Integrated Exposure-Response (IER) model and Willingness To Pay (WTP) method. Significant effects on PM2.5 related mortality and economic cost for these deaths were seen in many East, Southeast and South Asian countries, particularly those immediately downwind of these three countries. Transferring all of export-related manufacturing to Indonesia resulted in significant mortality decreases in China and South Korea by 78k (5 per 100k) and 1k (2 per 100k) respectively, while Indonesia's mortality significantly increased (73.7k; 29 per 100k), as well as India, Pakistan and Nepal. When production was transferred to India, mortality rates in East Asia show similar changes to the Indonesian scenario, while mortalities in India increased dramatically (87.9k; 6 per 100k), and mortalities in many neighbors of India were also severely increased. Nevertheless, the economic costs for PM2.5 related mortality were much smaller than national GDP changes in China (0.9 % of GDP vs. 18.3 % of GDP), India (2.7 % of GDP vs. 84.3 % of GDP) or Indonesia (9.4 % of GDP vs. 337 % of GDP) due to shifting all of export-related production lines from China to India or Indonesia. Morally, part of the benefits of economic activity should be used to compensate the neighboring communities where mortality increases occur.

Pharmacoeconomic evaluation of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer / 中国药房

OBJECTIVE To evaluate the economics of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer （ES-SCLC） from the perspective of health system in China. METHODS A partitioned survival model was constructed based on the ASTRUM-005 clinical trial and related literature data， with a model simulation time frame of 10 years and a 3-week cycle， and both cost and utility values were discounted using a 5% discount rate. The quality-adjusted life year （QALY） was used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the economics of serplulimab combined with chemotherapy regimens （serplulimab group） versus chemotherapy alone regimens （chemotherapy alone group） for the first-line treatment of ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results of the base-case analysis and to conduct a scenario analysis for the serplulimab patient assistance program. RESULTS The results of the base-case analysis showed that compared with chemotherapy alone group， ICER of serplulimab group was 758 690.27 yuan/QALY， which was higher than 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold. The results of the scenario analysis showed that compared with chemotherapy alone group， the ICER of serplulimab group was 172 275.74 yuan/QALY， which was below above WTP threshold. The one-way sensitivity analysis showed that the progress-free survival utility value， serplulimab price and so on had a significant impact on the model results. The results of the probabilistic sensitivity analysis showed that the probability of the serplulimab group being economic was 0 when the serplulimab patient assistance program was not considered， but 100% when the patient assistance program was considered. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2022， the serplulimab group is no cost-effectiveness compared to the chemotherapy alone group； however， this result is reversed when the patient assistance program is taken into account.

Microvirga roseola sp. nov. and Microvirga lenta sp. nov., isolated from Taklamakan Desert soil.

Two Gram-negative, rod-shaped, non-spore-forming bacteria, designated SM9T and SM2T, were isolated from Taklamakan Desert soil samples. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strains SM9T and SM2T had the highest sequence similarity to the type strains Microvirga indica BCRC 80972T and Microvirga soli NBRC 112417T with similarity values of 98.2 and 97.7 %, respectively, and Microvirga was among the predominant genera in the desert soil. The draft genomes of these two strains were 4.56 Mbp (SM9T) and 5.08 Mbp (SM2T) long with 65.1 mol% (SM9T) and 63.5 mol% (SM2T) G+C content. To adapt to the desert environment, these two strains possessed pathways for the synthesis of stress metabolite trehalose. The major fatty acids (>5 %) included C18 : 1 ω9c in SM2T, but C16 : 0, C18 : 0 and C19 : 0 cyclo ω8c in SM9T, while the major menaquinone was ubiquinone 10 in both strains. The major polar lipids of SM9T and SM2T were phosphatidylglycerol, phosphatidylethanolamine and phospholipid. The average nucleotide identity and digital DNA-DNA hybridization results further indicated that strains SM9T and SM2T were distinguished from phylogenetically related species and represented two novel species within the genus Microvirga, for which the names Microvirga roseola sp. nov. (type strain SM2T=KCTC 72792T=CGMCC 1.17776T) and Microvirga lenta sp. nov. (type strain SM9T=KCTC 82729T=CCTCC AB 2021131T) are proposed.

Halalkalibacterium roseum gen. nov., sp. nov., a new member of the family Balneolaceae isolated from soil.

A Gram-stain-negative, non-motile, moderately halophilic and facultatively anaerobic bacterium, designated YR4-1T, was isolated from a saline-alkali and sorghum-planting soil sample collected in Dongying, Shandong Province, PR China. Growth occurred at 28-45 °C with the presence of 4.0-20.0 % (w/v) NaCl and pH 6.0-9.0. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that YR4-1T shared the highest similarity of 92.1-92.4 % with the valid published species of Aliifodinibius. The isolate formed a separate clade at the genus level in recently described family Balneolaceae. The draft genome of strain YR4-1T is 3.83 Mbp long with 44.0 mol% G+C content. The strain possesses several genes involved in the osmotic stress response mechanism and diverse metabolic pathways, probably for the living in saline environment. This may lead to a better understanding of the underrepresented Balneolaceae lineage. The major menaquinone was MK-7. The main polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipids, aminophosphoglycolipid, one glycolipid, and four unidentified lipids. The predominant cellular fatty acids were iso-C15 : 0 (35.7 %) and anteiso-C15 : 0 (33.5 %). On the basis of its phenotypic, chemotaxonomic and phylogenetic features, strain YR4-1T represents a novel species of a new genus, for which the name Halalkalibacterium roseum gen. nov., sp. nov. is proposed. The type strain is YR4-1T (=CGMCC 1.17777T=KCTC 72795T).

Cost-utility analysis of durvalumab for consolidation therapy after chemoradiotherapy for stage Ⅲ non-small cell lung cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.

Cost-utility analysis of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis ，and to provide reference for relevant decision-making. METHODS From the perspective of Chinese health system ，Excel 2003 software was used to establish Markov model ，and cost-utility analysis was used to evaluate the cost-effectiveness of denosumab or zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis. Pharmacotherapy effects were obtained from the network Meta-analysis ，and cost and health-utility value data were obtained from the published literature or network ，etc. The model cycle was 1 year，and the simulation time limit was the patient ’s lifetime. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the impact of model parameter changes on the robustness of the results ；and the cost-effectiveness of changing the medication cycle of zoledronic acid were explored through scenario analysis. RESULTS Denosumab regimen was more effective than zoledronic acid regimen （12.77 QALYs vs. 11.98 QALYs），and its cost was also higher than zoledronic acid regimen （51 224.56 yuan vs. 49 221.67 yuan）， and the incremental cost-effectiveness ratio was 2 544.14 yuan/QALY. One-way sensitivity analysis showed that the cost of Zoledronic acid injection and that of Denosumab injection had great impact on the results. The results of probabilistic sensitivity analysis showed that when using 3 times of per capita gross domestic product （GDP）in China in 2021 as the threshold of willingness to pay ，the probability of Denosumab regimen being cost-effective was 85.4％. The results of the scenario analysis showed that the Denosumab regimen was still more cost-effective when the dosing cycle of zoledronic acid was changed. CONCLUSIONS Under the threshold of 1-3 times of Chinese per capita GDP in 2021，denosumab combined with calcium carbonate D 3 is more cost-effective than zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis.

Systematic review of the economical efficiency of drugs for anapastic lymphoma kinase-positive non-small cell lung cancer / 中国药房

OBJECTIVE To systematically evaluate the economical efficiency of marketed a naplastic lymphoma kinase （ALK）-tyrosine kinase inhibitors （TKI）for the treatment of ALK-positive non-small cell lung cancer （NSCLC）in China ，and to provide a reference for the selection of China ’s medical insurance list and drug pricing. METHODS Computer searches of databases such as CNKI ，Wanfang database ，VIP，PubMed，Embase and the Cochrane Library were conducted to collect pharmacoeconomic evaluation studies of four marketed ALK-TKI （crizotinib，seretinib，aletinib and ensatinib ）in the treatment of ALK-positive NSCLC in China during the inception to July 2021. The qualities of the included literature were evaluated using CHEERS checklist ，and analyzed systematically in terms of both methodological and economic outcomes. RESULTS A total of 6 literatures were included ，with a compliance rate of 71％ to 83％ for the CHEERS list criteria ，and the overall quality of the literature was high. In terms of methodological analysis ，the pharmacoeconomic evaluation methods included in the study were mainly model-based （Markov or partitioned survival models ） and real-world data-based cost-utility analysis. Most research perspectives were health insurance payer and health system perspectives ；all cost types were direct medical costs. In terms of economical efficiency analysis ，compared with chemotherapy plan ，2 studies confirmed that ALK-TKI （crizotinib，seretinib）were not economic ，1 study confirmed ALK-TKI （crizotinib） showed economical efficiency. Seretinib showed relatively higher economical efficiency when compared to other ALK-TKIs. High drug prices were the main factor why ALK-TKI was not economically viable for treating ALK-positive NSCLC. CONCLUSIONS The second-generation ALK-TKI （seretinib， 163.com alectinib） have better economical efficiency than the first-generation ALK-TKI （crizotinib）. The economical efficiency of seretinib is the best among the second-generation · ALK-TKI. The economical efficiency of chemotherapy regimen is better than that of the second-generation ALK-TKI （seretinib）. Economic comparison between chemotherapy and first-generation ALK-TKI （crizotinib）remains controversial.

Cost-utility analysis of pembrolizumab combined with chemotherapy in the first-line treatment of advanced or metastatic esophageal carcinoma / 中国药房

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

Two new Polyangium species, P. aurulentum sp. nov. and P. jinanense sp. nov., isolated from a soil sample.

Polyangium belongs to Polyangiaceae family of Myxococcales, a taxonomic group well-known for their extraordinary social lifestyle and diverse novel gene clusters of secondary metabolites. A yellow-golden strain, designated SDU3-1T, and two rose pink strains, designated SDU13 and SDU14T, were isolated from a soil sample. These three strains were aerobic, mesophilic, not salt-tolerant and were able to prey on living microorganisms. SDU13 and SDU14T formed solitary sporangioles under starvation conditions, while SDU3-1T had no fruiting body structures. They showed 95.9-97.0% (SDU3-1T) or 98.7-98.9% (SDU13 and SDU14T) 16S rRNA gene similarity with the type strains of Polyangium, but were phylogenetically separate from them based on the 16S rRNA gene and genome sequences. Their genomes were 12.3 Mbp (SDU3-1T), 13.9 Mbp (SDU13) and 13.8 Mbp (SDU14T) with the G + C content range of 68.3-69.4 mol%. The average nucleotide identity and DNA-DNA hybridization analyses of genomes further indicated that these three strains belonged to two new species in Polyangium. Their major fatty acids were C18:1ω9c, C16:0 and C18:0. The polyphasic taxonomic characterization suggest that the three strains represent two novel species in the genus Polyangium, for which the names Polyangium aurulentum sp. nov. and Polyangium jinanense sp. nov. are proposed, and the type strains are SDU3-1T (=CGMCC 1.16875T = KCTC 72136T) and SDU14T (=CCTCC AB 2021123T = KCTC 82625T), respectively.