Subsequent surgical treatment or maintenance immunotherapy in stage III lung cancer patients achieving a favorable response following neoadjuvant immunotherapy: A matched retrospective cohort study from the surgical perspective.

BACKGROUND: Current treatment strategies for advanced non-small cell lung cancer (NSCLC) are highly individualized and subject to ongoing debates. In the era of immunotherapy, surgery assumes a critical role. The aim of this study was to investigate if subsequent surgical intervention, following a favorable response to immunotherapy and chemotherapy, could yield a more favorable prognosis for patients with advanced stage III NSCLC compared to the continuation of immunotherapy and chemotherapy. METHODS: We included patients whose tumors exhibited a favorable response (including partial response [PR] and complete response [CR]) to immunotherapy and chemotherapy. These patients were categorized into two groups based on their subsequent treatment plans: surgical and nonsurgical (continuation of maintenance immunotherapy and chemotherapy). The efficacy and long-term prognosis of these groups were compared after matching them in a 1:1 ratio using propensity scores. RESULTS: In total, 186 patients (93 in each group) were included in this study after matching via propensity scores. The 1- and 3-year overall survival (OS) and progression-free survival (PFS) rates were 96.0%, 88.5%, and 93.1%, 80.7% in the surgical group, and 93.2%, 83.1%, and 57.7%, 50.4% in the nonsurgical group, respectively. Patients in the surgical group exhibited significantly superior PFS and OS compared to those in the nonsurgical group (p = 0.025 and p = 0.00086). Univariate and multivariate analyses confirmed ΔBMI, Δtumor size reduction, tumor response, earlier clinical stage (IIIb vs. IIIa), and surgery as independent protective factor for patient prognosis. We further selected 101 patients with CR (39 in the surgical group and 62 in the nonsurgical group) and found that patients in the surgical group were significantly better in both PFS and OS. Our subgroup analysis in postoperative patients demonstrated that different surgical strategies did not significantly affect the long-term prognosis of patients (PFS and OS) but could impact their perioperative experience. CONCLUSION: Patients with advanced stage III NSCLC, whose tumors achieved PR and CR after 2-4 cycles of immunotherapy combined with chemotherapy, experience a more promising prognosis with subsequent surgical intervention compared with the continued immunotherapy. Despite encountering formidable obstacles, such as protracted surgical procedures and associated trauma, we must rise to the challenge and unleash the power of surgery after immunotherapy in advanced NSCLC.

Recent advances in understanding the interfacial activity of antioxidants in association colloids in bulk oil.

The chemical stability of edible oils rich in polyunsaturated fatty acids (PUFAs) is a major challenge within the food and supplement industries, as lipid oxidation reduces oil quality and safety. Despite appearing homogeneous to the human eye, bulk oils are actually multiphase heterogeneous systems at the nanoscale level. Association colloids, such as reverse micelles, are spontaneously formed within bulk oils due to the self-assembly of amphiphilic molecules that are present, like phospholipids, free fatty acids, and/or surfactants. In bulk oil, lipid oxidation often occurs at the oil-water interface of these association colloids because this is where different reactants accumulate, such as PUFAs, hydroperoxides, transition metals, and antioxidants. Consequently, the efficiency of antioxidants in bulk oils is governed by their chemical reactivity, but also by their ability to be located close to the site of oxidation. This review describes the impact of minor constituents in bulk oils on the nature of the association colloids formed. And then the formation of mixed reverse micelles (LOOH, (co)surfactants, or antioxidations) during the peroxidation of bulk oils, as well as changes in their composition and structure over time are also discussed. The critical importance of selecting appropriate antioxidants and surfactants for the changes of interface and colloid, as well as the inhibition of lipid oxidation is emphasized. The knowledge presented in this review article may facilitate the design of bulk oil products with improved resistance to oxidation, thereby reducing food waste and improving food quality and safety.

Green manufacturing for achieving carbon neutrality goal requires innovative technologies: A bibliometric analysis from 1991 to 2022.

Recent years have seen a significant increase in interest in green manufacturing as a key driver of global carbon-neutral efforts and sustainable development. To find the research hotspots of green manufacturing and reveal future research trends, this study reviewed and analyzed research articles from the Web of Science database on green manufacturing from 1991 to 2022 using a bibliometric method. The findings indicate a significant rise in the number of articles related to green manufacturing since the 2010s. Moreover, there has been an increase in the involvement of scholars from developing countries such as China and India in this field. Based on the literature review and bibliometric cluster analysis on green manufacturing, we believed that future research may continue following the lines of intelligent technology integration, adoption of frontier engineering techniques, and industry development in line with carbon reduction targets. A framework for future green manufacturing development is proposed, with a focus on Chinese policies. The framework could provide policy implications for developing countries looking to pursue opportunities for development in green manufacturing.

On the Microstructural Evolution and Cracking Behavior of a Titanium Aluminide Alloy During Selective Laser Melting.

Selective laser melting of Ti-48Al-2Cr-2Nb usually ends up with serious cracking. The cracking mechanism, however, remains elusive. In this study, both bulk samples and samples containing only several layers were prepared and investigated. It is shown that a freshly built layer is dominated by single α2 phase. γ started to form from α2 during subsequent thermal cycling due to reheating effects and its volume fraction increased continuously with increased thermal cycles. The γ phase contains higher geometrically necessary dislocation (GND) density than α2. This could be due to its relatively lower hardness and higher thermal expansion coefficient, which made it easier to deform under stresses. With higher GND and thus probably higher distortion energy, the γ experienced more extensive recrystallization than α2 during reheating. Cracks are more liable to initiate from the interior of α2 or the γ/α2 interfaces, which could be due to incompatible deformation between the two phases.

Fine mapping of powdery mildew resistance gene PmXNM in a Chinese wheat landrace Xiaonanmai.

KEY MESSAGE: Powdery mildew resistance gene PmXNM, originated from the Chinese wheat landrace Xiaonanmai, was delimited to a 300.7-kb interval enriched with resistance genes. Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease threatening the yield and quality of wheat worldwide. The use of broad-spectrum disease resistance genes from wheat landraces is an effective strategy to prevent this pathogen. Chinese wheat landrace Xiaonanmai (XNM) was immune to 23 tested Bgt isolates at the seedling stage. The F1, F2, and F2:4 progenies derived from the cross between XNM and Chinese Spring (CS) were used in this study. Genetic analysis revealed that powdery mildew resistance in XNM was controlled by a single dominant gene, temporarily designated PmXNM. Bulked segregant analysis and molecular mapping delimited PmXNM to the distal terminal region of chromosome 4AL flanked by markers caps213923 and kasp511718. The region carrying the PmXNM locus was approximately 300.7 kb and contained nine high-confidence genes according to the reference genome sequence of CS. Five of these genes, annotated as disease resistance RPP13-like proteins 1, were clustered in the target region. Haplotype analysis using the candidate gene-specific markers indicated that the majority of 267 common wheat accessions (75.3%) exhibited extensive gene losses at the PmXNM locus, as confirmed by aligning the targeted genome sequences of CS with those of other sequenced wheat cultivars. Seven candidate gene-specific markers have proven effective for marker-assisted introgression of PmXNM into modern elite cultivars.

Methods for Economic Evaluations of Novel Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is a severe epidemiological and public health concern among the elderly population worldwide, with substantial economic and social burdens. Economic evaluations can play an essential role in optimizing the utilization of scarce resources. In recent years, the number of economic evaluation studies related to AF has increased due to the rising number of AF patients, the continuous updating of clinical data, and the emergence of real-world evidence. However, there are still deficiencies in model settings and parameter sources in relevant studies. OBJECTIVE: This study aims to review the existing economic evaluations of novel oral anticoagulants (NOACs) in patients with AF and summarize the evidence and methods applied. METHODS: A comprehensive and systematic search was conducted on electronic databases, including PubMed, Embase, Web of Science (WOS), and The Cochrane Library, from the date of database creation to November 2022. The reporting quality of included literature was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement. RESULTS: A total of 102 studies were included in the review, with 200 comparisons between NOACs and vitamin K antagonists (VKAs), as well as 58 comparisons between different NOACs. The healthcare sector and payer perspectives were the most common, and accordingly, the majority of the evaluations considered only direct medical costs. Most studies used Markov cohort models with the number of health states ranging from 4 to 29. Of included studies, 80 (78%) considered event recurrence and complications, and 78 (76%) considered discontinuation and second-line therapy. All of the studies applied uncertainty analysis to explore the robustness of the results. Of all 200 NOACs-VKAs comparisons, 149 (75%) showed that NOACs were more cost-effective; this proportion was 84% (139 out of 165) in high-income countries but decreased to 29% (10 out of 35) in middle- and low-income countries. Most (82%) of the 28 items in the CHEERS 2022 checklist were elucidated in the majority of included studies. A minority (only 39%) of included studies demonstrated high reporting quality. CONCLUSION: NOACs may be more cost-effective than VKAs in patients with AF, but this conclusion applies to high-income countries, whereas VKAs may be more cost-effective in middle- and low-income countries. The reporting quality of included studies was variable, and certain methodological issues were presented. This study highlights the economic evaluation methodology of NOACs in patients with AF and provides recommendations for modeling methods and future studies.

Bronchobiliary fistula caused after percutaneous transhepatic biliary drainage treatment: A case report.

RATIONALE: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the diagnosis and decompression of bile duct obstruction. However, it is associated with complications such as hemobilia, occlusion of drainage, bile leakage, and even bronchobiliary fistula (BBF). PATIENT CONCERNS AND DIAGNOSES: We herein describe a patient with a complication of BBF caused by long-term indwelling PTBD catheters. She underwent multiple operations including bilioenteric anastomosis, hepatic left lateral lobectomy, and long-term PTBD treatment. Her symptoms were mainly cough, fever, and yellow sputum and her diagnosis was confirmed by sputum culture (bilirubin detection was positive). INTERVENTIONS AND OUTCOMES: The patient recovered uneventfully by minimally invasive treatment, was discharged after 1 week of hospitalization, and the drainage tube was removed 2 weeks later. During 2 years of follow-up, no recurrence of BBF was observed. LESSONS: Patients with long-term indwelling PTBD catheters for biliary tract obstruction may lead to BBF. The treatment plan of BBF is tailored to the patient's individualized characteristics. And minimally invasive treatments might be an effective alternate way for the treatment of BBF. The accurate diagnosis, precision treatment, and multidisciplinary team play important roles in the treatment of BBF.

Effect of Different Temperatures on the Storage Stability of Flaxseed Milk.

In this study, the physical and oxidative stability of flaxseed milk without food additives at different temperatures (25 °C and 37 °C) was assessed. Over in 206 days in storage, the particle size, Turbiscan stability index (TSI), centrifugal sedimentation rate, and primary and secondary oxidation products of flaxseed milk increased, viscosity decreased, and the absolute value of the potential first decreased and then increased. These phenomena indicated a gradual decrease in the physical stability of flaxseed milk, accompanied by drastic oxidative changes. The antioxidant capacity of flaxseed milk was related to the location of the physical distribution of flaxseed lignin, which was more effective in the aqueous phase compared to the non-aqueous phase. Interestingly, after 171 days in storage at 37 °C, the particle size of flaxseed milk was approximately doubled (6.98 µm → 15.27 µm) and the absolute value of the potential reached its lowest point (-13.49 mV), when the content of primary oxidation products reached its maximum (8.29 mmol/kg oil). The results showed that temperature had a significant effect on the stability of flaxseed milk and that stability decreased with increasing temperature and shortened shelf life. This work provides a theoretical basis for elucidating the stabilization-destabilization mechanism of flaxseed milk.

Saikosaponin-d regulates angiogenesis in idiopathic pulmonary fibrosis through angiopoietin/Tie-2 pathway.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is considered as a chronic interstitial lung disease with underlying mechanism of IPF remaining unclear, while there are no definitive treatment options. In recent years, scientists have gradually paid attention to the influence of angiogenesis on IPF. Because IPF is a progressive with microvascular remodeling disorder, scientists have postulated that angiogenesis may also be one of the initiating and contributing factors of the disease. Bupleurum is a common natural Chinese herbal medicine with antibacterial, anti-inflammatory, anti-tumor and other pharmacological effects. As the most important active monomer of Bupleurum, Saikosaponin-d (SSd) is a new discovery with anti-pulmonary fibrosis (PF) activity. This study attempts to investigate the role of SSd in the interference of PF through regulation of angiogenesis in IPF through Angiopoietin (Angpt) /Tie receptor 2 (Tie2) pathway. METHODS: Randomly, we allocated C57BL/6 mice into four groups (n = 20 in each group). Afterwards, establishment of IPF model was accomplished via intratracheal administration of bleomycin (BLM, 5 mg/kg), while corresponding drug intervention was given accordingly. On 3rd, 7th, 14th and 28th days after modeling, we performed histopathological examination through staining. Meanwhile, immunohistochemistry (IHC) of PF and the expression of related factors were observed, while Ang/Tie2 pathway was assessed by ELISA with the effect of SSd on angiogenesis related proteins in IPF being explored with IHC and Western Blot technique. RESULTS: Our results showed that SSd could reduce inflammation and PF levels in lung tissue of experimental mice, while levels of angiogenesis-related factors, namely Tie-2, Ang-1 and ANGPT2 (Ang-2), fibrosis- associated factors like Alpha-smooth muscle actin (α-SMA), collagen-I and hydroxyproline in SSd and dexamethasone (DXM) mice were significantly reduced at each time point compared to BLM (p < 0.01). Additionally, we discovered substantial decreased expressions of Ang-1, Ang-2, Tie-2, α-SMA and collagen-I at protein level in SSd and DXM mice at each time point compared to BLM (p < 0.05). Besides, insignificant differences were observed between SSd and DXM groups (p > 0.05). CONCLUSION: This study has demonstrated that SSd could down-regulate the expression of ANG-1, Ang-2 and Tie2 in the Ang/Tie2 pathway, and may reduce lung inflammation and PF in BLM-induced mice via inhibition of angiogenesis.

MC design and FIB preparation of a YSZ biochemical material microstructure.

Aiming at the difficulty of traditional machining of Y2O3-ZrO2 (YSZ) inert ceramic materials, a different method using focused ion beam to selectively create nanoscale microscale structures on the surface of materials was proposed. The sputtering yield, surface damage, and the energy loss of YSZ materials was investigated using the SRIM software using the Monte Carlo method. It is shown that the sputtering yield increases with ion energy in the range 0-30 keV, reaching a maximum of 9.4 atoms/ion at 30 keV. At an ion beam voltage of 30 keV, the most severe damage to the material is 8 mm on the surface. At the same time, the main forms of energy loss in the treatment are phonon energy loss and ionization energy loss, of which phonon energy loss due to the recoil atoms is the largest. In addition, we continue to perform focused ion beam processing experiments on YSZ materials, combining previous MC modeling to optimize different operating conditions such as ion beam, voltage and processing mode. The optimized processing parameters are 30 keV and 2.5 nA. It is shown that the quality of the deep grooves gradually improves with decreasing ion beam current at the same ion beam voltage. However, an excessively small ion beam current leads to an excessively large depth of the deep grooves and lengthy processing times.

SIgA in various pulmonary diseases.

Secretory immunoglobulin A (SIgA) is one of the most abundant immunoglobulin subtypes among mucosa, which plays an indispensable role in the first-line protection against invading pathogens and antigens. Therefore, the role of respiratory SIgA in respiratory mucosal immune diseases has attracted more and more attention. Although the role of SIgA in intestinal mucosal immunity has been widely studied, the cell types responsible for SIgA and the interactions between cells are still unclear. Here, we conducted a wide search of relevant studies and sorted out the relationship between SIgA and some pulmonary diseases (COPD, asthma, tuberculosis, idiopathic pulmonary fibrosis, COVID-19, lung cancer), which found SIgA is involved in the pathogenesis and progression of various lung diseases, intending to provide new ideas for the prevention, diagnosis, and treatment of related lung diseases.

Cardamonin protects against iron overload induced arthritis by attenuating ROS production and NLRP3 inflammasome activation via the SIRT1/p38MAPK signaling pathway.

Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.

The cost-effectiveness analysis of serplulimab versus regorafenib for treating previously treated unresectable or metastatic microsatellite instability-high or deficient mismatch repair colorectal cancer in China.

Objective: The aim of this study was to investigate the cost-effectiveness of serplulimab versus regorafenib in previously treated unresectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancer in China. Methods: From the perspective of China's health-care system, a Markov model with three health states (progression free, progression, death) was developed for estimating the costs and health outcomes of serplulimab and regorafenib. Data for unanchored matching-adjusted indirect comparison (MAIC), standard parametric survival analysis, the mixed cure model, and transition probabilities calculation were obtained from clinical trials (ASTRUM-010 and CONCUR). Health-care resource utilization and costs were derived from government-published data and expert interviews. Utilities used to calculate quality-adjusted life years (QALYs) were obtained from clinical trials and literature reviews. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained. Four scenarios were considered in scenario analysis: (a) using original survival data without conducting MAIC; (b) limiting the time horizon to the follow-up time of the clinical trial of serplulimab; (c) adopting a fourfold increase in the risk of death; and (d) applying utilities from two other sources. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed to assess the uncertainty of the results. Results: In the base-case analysis, serplulimab provided 6.00 QALYs at a cost of $68,722, whereas regorafenib provided 0.69 QALYs at a cost of $40,106. Compared with that for treatment with regorafenib, the ICER for treatment with serplulimab was $5,386/QALY, which was significantly lower than the triple GDP per capita of China in 2021 ($30,036), which was the threshold used to define the cost-effectiveness. In the scenario analysis, the ICERs were $6,369/QALY, $20,613/QALY, $6,037/QALY, $4,783/QALY, and $6,167/QALY, respectively. In the probabilistic sensitivity analysis, the probability of serplulimab being cost-effective was 100% at the threshold of $30,036/QALY. Conclusion: Compared with regorafenib, serplulimab is a cost-effective treatment for patients with previously treated unresectable or metastatic MSI-H/dMMR colorectal cancer in China.

"Internet+ Recycling" Platform Participation Selection Strategy in a Two-Echelon Remanufacturing Closed-Loop Supply Chain.

Compared with traditional offline recycling channel, recycling through the "Internet+ recycling" platform has increasingly attracted the academic and practical intention in the past decade because of its accessibility and convenience. To promote the recycling initiatives and construct sustainable operations, how to stimulate supply chain stakeholders participating in the online recycling becomes a challenge issue. This paper considers one supplier, one manufacturer, and one third-party recycler (3PR) in a two-echelon remanufacturing closed-loop supply chain with an "Internet+ recycling" platform, in which consumers can access the online recycling platform and make an appointment for recycling without a physical visit. The manufacturer has three choices: either do not participate or participate with one of two strategies: cost-sharing (CS) or active promotion (AP) strategy. We develop a Stackelberg game model to study the motivation of the manufacturer to participate in the "Internet+ recycling" platform and the influence mechanism of key factors. The key findings include the following: (1) compared with the case without the "Internet+ recycling" platform, when the proportion of cost sharing for the 3PR is low, strategy CS contributes to the improvement of the 3PR's performance; (2) in the presence of two participation strategies, when the disassembly rate is low enough, the manufacturer prefers strategy AP; otherwise, he selects strategy CS; and (3) a high proportion of cost sharing for the manufacturer or low promotion effort cost can increase the whole profit of the closed-loop supply chain.

Neoadjuvant immunotherapy combined with chemotherapy significantly improved patients' overall survival when compared with neoadjuvant chemotherapy in non-small cell lung cancer: A cohort study.

Background: Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC. Methods: We retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared. Results: A total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P<0.001) and major pathologic response (MPR) rate (78.95% vs. 10.26%, P<0.001). There were no differences in survival curves for: smoker and non-smoker, squamous cell carcinoma and adenocarcinoma, or right lung cancer and left lung cancer. Moreover, patients who achieved MPR (including pCR) had significantly better overall survival (OS) and disease-free survival (DFS). Patients in immunotherapy group had significantly better OS and longer DFS than those in chemotherapy group. Conclusions: In conclusion, neoadjuvant immunotherapy combined with chemotherapy can provide better OS and DFS and improving pCR and MPR rates by shrinking tumors.This study has been registered in the Chinese Clinical Trial Registry, number ChiCTR2200060433. http://www.chictr.org.cn/edit.aspx?pid=170157&htm=4.

Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma.

BACKGROUND: In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC. METHODS: A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model. RESULTS: Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively. CONCLUSION: Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

Development and preliminary validation of a public health emergency competency model for medical staffs of national health emergency teams in China.

BACKGROUND: In the present study, we attempted to develop and validate a participatory competency model for medical workers and then evaluate the current status of competency characteristics of Chinese medical workers. METHODS: The competency model was constructed in a multistage process, including literature review, expert consultation, critical incident and focus group interview. A pilot study was conducted to refine the initial model among 90 participators and the viability and reliability were evaluated by a questionnaire survey among 121 medical workers. Then, the current status of competency characteristics was measured based on the final version of competency model. RESULTS: In the pilot study, ten questionnaires were dropped for the poor quality and thus the eligible rate was 92% (138/150). KMO value was 0.785 and Bartlett test showed that the χ2 = 6464.546 (df = 903) and p value < 0.001. Then, 10 items with double loading and factor loading < 0.4 were deleted. Finally, 33 items were retained with the lowest factor loading value of 0.465. The validity and reliability of competency model were determined with Cronbach's α coefficient of 0.975 and ICC value of 0.933. Finally, a revised competency model with 5 dimensions and 31 items was obtained. The overall competencies of current medical workers were in a high level, except for emergency knowledge related competencies. Age was an independent factor affecting the competencies. CONCLUSIONS: Our competency model was a reliable and validated tool for assessing the competences of medical staffs against public health emergencies, and the overall competencies of current medical workers in China were in a high level, except for emergency knowledge related competencies.

Economic evaluation of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for the treatment of first-line advanced or metastatic squamous NSCLC.

Background and objective: Sintilimab has superior efficacy and safety in patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC), but its cost-effectiveness in China is unclear. This study is to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for locally advanced or metastatic squamous NSCLC in China. Methods: From the perspective of the Chinese health system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime time horizon. The two-stage method was used to estimate the overall survival hazard ratios to avoid the bias by crossover design in ORIENT-12 and KEYNOTE-407 studies. The anchored matching adjusted indirect comparison method (MAIC) was used for indirect comparison based on the individual patient data from ORIENT-12 and the publicly published KEYNOTE-407 study due to the lack of head-to-head clinical trials. Only direct medical costs were included, and utilities were derived from the published literature in the base case analysis. Sensitivity analysis was also performed to verify the robustness of the model results. In addition, the scenario analysis where the utilities were derived from the Quality of Life Questionnaire-Core 30 (QLQ-C30) scale in the ORIENT-12 by mapping to the EuroQol-5-dimension 5-level (EQ-5D-5L) was carried out to explore the uncertainty of the results. Results: Compared with pembrolizumab + chemotherapy, sintilimab + chemotherapy incurred a lower lifetime cost ($12,321 vs. 36,371) and yielded fewer quality-adjusted life-years (QALYs) (0.9902 vs. 1.0085), which resulted in an incremental cost-effectiveness ratio (ICER) of $1,314,208/QALY. A sintilimab strategy is a cost-effectiveness option under the WTP of 1-3 times the GDP per capita in China ($11,250/QALY~$33,749/QALY). The utility value of the post-progression, the unit cost of albumin paclitaxel, and the utility value of the progression-free state were the main drivers in the deterministic sensitivity analysis (DSA). According to the probabilistic sensitivity analysis (PSA), sintilimab + chemotherapy was 100% cost-effective when the WTP was 1-3 times China's per capita GDP. The results of the scenario analysis showed that sintilimab + chemotherapy obtained more QALYs (1.2319 vs. 1.1815) and lower costs ($12,321 vs. 36,371), which implied that sintilimab + chemotherapy may dominate the pembrolizumab + chemotherapy. Conclusion: Compared with pembrolizumab + chemotherapy, sintilimab + chemotherapy is more cost-effective for first-line treatment in Chinese patients with locally advanced or metastatic squamous NSCLC.

Effect of Tempering Temperature on Microstructure and Sulfide Stress Cracking of 125 Ksi Grade Casing Steel.

The influence of tempering temperature on the microstructure of 0.5Cr0.4W steels was investigated by scanning electron microscope, and the roles of grain boundary character, dislocation, and Taylor factor in sulfide stress cracking (SSC) resistance were interpreted using the election backscattered diffraction technique. The 0.5Cr0.4W steels tempered at 690 °C, 700 °C, and 715 °C all showed tempered martensites. The specimen tempered at 715 °C exhibited a higher critical stress intensity factor (KISSC) of 34.58 MPa·m0.5, but the yield strength of 800 MPa did not meet the criterion of 125 ksi (862 MPa) grade. When the specimen was tempered at 690 °C, the yield strength reached 960 MPa and the KISSC was only 21.36 MPa·m0.5, displaying poorer SSC resistance. The 0.5Cr0.4W steel tempered at 700 °C showed a good combination of yield strength (887 MPa) and SSC resistance (KISSC: 31.16 MPa·m0.5). When increasing the tempering temperature, the local average misorientation and Taylor factor of the 0.5Cr0.4W steels were decreased. The reduced dislocation density, and greater number of grains amenable to slippage, produced less hydrogen transport and a lower crack sensitivity. The SSC resistance was, thus, increased, owing to the minor damage to hydrogen aggregation. Therefore, 700 °C is a suitable tempering temperature for 0.5Cr0.4W casing steel.

Economic Evaluation of Sintilimab Plus Bevacizumab Versus Sorafenib as a First-line Treatment for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: This study aimed to evaluate the cost-effectiveness of sintilimab plus bevacizumab versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma (HCC) in China to provide economic evidence to inform health decision making. METHODS: We performed an economic evaluation from the perspective of the Chinese healthcare system using a partitioned survival model with three mutually exclusive health states: progression free, post-progression, and death. Efficacy data were obtained from the ORIENT-32 clinical trial and extrapolated to the lifetime horizon. Cost and utility values were derived from published studies and online price databases. The primary outcomes of the model were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were carried out to verify the robustness of the model results. RESULTS: Compared with sorafenib, sintilimab plus bevacizumab incurred a higher lifetime cost ($33,766 vs. $23,294) and yielded more QALYs (1.428 vs. 0.928 QALYs). The ICER for sintilimab plus bevacizumab was $20,968/QALY and lower than the willingness-to-pay threshold of $33,592. The results of sensitivity analysis showed that ICER values were most sensitive to the subsequent treatment cost of the sorafenib group after progression and the price of bevacizumab. In the scenario analysis, the ICER was $4191/QALY when a 7.5 mg/kg dose of bevacizumab was applied in the model. CONCLUSIONS: Compared with sorafenib, the sintilimab plus bevacizumab combination is likely to be a cost-effective option for patients with unresectable HCC in China.