Effects of ambient temperature and humidity on COPD mortality in Ganzhou city, China.

This study used the time series data of Ganzhou city to explore the individual and interaction effects of temperature and humidity on COPD death, and identify vulnerable subgroups of the population. We collected daily COPD mortality and meteorological data in Ganzhou from 2016 to 2019. The nonlinear distribution lag model was used to examine the associations and interaction between daily mean temperature and humidity and COPD mortality. For the total population, male and 65 years old or above, the relative risk (RR) for COPD mortality could be significant at extremely low temperature (3.3 ℃), reaching 1.799 (95% confidence interval [CI]: 1.216, 2.662), 1.894 (95% CI: 1.164, 3.084) and 1.779 (95% CI:1.185, 2.670). Also, at extremely low humidity (47.8%), the risk reached 1.888 (95% CI: 1.217, 2.930), 1.837 (95% CI: 1.066, 3.165) and 2.166 (95% CI: 1.375, 3.414). The cumulative COPD death risk for females was 3.524 (95% CI: 1.340, 9.267) at high temperature (30.7 ℃), 1.953(95% CI: 1.036, 3.683) at low humidity (47.8%) and 1.726 (95% CI: 1.048, 2.845) at high humidity (96.7%). For the total COPD deaths and subgroups, the interaction effects between daily temperature and humidity were not significant (p > 0.05). Both extremely low temperature and low humidity increased the risk of COPD death in Ganzhou city, especially for males and people over 65 years old. Females were more sensitive to extremely high temperature and humidity. Patients with COPD should pay attention to self-protection under extreme temperature and humidity weather conditions.

Cost-utility analysis and drug pricing for tirzepatide for type 2 diabetes in the Chinese market compared with semaglutide.

AIM: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. METHODS: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. RESULTS: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. CONCLUSIONS: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China.

Suppressed Phase Segregation with Small A-Site and Large X-Site Incorporation for Photostable Wide-Bandgap Perovskite Solar Cells.

Wide-bandgap (WBG) perovskite solar cells (PSCs) have been widely used as the top cell of tandem solar cells. However, photoinduced phase segregation and high open-circuit voltage loss pose significant obstacles to the development of WBG PSCs. Here, a two-step small-size A-site and large-size X-site incorporation strategy is reported to modulate the lattice distortion and improve the film quality of WBG formamidinium-methylammonium (FAMA) perovskite films for photostable PSCs based on two-step deposition method. First, CsI with content of 0-20% is introduced to tune the lattice distortion and film quality of FAMA perovskite with a bandgap of 1.70 eV. Then, 4% RbI is incorporated to further modulate the perovskite growth and lattice distortion, leading to the suppression of photoinduced phase segregation in the resultant RbCsFAMA quadruple cation perovskites. As a result, the 20%CsI/4%RbI-doped device obtains a promising efficiency of 20.6%, and the corresponding perovskite film shows good photothermal stability. Even without encapsulation, the device can maintain 92% of its initial efficiency after 1000 h of continuous operation under 1 sun equivalent white light-emitting diode illumination.

Thermodynamic Analysis of Silk Fibroin-Graphite Hybrid Materials and Their Morphology.

Silk fibroin (SF) is a ß-sheet-rich protein that is responsible for the remarkable tensile strength of silk. In addition to its mechanical properties, SF is biocompatible and biodegradable, making it an attractive candidate for use in biotic/abiotic hybrid materials. A pairing of particular interest is the use of SF with graphene-based nanomaterials (GBNs). The properties of this interface drive the formation of well-ordered nanostructures and can improve the electronic properties of the resulting hybrid. It was previously demonstrated that SF can form lamellar nanostructures in the presence of graphite; however, the equilibrium morphology and associated driving interactions are not fully understood. In this study, we characterize these interactions between SF and SF lamellar with graphite using molecular dynamics (MD) simulations and umbrella sampling (US). We find that SF lamellar nanostructures have strong orientational and spatial preferences on graphite that are driven by the hydrophobic effect, destabilizing solvent-protein interactions and stabilizing protein-protein and protein-graphite interactions. Finally, we show how careful consideration of these underlying interactions can be applied to rationally modify the nanostructure morphology.

Biomimetic Mineral Synthesis by Nanopatterned Supramolecular-Block Copolymer Templates.

Supramolecular structures of matrix proteins in mineralizing tissues are known to direct the crystallization of inorganic materials. Here we demonstrate how such structures can be synthetically directed into predetermined patterns for which functionality is maintained. The study employs block copolymer lamellar patterns with alternating hydrophilic and hydrophobic regions to direct the assembly of amelogenin-derived peptide nanoribbons that template calcium phosphate nucleation by creating a low-energy interface. Results show that the patterned nanoribbons retain their ß-sheet structure and function and direct the formation of filamentous and plate-shaped calcium phosphate with high fidelity, where the phase, amorphous or crystalline, depends on the choice of mineral precursor and the fidelity depends on peptide sequence. The common ability of supramolecular systems to assemble on surfaces with appropriate chemistry combined with the tendency of many templates to mineralize multiple inorganic materials implies this approach defines a general platform for bottom-up-patterning of hybrid organic-inorganic materials.

In Situ Polymerized Flame Retardant Gel Electrolyte for High-Performance and Safety-Enhanced Lithium Metal Batteries.

A flame retardant gel electrolyte (FRGE) is deemed as one of the most promising electrolytes to relieve the problems of safety hazards and interfacial incompatibility of Li metal batteries. Herein, a novel solvent triethyl 2-fluoro-2-phosphonoacetate (TFPA) with outstanding flame retardancy is introduced in the polymer skeleton synthesized by in situ polymerization of the monomer polyethylene glycol dimethacrylate (PEGDMA) and the cross-linker pentaerythritol tetraacrylate (PETEA). The FRGE exhibits superb interfacial compatibility with Li metal anodes and inhibits uncontrolled Li dendrite growth. This can be ascribed to the restriction of free phosphate molecules by the polymer skeleton, thus realizing a stable cycling performance over 500 h at 1 mA cm-2 and 1 mAh cm-2 in the Li||Li symmetric cell. In addition, the high ionic conductivity (3.15 mS cm-1) and Li+ transference number (0.47) of the FRGE further enhance the electrochemical performance of the correspondent battery. As a result, the LiFePO4|FRGE|Li cell exhibits excellent long-term cycling life with a capacity retention of 94.6% after 700 cycles. This work points to a new pathway for the practical development of high-safety and high-energy-density Li metal-based batteries.

Potential impacts of climate change on the distribution of the relict plant Shaniodendron subaequale.

Shaniodendron subeaqualis is a tertiary relict plant unique to China. This species has high greening, ecological, and scientific research value, and has been listed as a national I-level key protected plant. Clarifying the main climatic factors restricting the geographical distribution of S. subeaqualis and predicting the potential geographical distribution pattern of this species can provide a scientific basis for the protection of the germplasm resources of this rare species. Based on 104 S. subeaqualis natural distribution records and 9 climate factors, the MaxEnt software was used to predict the potential suitable areas of S. subeaqualis in different periods (LGM, MH, Current, SSP245-2050s, SSP245-2090s, SSP585-2050s, SSP585-2090s). The results showed that the contemporary AUC predicted by MaxEnt is 0.996, with high simulation accuracy; Precipitation in the driest season (Bio17), the average temperature in the coldest season (Bio11) are main factors affecting the distribution of S. subeaqualis. At present, the suitable area of S. subeaqualis is mainly distributed in Jiangsu, Anhui, and Zhejiang province, with a total area of 11.575 × 104 km2, of which the high suitable area is 1.424 × 104 km2 and the medium suitable area is 3.826 × 104 km2. In the LGM, the area of S. subeaqualis was roughly similar to that of the contemporary period, but there was a southward migration phenomenon in some areas, such as the suitable area in the south of Zhejiang. In order to avoid the influence of ice age, S. subeaqualis moved to nearby refuge places, such as Dabie Mountain area of Anhui province, the west of Tianmu Mountain area of Zhejiang province and mountain area of Jiangsu province. In the MH, the suitable area for S. subeaqualis was reduced and moved northward to a small extent. In the future period, the suitable range of S. subeaqualis will not change greatly, but the overall degree of fragmentation will intensify. If effective measures are not taken, it is bound to bring severe challenges to the survival of S. subeaqualis. In order to protect S. subeaqualis germplasm resources more effectively, it is suggested to dynamically monitor the existing S. subeaqualis population and take various measures actively to reduce the negative effects of climate change on S. subeaqualis.

Bidirectional association between NAFLD and gallstone disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Growing evidence indicates an association between NAFLD and gallstone disease (GD), while some does not support this. The aim of this meta-analysis was to evaluate the bidirectional association between NAFLD and GD. RESEARCH DESIGN AND METHODS: Five electronic databases were searched from inception to May 2022. The association was analyzed based on the odds ratio (OR) and 95% confidence interval (CI) with Reviewer Manager 5.3. RESULTS: Ten studies involving 284,512 participants met the criteria for GD predicting the onset of NAFLD. GD patients had a higher incidence of NAFLD (OR:1.48, CI:1.32-1.65, p < 0.00001), especially the incidence of moderate-to-severe NAFLD (OR:1.63; CI:1.40-1.79), with females at a higher risk (OR: 1.84; CI: 1.48-2.29). The inverse association was explored in eight studies involving 326,922 participants. The GD incidence in NAFLD patients was higher (OR:1.71, CI:1.63-1.79, p < 0.00001) and may increase due to female sex (OR: 4.18; CI: 1.21-14.37) and high BMI (OR: 1.80; CI: 1.36-2.56), compared with the non-NAFLD group. Besides, this bidirectional association was also confirmed in the Chinese population. CONCLUSIONS: The findings supported positive concurrent and bidirectional relationships between NAFLD and GD. Therefore, clinicians may alert the possibility of NAFLD in patients with GD and vice versa.

Association between daily temperature and hospital admissions for urolithiasis in Ganzhou, China: a time-series analysis.

Urolithiasis was a global disease and it was more common in southern China. This study looked into the association between daily temperature and urolithiasis hospital admissions in Ganzhou, a large prefecture-level city in southern China. In Ganzhou City from 2016 to 2019, a total of 60,881 hospitalized cases for urolithiasis from 69 hospitals and meteorological data were gathered. The effect of high ambient temperature on urolithiasis hospital admissions was estimated using a distributed lag nonlinear model. Stratified analysis was done to examine sex differences. The study found that in Ganzhou of China, the exposure-response curves approximated a "J" shape which across genders were basically similar. The maximum lag effect occurred on the second day after high temperatures for males but on the third day for females. Compared to the 10 °C reference temperature and considering the cumulative lag effect of 10 days, the relative risks of the daily mean temperature at the 95th percentile on the total, male, and female hospital admissions for urolithiasis were 2.026 (95% CI: 1.628, 2.521), 2.041 (95% CI: 1.603, 2.598), and 2.030 (95% CI: 1.552, 2.655), respectively, but the relative risks between sex were not statistically significant (p = 0.977). Urolithiasis morbidity risk in China could be exacerbated by high temperatures. The effect of high temperature on urolithiasis was similar across genders.

Cost-utility analysis of semaglutide for type 2 diabetes after its addition to the National Medical Insurance System in China.

INTRODUCTION: The main research purpose is to compare the long-term cost-effectiveness of semaglutide (SEMA) with that of dulaglutide (DULA) for patients with inadequately controlled type 2 diabetes throughout their lifetime. If necessary, the second aim is to investigate a further price cut for SEMA to provide sound advice for government drug price adjustments. METHODS: Cost-utility analysis was performed by the United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS OM2) from the perspective of health care providers in China. Baseline characteristics and clinical efficacy of SEMA and DULA were sourced from the high-dose comparison in the SUSTAIN-7 trial. A binary search was used to identify the scope for further reduction in the price of SEMA. The impact of individual parameters was assessed with sensitivity analyses. RESULTS: Main analysis (SEMA vs. DULA) revealed a mean difference in quality-adjusted life years (QALYs) of 0.04 QALYs and costs of $1132.29. The incremental cost-utility ratio was $26 957.44/QALY, showing that SEMA was a better option compared with DULA. In sensitivity analyses, the discount rate made the greatest contribution to the incremental cost-utility ratio. In the binary search, there was still scope to reduce the SEMA cost further by approximately 6.83% to be cost-effective, taking DULA as a reference. CONCLUSION: After its addition to the National Medical Insurance System in China, SEMA is expected to be a cost-effective choice compared with DULA for patients with type 2 diabetes with inadequately controlled from the cost-utility analysis. However, there is still scope to reduce the annual cost of SEMA further.

Capture and detection of Escherichia coli with graphene aerogels.

Some pathogenic bacteria may cause serious food poisoning as well as catastrophic infections. Thus, it is critical to identify bacteria using simple, quick, and sensitive methods. Herein, we fabricate a graphene aerogel-based biosensing system to capture and detect Escherichia coli (E. coli) with high specificity and sensitivity. A graphene aerogel is prepared by a one-step hydrothermal synthesis method without any reducing reagent. With the help of E. coli antibodies and the graphene foam with a porous structure, E. coli can be captured using the detection substrate with high specificity and selectivity. The electrical resistance and electrochemical impedance spectroscopy (EIS) results of the graphene aerogel foam changed with high sensitivity during E. coli adhesion. Moreover, the resistance change of the graphene device can still be observed when the E. coli concentration was as low as 10 cfu mL-1, while there is no obvious resistance change in the use of Staphylococcus aureus. The subsequent EIS test also found that the charge transfer resistance (Rct) of the detection substrate gradually increased during the E. coli capture process. This nanoelectronic biosensor is simple, quick, safe, and very sensitive, and it may be used as a high-throughput platform for pathogenic bacterial detection, bacterial research, and antimicrobial drug screening.

Luminescence-enhanced conjugated polymer dots through thermal treatment for cell imaging.

Conjugated polymer dots (Pdots) are often used as excellent fluorescent probes in the biomedical field. In the process of preparing Pdots, the rapid change of the solvent polarity will result in a messy and defective stacking of the polymer chains in the particle, and these stacking defects of the polymer chains may weaken its luminescence properties. Here, we try to optimize the stacking of the conjugated polymer chains by the thermal annealing treatment. After the low temperature thermal treatment, the fluorescence intensity of Pdots can be enhanced by about 11%-29%, and Pdots maintain their original stability and biosafety. We used transmission electron microscopy (TEM) and single particle fluorescence imaging to reveal the possible mechanism of the chain stacking optimization process, that is, the thermal annealing process of Pdots is the competition between internal chain rearrangement in the particle and particle aggregation. The luminescence-enhanced Pdots exhibit good cellular imaging performance. These results prove that it is feasible to extend the thermal annealing treatment from planar polymer devices to polymer nanoparticles. It provides the possibility to realize stable and complex biological imaging applications using Pdots with a simple molecular structure, and a mature improvement scheme for the mass preparation of Pdots.

Blocking CD47 Shows Superior Anti-tumor Therapeutic Effects of Bevacizumab in Gastric Cancer.

Background: Bevacizumab (Avastin®), a humanized antiangiogenic monoclonal antibody, is widely used in the clinical treatment of tumour diseases. However, recent research has shown that the beneficial antiangiogenic effects of these agents have been limited in a number of patients due to complex immunosuppressive mechanisms. Here, we report a synergistic antitumour strategy through simultaneous blockade of VEGF and CD47 signalling to enhance the curative effect of advanced gastric cancer. Method: A BGC-823 gastric tumour model was chosen to evaluate antitumour efficacy. Macrophage migration and phagocytosis were evaluated to determine immune-related resistance to bevacizumab therapy. Synergistic antitumour activity was observed on the basis of tumour volume, tumour weight, tumour inhibition rate, tumour angiogenesis and tumour metastasis when bevacizumab was combined with an anti-CD47 monoclonal antibody. Results: Our study demonstrated that synergistic therapy targeting CD47 and VEGF reversed macrophage migration and phagocytosis, which were inhibited by antiangiogenic therapy and enhanced antitumour effects. Moreover, blockade of CD47 induced by antiangiogenic therapy inhibited tumour metastasis. Conclusion: Our data provide an effective strategy to attenuate resistance to bevacizumab therapy, promoting clinical cancer treatment with antiangiogenic drugs in combination with CD47-targeting inhibitors.

Anisotropic Molecular Organization at a Liquid/Vapor Interface Promotes Crystal Nucleation with Polymorph Selection.

The molecules at the surface of a liquid have different organization and dynamics from those in the bulk, potentially altering the rate of crystal nucleation and polymorphic selection, but this effect remains poorly understood. Here we demonstrate that nucleation at the surface of a pure liquid, d-arabitol, is vastly enhanced, by 12 orders of magnitude, and selects a different polymorph. The surface effect intensifies with cooling and can be inhibited by a dilute, surface-active second component. This phenomenon arises from the anisotropic molecular packing at the interface and its similarity to the surface-nucleating polymorph. Our finding is relevant for controlling the crystallization and polymorphism in any system with a significant interface such as nanodroplets and atmospheric water.

Robust Prediction of Prognosis and Immunotherapy Response for Bladder Cancer through Machine Learning Algorithm.

The important roles of machine learning and ferroptosis in bladder cancer (BCa) are still poorly understood. In this study, a comprehensive analysis of 19 ferroptosis-related genes (FRGs) was performed in 1322 patients with BCa from four independent patient cohorts and a pan-cancer cohort of 9824 patients. Twelve FRGs were selected through machine learning algorithm to construct the prognosis model. Significantly differential survival outcomes (hazard ratio (HR) = 2.09, 95% confidence interval (CI): 1.55−2.82, p < 0.0001) were observed between patients with high and low ferroptosis scores in the TCGA cohort, which was also verified in the E-MTAB-4321 cohort (HR = 4.71, 95% CI: 1.58−14.03, p < 0.0001), the GSE31684 cohort (HR = 1.76, 95% CI: 1.08−2.87, p = 0.02), and the pan-cancer cohort (HR = 1.15, 95% CI: 1.07−1.24, p < 0.0001). Tumor immunity-related pathways, including the IL-17 signaling pathway and JAK-STAT signaling pathway, were found to be associated with the ferroptosis score in BCa through a functional enrichment analysis. Further verification in the IMvigor210 cohort revealed the BCa patients with high ferroptosis scores tended to have worse survival outcome after receiving tumor immunotherapy. Significantly different ferroptosis scores could also be found between BCa patients with different reactions to treatment with immune checkpoint inhibitors.

Identification of RNA-splicing factor Lsm12 as a novel tumor-associated gene and a potent biomarker in Oral Squamous Cell Carcinoma (OSCC).

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the common cancers worldwide. The lack of specific biomarkers and therapeutic targets leads to delayed diagnosis and hence the poor prognosis of OSCC patients. Thus, it is urgent to identify effective biomarkers and therapeutic targets for OSCC. METHODS: We established the golden hamster carcinogenic model of OSCC induced by 7,12-dimethylbenz(a) anthrancene (DMBA) and used mRNA microarrays to detect the differentially expressed genes (DEGs). DEGs were validated in OSCC clinical tissue microarrays using immunohistochemistry method. Whole transcriptome sequencing was performed to obtain an overview of biological functions of Lsm12. PCR assay and sequencing were employed to investigate the alternative splicing of genes regulated by Lsm12. Cell proliferation, colony formation, Transwell migration and invasion assay and in vivo tumor formation assay were performed to investigate the roles of Lsm12 and two transcript variants of USO1 in OSCC cells. RESULTS: Lsm12 was identified to be significantly up-regulated in the animal model of OSCC tumorigenesis, which was validated in the clinical OSCC samples. In the paired normal tissues, Lsm12 staining was negative (91%, 92/101) or weak, while in OSCC tissues, positive rate is 100% and strong staining spread over the whole tissues in 93 (93/101, 92%) cases. Lsm12 overexpression significantly promoted OSCC cell growth, colony formation, migration and invasion abilities, while Lsm12 knockdown showed the opposite trends on these phenotypes and obviously inhibited the tumor formation in vivo. Furthermore, Lsm12 overexpression caused the inclusion of USO1 exon 15 and Lsm12 knockdown induced exon 15 skipping. Exon 15-retained USO1 significantly promoted the malignant phenotypes of OSCC cells when compared with the exon 15-deleted USO1. CONCLUSIONS: We identified Lsm12, a novel tumorigenesis-related gene, as an important regulator involved in OSCC tumorigenesis. Lsm12 is a novel RNA-splicing related gene and can regulate the alternative splicing of USO1 exon 15 which was associated closely with OSCC carcinogenesis. Our findings thus provide that Lsm12 might be a potent biomarker and potential therapeutic target for OSCC.

Recent advances in the development and applications of conjugated polymer dots.

Conjugated polymer dots or semiconducting polymer nanoparticles (Pdots) are nanoparticles prepared based on organic polymers. Pdots have the advantages of lower cost, a simple preparation process, good biocompatibility, excellent stability, and easy modification and regulation. Based on these characteristics, they can not only realize super-resolution imaging of subcellular structure, and the localization of deep tissue lesions, but also interact with various substrates to realize quantitative sensing. Besides the imaging and sensing application, these Pdots can also be used as a targeted therapeutic effective agent to achieve several biotherapy functions. In this review, we will focus on the applications of conjugated polymer dots, including related design and preparation strategies, as well as the current situation and future development of specific applications such as imaging and treatment.

Polymorphic selectivity in crystal nucleation.

Crystal nucleation rates have been measured in the supercooled melts of two richly polymorphic glass-forming liquids: ROY and nifedipine (NIF). ROY or 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile is known for its crystals of red, orange, and yellow colors and many polymorphs of solved structures (12). Of the many polymorphs, ON (orange needles) nucleates the fastest with the runner up (Y04) trailing by a factor of 103 when compared under the same mobility-limited condition, while the other unobserved polymorphs are slower yet by at least 5 orders of magnitude. Similarly, of the six polymorphs of NIF, γ' nucleates the fastest, ß' is slower by a factor of 10, and the rest are slower yet by at least 5 decades. In both systems, the faster-nucleating polymorphs are not built from the lowest-energy conformers, while they tend to have higher energies and lower densities and thus greater similarity to the liquid phase by these measures. The temperature ranges of this study covered the glass transition temperature Tg of each system, and we find no evidence that the nucleation rate is sensitive to the passage of Tg. At the lowest temperatures investigated, the rates of nucleation and growth are proportional to each other, indicating that a similar kinetic barrier controls both processes. The classical nucleation theory provides an accurate description of the observed nucleation rates if the crystal growth rate is used to describe the kinetic barrier for nucleation. The quantitative rates of both nucleation and growth for the competing polymorphs enable prediction of the overall rate of crystallization and its polymorphic outcome.

Cost-Utility Analysis of Once-Weekly Semaglutide, Dulaglutide, and Exenatide for Type 2 Diabetes Patients Receiving Metformin-Based Background Therapy in China.

Introduction: The substantial financial burden associated with type 2 diabetes (T2D) over a lifetime cannot be neglected. Therefore, the objective of this study was to evaluate the pharmacoeconomic value of three once-weekly GLP-1 RAs, namely subcutaneous semaglutide (sc. SEMA), dulaglutide (DULA), and extended-release exenatide (e-r EXEN), in treating patients with T2D that cannot be controlled with metformin-based background therapy, and to find a suitable price reduction for non-cost-effective medications, to provide reasonable recommendations to the administration for adjusting drug prices. Methods: The baseline characteristics of the simulation patient cohort were sourced from a comprehensive meta-analysis synthesizing 453 trials evaluating 21 hypoglycemic agents from nine categories of drugs. The UKPDS OM2 was applied to project the long-term effectiveness and costs from a Chinese health care provider's perspective. After cost-utility analysis, the reasonable price adjustment of non-cost-effective options was explored via binary search. Uncertainty was measured by means of sensitivity analysis. Results: After a 40-year simulation, the sc. SEMA, DULA, and e-r EXEN groups yielded 9.6315, 9.5968, and 9.5895 quality-adjusted life years (QALYs), respectively. In terms of expenditure, the total costs for the sc. SEMA, DULA, and e-r EXEN groups were $42012.47, $24931.27, and $40264.80, respectively. DULA was dominant over e-r EXEN due to the higher QALYs and lower total costs. The ICURs of sc. SEMA vs. DULA and sc. SEMA vs. e-r EXEN were $492994.72/QALY and $41622.69/QALY (ICUR > λ), respectively, indicating that sc. SEMA was not more cost-effective than DULA or e-r EXEN. The INMB and absolute NMB yielded the same conclusions which were robust to one-way, scenario, and probabilistic sensitivity analyses. After several assumptions in the binary search, sc. SEMA and e-r EXEN appear to become cost-effective when their annual costs are decreased by 57.67% and 70.34%, respectively, with DULA as a counterpart. Conclusion: From the cost-utility analysis, DULA appears to be the most cost-effective option among sc. SEMA, DULA, and e-r EXEN for the treatment of patients with T2D receiving metformin-based background therapy. With a 57.67% or 70.34% reduction in cost, sc. SEMA or e-r EXEN, respectively, would become as cost-effective as DULA in China.