DataSheet_1_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.docx

ObjectiveThe 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.MethodsFrom 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.ResultsIn 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$30,036/QALY.ConclusionCompared with regorafenib, serplulimab is a cost-effective treatment for patients with previously treated unresectable or metastatic MSI-H/dMMR colorectal cancer in China.</p

Arsenate Adsorption by Hydrous Ferric Oxide Nanoparticles Embedded in Cross-linked Anion Exchanger: Effect of the Host Pore Structure

Three composite adsorbents were fabricated via confined growth of hydrous ferric oxide (HFO) nanoparticles within cross-linked anion exchangers (NS) of different pore size distributions to investigate the effect of host pore structure on the adsorption of As­(V). With the decrease in the average pore size of the NS hosts from 38.7 to 9.2 nm, the mean diameter of the confined HFO nanoparticles was lessened from 31.4 to 11.6 nm as observed by transmission electron microscopy (TEM), while the density of active surface sites was increased due to size-dependent effect proved by potentiometric titration. The adsorption capacity of As­(V) yielded by Sips model was elevated from 24.2 to 31.6 mg/g via tailoring the pore size of the NS hosts, and the adsorption kinetics was slightly accelerated with the decrease of pore size in background solution containing 500 mg/L of Cl^–. Furthermore, the enhanced adsorption of As­(V) was achieved over a wide pH range from 3 to 10, as well as in the presence of competing anions including Cl^–, SO₄^2–, HCO₃^–, NO₃^– (up to 800 mg/L), and PO₄^3– (up to 10 mg P/L). In addition, the fixed-bed working capacity increased from 2200 to 2950 bed volumes (BV) owing to the size confinement effect, which did not have adverse effect on the desorption of As­(V) as the cumulative desorption efficiency reached 94% with 10 BV of binary solution (5% NaOH + 5% NaCl) for all the three adsorbents. Therefore, this study provided a promising strategy to regulate the reactivity of the nanoparticles via the size confinement effect of the host pore structure

Table_1_The efficacy and safety of eravacycline compared with current clinically common antibiotics in the treatment of adults with complicated intra-abdominal infections: A Bayesian network meta-analysis.DOCX

BackgroundEravacycline is a novel, fully synthetic fluorocycline antibiotic for the treatment of adults with complicated intra-abdominal infections (cIAIs). However, the efficacy and safety of eravacycline compared with current clinically common antibiotics remain unknown.ObjectiveThis study aims to compare the efficacy and safety of eravacycline and other clinically common antibiotics in China, including tigecycline, meropenem, ertapenem, ceftazidime/avibactam+metronidazole, piperacillin/tazobactam, imipenem/cilastatin, and ceftriaxone+metronidazole, for the treatment of adults with cIAIs and to provide a reference for clinical choice.MethodsThe PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were electronically searched to collect clinical randomized controlled studies (RCTs) comparing different antibiotics in the treatment of patients with cIAIs from inception to June 1, 2021. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies.ResultsA total of 4050 articles were initially retrieved, and 25 RCTs were included after screening, involving eight treatment therapies and 9372 patients. The results of network meta-analysis showed that in the intention-to-treat (ITT) population, the clinically evaluable (CE) population, and the microbiologically evaluable (ME) population, the clinical response rate of eravacycline was not significantly different from that of the other 7 therapies (P > 0.05). In terms of microbiological response rate, eravacycline was significantly better than tigecycline [tigecycline vs. eravacycline: RR = 0.82, 95%CI (0.65,0.99)], and there was no significant difference between the other 6 regimens and eravacycline (P > 0.05). In terms of safety, the incidence of serious adverse events, discontinuation rate, and all-cause mortality of eravacycline were not significantly different from those of the other 7 treatment therapies (P > 0.05).ConclusionBased on the evidence generated by the current noninferiority clinical trial design, the efficacy and safety of eravacycline for the treatment of adults with cIAIs are not significantly different from those of the other 7 commonly used clinical antibiotics in China. In terms of microbiological response rate, eravacycline was significantly better than tigecycline. In view of the severe multidrug-resistant situation in China, existing drugs have difficulty meeting the needs of clinical treatment, and the new antibacterial drug eravacycline may be one of the preferred options for the treatment of cIAIs in adults.</p

Additional file 1: of Item reduction and validation of the Chinese version of diabetes quality-of-life measure (DQOL)

Original Chinese DQOL and short versions based on the CTT and IRT. (DOCX 29 kb

Supplementary Video S1 for: Therapeutic potential of human adipose-derived stem cell exosomes in stress urinary incontinence – an in vitro and in vivo study

<a>The video showed the Brownian activity of the hADSCs-derived exosome particles.</a><br><p><a><b>Background/Aims: </b></a>To evaluate whether local injection of exosomes derived from human adipose-derived stem cells (hADSCs) facilitates recovery of stress urinary incontinence (SUI) in a rat model.</p> <p><b>Methods:</b> For the in vitro study, a Cell Counting Kit-8 (CCK-8) array and proteomic analysis were performed. For the in vivo study, female rats were divided into four groups: sham, SUI, adipose-derived stem cell (ADSC), and exosomes (<i>n</i> = 12 each). The SUI model was generated by pudendal nerve transection and vaginal dilation. Vehicle, hADSCs, or exosomes were injected into the peripheral urethra. After 2, 4, and 8 weeks, the rats underwent cystometrography and leak point pressure (LPP) testing, and tissues were harvested for histochemical analyses.</p> <p><b>Results:</b> The CCK-8 experiment demonstrated that ADSC-derived exosomes could enhance the growth of skeletal muscle and Schwann cell lines in a dose-dependent manner. Proteomic analysis revealed that ADSC-derived exosomes contained various proteins of different signaling pathways. Some of these proteins are associated with the PI3K-Akt, Jak-STAT, and Wnt pathways, which are related to skeletal muscle and nerve regeneration and proliferation. In vivo experiments illustrated that rats of the exosome group had higher bladder capacity and LPP, and had more striated muscle fibers and peripheral nerve fibers in the urethra than rats of the SUI group. Both urethral function and histology of rats in the exosome group were slightly better than those in the ADSC group. </p> <b>Conclusions:</b> Local injection of hADSC-derived exosomes improved functional and histological recovery after SUI

Supplementary Table S1 for: Therapeutic potential of human adipose-derived stem cell exosomes in stress urinary incontinence – an in vitro and in vivo study

Results of GO analysis<p><a><b>Background/Aims: </b></a>To evaluate whether local injection of exosomes derived from human adipose-derived stem cells (hADSCs) facilitates recovery of stress urinary incontinence (SUI) in a rat model.</p> <p><b>Methods:</b> For the in vitro study, a Cell Counting Kit-8 (CCK-8) array and proteomic analysis were performed. For the in vivo study, female rats were divided into four groups: sham, SUI, adipose-derived stem cell (ADSC), and exosomes (<i>n</i> = 12 each). The SUI model was generated by pudendal nerve transection and vaginal dilation. Vehicle, hADSCs, or exosomes were injected into the peripheral urethra. After 2, 4, and 8 weeks, the rats underwent cystometrography and leak point pressure (LPP) testing, and tissues were harvested for histochemical analyses.</p> <p><b>Results:</b> The CCK-8 experiment demonstrated that ADSC-derived exosomes could enhance the growth of skeletal muscle and Schwann cell lines in a dose-dependent manner. Proteomic analysis revealed that ADSC-derived exosomes contained various proteins of different signaling pathways. Some of these proteins are associated with the PI3K-Akt, Jak-STAT, and Wnt pathways, which are related to skeletal muscle and nerve regeneration and proliferation. In vivo experiments illustrated that rats of the exosome group had higher bladder capacity and LPP, and had more striated muscle fibers and peripheral nerve fibers in the urethra than rats of the SUI group. Both urethral function and histology of rats in the exosome group were slightly better than those in the ADSC group. </p> <b>Conclusions:</b> Local injection of hADSC-derived exosomes improved functional and histological recovery after SUI

Supplementary Figure S1 for: Therapeutic potential of human adipose-derived stem cell exosomes in stress urinary incontinence – an in vitro and in vivo study

HE staining of mid-urethra 8 weeks after injection showed no detectable increase in inflammatory cells around the injection site in the ADSC and exosome groups compared with sham. The results indicated that no significant immune response was induced.<p><a><b>Background/Aims: </b></a>To evaluate whether local injection of exosomes derived from human adipose-derived stem cells (hADSCs) facilitates recovery of stress urinary incontinence (SUI) in a rat model.</p> <p><b>Methods:</b> For the in vitro study, a Cell Counting Kit-8 (CCK-8) array and proteomic analysis were performed. For the in vivo study, female rats were divided into four groups: sham, SUI, adipose-derived stem cell (ADSC), and exosomes (<i>n</i> = 12 each). The SUI model was generated by pudendal nerve transection and vaginal dilation. Vehicle, hADSCs, or exosomes were injected into the peripheral urethra. After 2, 4, and 8 weeks, the rats underwent cystometrography and leak point pressure (LPP) testing, and tissues were harvested for histochemical analyses.</p> <p><b>Results:</b> The CCK-8 experiment demonstrated that ADSC-derived exosomes could enhance the growth of skeletal muscle and Schwann cell lines in a dose-dependent manner. Proteomic analysis revealed that ADSC-derived exosomes contained various proteins of different signaling pathways. Some of these proteins are associated with the PI3K-Akt, Jak-STAT, and Wnt pathways, which are related to skeletal muscle and nerve regeneration and proliferation. In vivo experiments illustrated that rats of the exosome group had higher bladder capacity and LPP, and had more striated muscle fibers and peripheral nerve fibers in the urethra than rats of the SUI group. Both urethral function and histology of rats in the exosome group were slightly better than those in the ADSC group. </p> <b>Conclusions:</b> Local injection of hADSC-derived exosomes improved functional and histological recovery after SUI