Cryopreservation of Human Teeth Using Vitrification method with Cryoprotectant Cocktails and N-acetylcysteine for Banking and Clinical Applications.

Preserving freshly-extracted healthy human teeth offers an optional resource for potential tooth transplantation and cell therapy. This study aimed to assess the impact of vitrification, utilizing a blend of cryoprotectant agents and N-acetylcysteine (NAC), on the cryopreservation of periodontal ligament tissues, and investigate the underlying mechanisms of NAC on the tooth cryopreservation. Periodontal ligament cells were isolated from freshly-extracted healthy human permanent teeth, and cell sheets of PDLCs were fabricated. The samples including cell sheets, freshly-extracted human and rat teeth were cryopreserved with or without NAC for three months. The viability, ROS level, gene expressions and microstructure of PDLCs within cell sheets were assessed. The expression of SOD-2, Caspase3, LC3A/B and Catalase were evaluated through western blotting. Histological assessments of cryopreserved cell sheets and teeth were conducted. PDLCs were isolated from cryopreserved teeth, and their immunophenotype and differentiation ability were evaluated. The data was analyzed using one-way analysis of variance. The vitrification method showed good performance in preserving the viability and differentiation potential of PDLCs. Cryopreservation supplemented with NAC improved the survival rate of PDLCs, enhanced osteogenic differentiation ability, upregulated the expression of SOD-2 and Catalase, and inhibited cell apoptosis. Additionally, mRNA sequencing analysis revealed a significant activation of the PI3K-AKT pathway following cryopreservation via vitrification. Adding a PI3K-AKT activator improved the survival rates of PDLCs post-cryopreservation. The vitrification strategy combining various CPAs and NAC proved to be feasible for tooth cryopreservation. Targeting the PI3K-AKT pathway may improve the efficacy of tooth cryopreservation.

Belimumab in early systemic lupus erythematosus: A propensity score matching analysis.

OBJECTIVE: This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months. METHODS: We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed. RESULTS: Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, p = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, p = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed. CONCLUSIONS: In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.

Health state utility values in patients with Ankylosing Spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic condition that requires lifelong treatment and results in a serious disease burden. Health state utility values (HSUVs) are a valuable tool for quantifying this burden and conducting cost-utility analysis. OBJECTIVE: We conducted a systematic review and meta-analysis to obtain estimates of HSUVs in patients with AS, explored potential sources of heterogeneity, and compared pooled patient HSUVs with population norms. METHOD: We searched PubMed, Embase, Web of science, Cochrane database and Scopus until July, 2023 to obtain eligible studies. The methodological quality of the included studies was assessed using the ROBINS-I checklist. RESULTS: Forty-two publications involving 11,354 participants were included in this systematic review. The most commonly used instrument is the EQ-5D (38 studies). The estimated HSUVs for patients with AS from all available studies was pooled as 0.62 (95% CI 0.59 to 0.65). The pooled mean utility estimates from the random effects meta-analysis for SF-6D, EQ-5D-3L, EQ-5D-5L, and HUI3 were 0.65 (95% CI 0.62,0.68), 0.63 (95% CI 0.59,0.66), 0.60 (95% CI 0.42,0.79), and 0.48 (95% CI 0.43,0.53), respectively. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression based on key subgroups. The pooled estimates of EQ-5D-3L were lower for patients published before 2010, with high disease activity, long duration of disease, and in developed countries. CONCLUSION: Pooled estimates of HSUVs for people with AS were substantially lower than population norms. These estimates provide robust evidence that can inform the economic evaluation of new therapies for individuals with AS.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Correlation between disease activity and patient-reported health-related quality of life in rheumatoid arthritis: a cross-sectional study.

OBJECTIVE: We aimed to provide a comprehensive assessment of health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) of different activities and to evaluate the correlation between clinical activity measures and HRQoL instruments. This research also analysed the extent to which different aspects of HRQoL (physical, psychological and social) were affected. DESIGN: Cross-sectional, observational, non-interventional study. SETTING: The study was conducted at the Department of Rheumatology and Immunology, Qilu Hospital, Shandong University. METHODS: From December 2019 to October 2020, a total of 340 RA patients participated in the survey using convenient sampling. Three generic instruments, EQ-5D-5L,SF-12 and the AQoL-4D, as well as an RA-specific instrument,the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI), were administered to assess patients' HRQoL. The Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) was used by doctors to measure patients' clinical activity. Multivariable linear regression was used to compare patients' HRQoL across different levels of activity. Spearman's correlation was used to assess the correlation between doctor-reported clinical activity and HRQoL. RESULTS: A total of 314 patients with RA participated in this study. The mean score of HAQ-DI was 0.87 (SD: 0.91). Using patients in the clinical remission group as a reference, patients in the moderate and high disease activity groups showed significantly reduced health state utility values and HRQoL scores (all p<0.05). On the contrary, there was an increase in HAQ-DI scores, indicating more impairment (p<0.05). All instruments included in the study tended to differentiate disease activity based on multiple criteria, with scores showing a moderate to strong correlation with RA activity (|rs|=0.50 to 0.65). Among them, the disease-specific instrument had the highest correlation. CONCLUSIONS: RA can have considerable impairment on patients' HRQoL, both in terms of physical and psychosocial functioning. Given the strong correlation between clinical activity and HRQoL scores, and the fact that HRQoL can be an important clinical supplement. The EQ-5D-5L is probably the most appropriate generic measurement instrument for measuring HRQoL in RA patients.

Isolated superior mesenteric artery dissection with concomitant vascular aberrancy: Extremely rare cases and clinical implications.

OBJECTIVE: Vascular aberrancy of superior mesenteric artery (SMA) may contribute to the occurrence of SMA dissection. However, there is no direct evidence to support this hypothesis. Etiology, natural history, classification, and treatment options of ISMAD are still in controversial at some degree. We also review the current understanding of ISMAD based on our results. METHODS: Out of 57 patients, 2 cases of isolated superior mesenteric artery dissection (ISMAD) which concomitant with replaced common hepatic artery with SMA origin, are first reported. RESULTS: Two patients have no any typical etiological factors, such as atherosclerosis, hypertension, long-term smoking, and connective tissue disease. The contrast-enhanced computed tomography and (or) angiography showed concomitant SMA aberrancy. They have 81.2°, 132.7° SMA angle, respectively. After conservative treatment of 4, 6 days, respectively, these 2 patients were discharged smoothly. CONCLUSION: Vascular aberrancy may be a new identified risk factor for ISMAD. Even in ISMAD cases with vascular aberrancy, conservative treatment still can be used as first line therapy.

Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced oesophageal squamous cell carcinoma: a systematic review and economic evaluation.

Background: Recently, several novel programmed cell death protein 1 (PD-1) inhibitors have been approved for second-line treating advanced or metastatic oesophageal squamous cell carcinoma (OSCC), including camrelizumab, nivolumab, pembrolizumab, sintilimab and tislelizumab. However, the optimal treatment regimen remained ambiguous. Objectives: The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective. Design: A systematic review and economic evaluation. Data sources and methods: A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase and Scopus databases to identify eligible studies until 31 August 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS) and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on five clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios for various treatment options. Direct medical costs and utility values were obtained from public drug bidding databases, clinical trials or published literature. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. Results: Five randomized controlled trials involving 2837 patients were included in the analysis. Compared with other treatments examined, camrelizumab provided the best PFS benefits [hazard ratio (HR): 0.69, 95% confidence interval (CI): 0.56-0.86], and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2 and 3 times GDP per capita in 2022, sintilimab, tislelizumab and camrelizumab were the most cost-effective treatment options, respectively. Conclusion: Sintilimab might be the optimal treatment alternative for second-line therapy of advanced OSCC in China, followed by tislelizumab and camrelizumab. Trial registration: This study has been registered on the PROSPERO database with the registration number CRD42023495204.

METHODS: A systematic review was undertaken utilizing PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases to identify eligible studies until August 31, 2023. Primary outcomes were progression-free survival (PFS), overall survival (OS), and adverse events (AEs). We also developed a partitioned survival model at 3-week intervals based on 5 clinical trials to predict long-term costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) for various treatment options. Direct medical costs and utility values were obtained from public drug bidding database, clinical trials or published literatures. The parameter uncertainties within the model were determined via one-way and probabilistic sensitivity analyses. RESULTS: Compared with other treatments examined, camrelizumab provided the best PFS benefits (HR: 0.69, 95% CI: 0.56-0.86), and pembrolizumab provided the best OS benefits (HR: 0.55, 95% CI: 0.37-0.82). Nivolumab caused a relatively lower incidence of treatment-related AEs (HR: 0.10, 95% CI: 0.05-0.20) and grade 3-5 AEs (HR: 0.13, 95% CI: 0.08-0.21) than other immunotherapy regimens. In the economic evaluation, average 10-year costs ranged from $5,433.86 (chemotherapy) to $50,617.95 (nivolumab) and mean QALYs ranged from 0.55 (chemotherapy) to 0.82 (camrelizumab). Pembrolizumab was eliminated because of dominance. Of the remaining strategies, when the willingness-to-pay thresholds were 1, 2, and 3 times GDP per capita in 2022, sintilimab, tislelizumab, and camrelizumab were the most cost-effective treatment options, respectively. CONCLUSION: Sintilimab might be the optimal treatment alternative for second-line therapy of advanced ESCC in China, followed by tislelizumab and camrelizumab.

Immune checkpoint inhibitors versus chemotherapy as second-line therapy for advanced esophageal squamous cell carcinoma: a systematic review and economic evaluation Background: The purpose of this study was to investigate the efficacy, safety and economy of available PD-1 inhibitors to determine the optimal treatment from the Chinese healthcare system perspective.

Characterization of cells in blood evoked from periapical tissues in immature teeth with pulp necrosis and their potential for autologous cell therapy in Regenerative Endodontics.

OBJECTIVE: The objectives of this study were to isolate, characterize progenitor cells from blood in the root canals of necrotic immature permanent teeth evoked from periapical tissues and evaluate the applicable potential of these isolated cells in Regenerative Endodontics. DESIGN: Ten necrotic immature permanent teeth from seven patients were included. Evoked bleeding from periapical tissues was induced after chemical instrumentation of the root canals. Cells were isolated from the canal blood and evaluated for cell surface marker expression, multilineage differentiation potential, proliferation ability, and target protein expression. Cell sheets formed from these cells were transferred into human root segments, and then transplanted into nude mice. Histological examination was performed after eight weeks. Data analysis was conducted using one-way ANOVA followed by Tukey's post-hoc comparison, considering p < 0.05 as statistically significant. RESULTS: The isolated cells exhibited characteristics typical of fibroblastic cells with colony-forming efficiency, and displayed Ki67 positivity and robust proliferation. Flow cytometry data demonstrated that at passage 3, these cells were positive for CD73, CD90, CD105, CD146, and negative for CD34 and CD45. Vimentin expression indicated a mesenchymal origin. Under differentiation media specific differentiation media, the cells demonstrated osteogenic, adipogenic, and chondrogenic differentiation potential. Subcutaneous root canals with cell sheets of isolated cells in nude mice showed the formation of pulp-like tissues. CONCLUSIONS: This study confirmed the presence of progenitor cells in root canals following evoked bleeding from periapical tissues of necrotic immature teeth. Isolated cells exhibited similar immunophenotype and regenerative potential with dental mesenchymal stromal cells in regenerative endodontic therapy.

Health-related quality of life and its changes of the Tibetan population in China: based on the 2013 and 2018 National Health Services Surveys.

OBJECTIVE: Health-related quality of life (HRQoL) was an important health outcome measure for evaluating an individual's overall health status. However, there was limited in the literature on HRQoL and its long-term changes of the Tibetan population. This study aimed to assess HRQoL of Tibetan and its changes over time, and explore the differences in HRQoL for residents at different altitudes. DESIGN: Data for the cross-sectional study were extracted from the fifth and sixth waves of the National Health Services Surveys which were conducted in 2013 and 2018. A multistage stratified cluster random sampling strategy was used to select representative participants. SETTING: Tibet Autonomous Region in China. PARTICIPANTS: This study recruited 14 752 participants in 2013 and 13 106 participants in 2018, and after excluding observations with missing values for key variables, 10 247 in 2013 and 6436 in 2018 were included in the study analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: The EQ-5D-3L was used to measure participants' HRQoL. RESULTS: The mean health state utility scores of the participants were 0.969±0.078 and 0.966±0.077 in 2013 and 2018, respectively. Pain/discomfort was the most frequently prevalent issue reported in 18.1% and 17.9% of the participants in 2013 and 2018, respectively. Tibetans living 3500-4000 m altitude had the best HRQoL. Age, sex, employment status, educational attainment, chronic disease and weekly physical exercise were influencing factors associated with HRQoL. CONCLUSIONS: The HRQoL of the Tibetan population was lower than the general Chinese population, and decreased over time between 5 years. There were differences in HRQoL among Tibetan at different altitudes, with residents living at 3500-4000 m having the best quality of life. More attention should be paid to those Tibetans who are older, female, unemployed and without formal education.

Immune Remodeling during Aging and the Clinical Significance of Immunonutrition in Healthy Aging.

Aging is associated with changes in the immune system and the gut microbiota. Immunosenescence may lead to a low-grade, sterile chronic inflammation in a multifactorial and dynamic way, which plays a critical role in most age-related diseases. Age-related changes in the gut microbiota also shape the immune and inflammatory responses. Nutrition is a determinant of immune function and of the gut microbiota. Immunonutrion has been regarded as a new strategy for disease prevention and management, including many age-related diseases. However, the understanding of the cause-effect relationship is required to be more certain about the role of immunonutrition in supporting the immune homeostasis and its clinical relevance in elderly individuals. Herein, we review the remarkable quantitative and qualitative changes during aging that contribute to immunosenescence, inflammaging and microbial dysbiosis, and the effects on late-life health conditions. Furthermore, we discuss the clinical significance of immunonutrition in the treatment of age-related diseases by systematically reviewing its modulation of the immune system and the gut microbiota to clarify the effect of immunonutrition-based interventions on the healthy aging.

HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.

Hepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian cancer stem cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3'-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC.

Dental Pulp Stem Cell-Derived Exosomes Regulate Anti-Inflammatory and Osteogenesis in Periodontal Ligament Stem Cells and Promote the Repair of Experimental Periodontitis in Rats.

Purpose: Dental pulp stem cell-derived exosomes (DPSC-EXO), which have biological characteristics similar to those of metrocytes, have been found to be closely associated with tissue regeneration. Periodontitis is an immune inflammation and tissue destructive disease caused by plaque, resulting in alveolar bone loss and periodontal epithelial destruction. It is not clear whether DPSC-EXO can be used as an effective therapy for periodontal regeneration. The purpose of this study was not only to verify the effect of DPSC-EXO on reducing periodontitis and promoting periodontal tissue regeneration, but also to reveal the possible mechanism. Methods: DPSC-EXO was isolated by ultracentrifugation. Then it characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA) and Western Blot. In vitro, periodontal ligament stem cells (PDLSCs) were treated with DPSC-EXO, the abilities of cell proliferation, migration and osteogenic potential were evaluated. Furthermore, we detected the expression of IL-1ß, TNF-αand key proteins in the IL-6/JAK2/STAT3 signaling pathway after simulating the inflammatory environment by LPS. In addition, the effect of DPSC-EXO on the polarization phenotype of macrophages was detected. In vivo, the experimental periodontitis in rats was established and treated with DPSC-EXO or PBS. After 4 weeks, the maxillae were collected and detected by micro-CT and histological staining. Results: DPSC-EXO promoted the proliferation, migration and osteogenesis of PDLSCs in vitro. DPSC-EXO also regulated inflammation by inhibiting the IL-6/JAK2/STAT3 signaling pathway during acute inflammatory stress. In addition, the results showed that DPSC-EXO could polarize macrophages from the M1 phenotype to the M2 phenotype. In vivo, we found that DPSC-EXO could effectively reduce alveolar bone loss and promote the healing of the periodontal epithelium in rats with experimental periodontitis. Conclusion: DPSC-EXO plays an important role in inhibiting periodontitis and promoting tissue regeneration. This study provides a promising acellular therapy for periodontitis.

Distribution of potentially toxic elements in soils and sediments in Pearl River Delta, China: Natural versus anthropogenic source discrimination.

Although anthropogenic contamination has been regarded as the most important source of potentially toxic elements (PTEs) in soils of large river delta plains, the extent to which human activities affect PTEs in soils is worth exploring. This study used high density geochemical data to distinguish source patterns of PTEs in soils of the Pearl River Delta Economic Zone, a large industrialized and urbanized area in China. Enrichment factor, discriminant analysis, principal components analysis, cumulative distribution function, and positive matrix factorization were used to identify sources of PTEs in soils. The results indicated that parent material was the most significant factor affecting geochemical characteristics of PTEs in soils. Median concentrations of Cd, Cr, Cu, Hg, Pb, and Zn were 0.400, 88.5, 40.5, 0.143, 43.0, and 116.0 mg/kg for stream sediments, 0.333, 75.7, 39.0, 0.121, 42.6, and 98.5 mg/kg for deep soils, and 0.365, 74.0, 45.1, 0.143, 44.6, and 119.5 mg/kg for surface soils, respectively, all of which exceed relevant reference standards. Compared with stream sediments and deep soils, surface soils exhibit substantial concentrations of PTEs. Chemical weathering and erosion of parent materials distributed in the Pearl River Delta were the main sources of PTEs in soils. Diffuse contamination and many small local contamination sources distributed throughout the study area were the most significant anthropogenic sources of PTEs in surface soils. Intensive human activities failed to change the soil geochemical characteristics derived from the parent material at the regional scale. However, it could induce non-point source pollution and local severe PTEs pollution in surface soils.

Engineered phage with cell-penetrating peptides for intracellular bacterial infections.

IMPORTANCE: Salmonella infection is a significant threat to global public health, and the increasing prevalence of antibiotic resistance exacerbates the situation. Therefore, finding new and effective ways to combat this pathogen is essential. Phages are natural predators of bacteria and can be used as an alternative to antibiotics to kill specific bacteria, including drug-resistant strains. One significant limitation of using phages as antimicrobial agents is their low cellular uptake, which limits their effectiveness against intracellular bacterial infections. Therefore, finding ways to enhance phage uptake is crucial. Our study provides a straightforward strategy for displaying cell-penetrating peptides on non-model phages, offering a promising novel and effective therapeutic approach for treating intracellular and drug-resistant bacteria. This approach has the potential to address the global challenge of antibiotic resistance and improve public health outcomes.

Mapping the Seattle Angina Questionnaire to EQ-5D-5L in patients with coronary heart disease.

BACKGROUND: Health economic evaluation is critical in supporting novel cardiovascular disease therapies. However, most clinical studies do not include preference-based questionnaires to calculate utilities for health economic evaluations. Thus, this study aimed to develop mapping algorithms that convert the Seattle Angina Questionnaire (SAQ) to EQ-5D-5L health utility scores for patients with coronary health disease (CHD) in China. METHODS: Data were obtained from a longitudinal study of patients with CHD conducted at the Tianjin Medical University General Hospital in China. Convenience sampling was used to recruit patients with CHD. The inclusion criteria were having been diagnosed with CHD through a medical examination and being aged 18 years or older. The exclusion criteria were a lack of comprehension ability, serious comorbidities, mental illness, and hearing or vision impairment. All eligible patients were invited to participate, and 305 and 75 patients participated at baseline and in the follow-up, respectively. Seven regression models were developed using a direct approach. Furthermore, we predicted the five EQ-5D items using ordered logit model and derived the utility score from predicted responses using an indirect approach. Model performances were evaluated using mean absolute error (MAE), root mean squared error (RMSE), correlation coefficient (ρ), and Lin's concordance correlation coefficient (CCC). A five-fold cross-validation method was used to evaluate internal validation. RESULTS: The average age was 63.04 years, and 53.72% of the included patients were male. Most (70.05%) patients had unstable angina pectoris, and the mean illness duration was 2.50 years. The EQ-5D scores were highly correlated with five subscales of the SAQ, with Spearman's rank correlation coefficients ranging from 0.6184 to 0.7093. The mixture beta model outperformed the other regression models in the direct approach, with the lowest MAE and RMSE and highest ρ and CCC. The ordered logit model in the indirect approach performed the same as the mixture beta regression with equal MAE, lower RMSE, and higher ρ and CCC. CONCLUSION: Mapping algorithms developed using mixture beta and ordered logit models accurately converted SAQ scores to EQ-5D-5L health utility values, which could support health economic evaluations related to coronary heart disease.

Psychometric properties and comparison of four health utility approaches among myopia patients in China.

BACKGROUND: The increased prevalence of myopia creates and earlier age of onset has created public health concerns for the long-term eye health, vision impairment and carries with it a significant economic burden. The quality of the economic evaluation is dependent on the sensitivity and validity of the approaches. Nowadays, there are many approaches to measure patients' health state utility (HSU). However, little is known regarding the performance of direct approach and indirect approach in people with myopia. This study is aimed to compare the psychometric properties of four HSU approaches among patients with myopia in mainland China, including two direct approaches (TTO and SG), the generic preference-based measures (PBM) (AQoL-7D) and the disease-specific PBM (VFQ-UI). METHODS: A convenience sampling framework was used to recruit patients with myopia who attended a large ophthalmic hospital in Jinan, China. Spearman's rank correlations coefficient was used to assess concurrent validity. Known-group validity was analyzed by: (1) whether the patients wear corrective devices; (2) severity of myopia as low or moderate to high of the better eye; (3) duration of myopia as ≤ 10 years or > 10 years. Effect size (ES), relative efficiency (RE) statistic and the largest area under the receiver operating characteristic curve (AUC) were used to assess sensitivity. The intra-class correlation coefficient (ICC) and Bland-Altman plots were used to assess agreement. RESULTS: A valid sample size of 477 myopia patients was analyzed (median duration: 10 years). The mean HSU scores between TTO and SG were similar (0.95) and higher than AQoL-7D (0.89) and VFQ-UI (0.83). Overall, the VFQ-UI had the best performance based on the psychometric analysis. The agreement indicated that there was no pair of approaches that could be used interchangeably. CONCLUSIONS: The VFQ-UI showed better psychometric properties than other three approaches for providing health state utility in Chinese myopia patients. Given the widespread use and its generic nature of the AQoL-7D, it could be used alongside with VFQ-UI to provide complementary health state utility from a generic and disease-specific perspective for economic evaluation. More evidence on the responsiveness of four health utility approaches in myopia patients is required.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

AIM: To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). METHODS: This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. RESULTS: A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. CONCLUSION: The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

Adrenomedullin induces cisplatin chemoresistance in ovarian cancer through reprogramming of glucose metabolism.

Background and Objectives: The metabolic network of cancer cells has been reprogrammed - relying more on aerobic glycolysis to gain energy, which is an important reason for drug resistance. Expression of adrenomedullin (ADM) in ovarian cancer tissues is related to resistance to platinum-based drugs. In view of this, we intended to investigate the correlation between ADM and glucose metabolism reprogramming of tumor cells to clarify the possible mechanism of ADM-induced ovarian cancer cisplatin resistance through glucose metabolism reprogramming. Methods: Epithelial ovarian cancer (EOC) cell viability and apoptosis were determined. Different gene expression and protein levels were detected by real-time revere transcription polymerase chain reaction and western blotting. Oxygen consumption rate (OCR) and extracellular acidification rates (ECARs) were measured. Results: ADM expression was upregulated in cisplatin-resistant EOC cells. ADM attenuated cisplatin-inhibited cell survival and cisplatin-induced apoptosis in sensitive EOC cells; knockdown of ADM enhanced cisplatin chemosensitivity of cisplatin-resistant EOC cells. ADM enhanced glycolysis in cisplatin-sensitive EOC cells; knockdown of ADM significantly inhibited glycolysis in cisplatin-resistant EOC cells. ADM significantly upregulated pyruvate kinase isozyme type M2 (PKM2) protein level, the key enzyme during glycolysis; PKM2 inhibitor significantly abolished the ADM-improved cell survival and ADM-inhibited apoptosis. Conclusion: ADM promoted proliferation and inhibited apoptosis of ovarian cancer cells through reprogramming of glucose metabolism, so as to promote cisplatin resistance. The study is expected to identify multidrug resistance markers of ovarian cancer and provide a target for the prevention and treatment of ovarian cancer, which is important for clinical translational research.

Cost-effectiveness analysis of serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive esophageal squamous cell carcinoma in China.

Objective: The ASTRUM-007 trial (NCT03958890) demonstrated that serplulimab plus chemotherapy administered every 2-week significantly improved progression-free and overall survival in patients with previously untreated, programmed death-ligand 1 (PD-L1) positive advanced esophageal squamous-cell carcinoma (ESCC). This study was aimed to investigate the cost-effectiveness of serplulimab plus chemotherapy in the first-line treatment of PD-L1-positive advanced ESCC. Methods: A partitioned survival model with a 2-week cycle and a 10-year time horizon was constructed from the Chinese healthcare system perspective. The survival data, direct medical costs and utilities were derived from the ASTRUM-007 trial, YAOZHI database and published sources. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with chemotherapy, serplulimab plus chemotherapy provided additional 0.27 QALYs with an incremental cost of $33,460.86, which had an ICER of $124,483.07 per QALY. The subgroup analyses revealed that the ICERs of serplulimab plus chemotherapy were $134,637.42 and $105,589.71 in advanced ESCC patients with 1 ≤ CPS < 10 and CPS ≥ 10, respectively. The price of serplulimab, patient weight, utility values and discount rate were the most influential parameters on base-case results. At a willingness-to-pay threshold of three times per capita GDP ($40,587.59) in 2022, the probability of serplulimab plus chemotherapy being cost-effective was 0% compared with chemotherapy. When the price of serplulimab decreased by 70%, the probabilities of serplulimab plus chemotherapy being cost-effective were 81.42%, 67.74% and 96.75% in advanced ESCC patients with PD-L1-positive, PD-L1 1≤CPS<10 and CPS≥10, respectively. Conclusion: Serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive advanced ESCC might not be cost-effective in China.