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Mutations in PRPH2 are a relatively common cause of sight-robbing inherited retinal degenerations (IRDs). Peripherin-2 (PRPH2) is a photoreceptor-specific tetraspanin protein that structures the disk rim membranes of rod and cone outer segment (OS) organelles, and is required for OS morphogenesis. PRPH2 is noteworthy for its broad spectrum of disease phenotypes; both inter- and intra-familial heterogeneity have been widely observed and this variability in disease expression and penetrance confounds efforts to understand genotype-phenotype correlations and pathophysiology. Here we report the generation and initial characterization of a gene-edited animal model for PRPH2 disease associated with a nonsense mutation (c.1095:C>A, p.Y285X), which is predicted to truncate the peripherin-2 C-terminal domain. Young (P21) Prph2Y285X/WT mice developed near-normal photoreceptor numbers; however, OS membrane architecture was disrupted, OS protein levels were reduced, and in vivo and ex vivo electroretinography (ERG) analyses found that rod and cone photoreceptor function were each severely reduced. Interestingly, ERG studies also revealed that rod-mediated downstream signaling (b-waves) were functionally compensated in the young animals. This resiliency in retinal function was retained at P90, by which time substantial IRD-related photoreceptor loss had occurred. Altogether, the current studies validate a new mouse model for investigating PRPH2 disease pathophysiology, and demonstrate that rod and cone photoreceptor function and structure are each directly and substantially impaired by the Y285X mutation. They also reveal that Prph2 mutations can induce a functional compensation that resembles homeostatic plasticity, which can stabilize rod-derived signaling, and potentially dampen retinal dysfunction during some PRPH2-associated IRDs., (© The Author(s) 2024. Published by Oxford University Press.)

Lymphangiogenesis is a precursor to lymphovascular invasion, and may therefore signal a higher risk of metastasis and mortality in primary cutaneous melanoma. This retrospective longitudinal study aimed to evaluate whether emergent lymphangiogenesis, as measured through co-expression of endothelial proteins with the proliferation marker Ki67, was associated with poorer prognosis in a cohort of patients with single primary cutaneous melanoma. We screened all patients with a single locally invasive primary cutaneous melanoma who received sentinel lymph node biopsy at a tertiary dermatology centre in Brisbane, Australia between 1994 and 2007. Primary melanoma sections were stained via Opal multiplex immunofluorescence, and categorized according to the presence of Ki67 within either CD31 + or D2-40 + endothelial cells. Multivariate Cox regression modelling was used to evaluate associations between endothelial Ki67 positivity and clinical outcomes, with adjustment for age, sex, Breslow depth, ulceration, and anatomical location. Overall, 264 patients were available for analysis, with a median follow-up duration of 7.1 years. The presence of D2-40 + /Ki67 + co-expression was associated with greater melanoma-specific mortality (adjusted hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.33-3.10; p = 0.001) and recurrence (adjusted HR: 1.70; 95% CI: 1.33-3.10; p = 0.001) relative to absence. CD31 + /Ki67 + co-expression was not prognostic in this cohort. Lymphatic proliferation, as measured through D2-40 + /Ki67 + co-expression, predicted greater melanoma-specific mortality and recurrence in this cohort of primary cutaneous melanoma., (© 2024 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest Dr Soyer is a shareholder of MoleMap NZ Limited and e-derm consult GmbH and undertakes regular teledermatological reporting for both companies; is a medical consultant for Canfield Scientific Inc, MoleMap Australia Pty Ltd, Blaze Bioscience Inc; and a medical advisor for First Derm. Dr Rimm has served as an advisor for Astra Zeneca, Amgen, Cell Signaling Technology, Cepheid, Danaher, Daiichi Sankyo, Konica Minolta, Merck, NanoString, PAIGE.AI, Regeneron, and Sanofi. Drs Tan, Aung, Claeson, Acs, Zhou; Author Brown; and Drs Lambie, Baade, Pandeya, Smithers, Whiteman, and Khosrotehrani have no conflicts of interest to declare.

Identifying prognostic biomarkers to predict clinical outcomes in stage I and II cutaneous melanomas could guide the clinical application of adjuvant and neoadjuvant therapies. We aimed to investigate the prognostic value of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) as a biomarker in early-stage melanoma. This study evaluated all initially staged Ib and II melanoma patients undergoing sentinel node biopsy at a tertiary centre in Brisbane, Australia between 1994 and 2007, with survival data collected from the Queensland Cancer Registry. Primary melanoma tissue from 189 patients was analysed for pSTAT5 level through immunohistochemistry. Cox regression modelling, with adjustment for sex, age, ulceration, anatomical location, and Breslow depth, was applied to determine the association between pSTAT5 detection and melanoma-specific survival. Median duration of follow-up was 7.4 years. High pSTAT5 detection was associated with ulceration and increased tumour thickness. However, multivariate analysis indicated that high pSTAT5 detection was associated with improved melanoma-specific survival (hazard ratio: 0.15, 95% confidence interval: 0.03-0.67) as compared to low pSTAT5 detection. This association persisted when pSTAT5 detection was limited to immune infiltrate or the vasculature, as well as when sentinel node positivity was accounted for. In this cohort, staining for high-pSTAT5 tumours identified a subset of melanoma patients with increased survival outcomes as compared to low-pSTAT5 tumours, despite the former having higher-risk clinicopathological characteristics at diagnosis. pSTAT5 is likely an indicator of local immune activation, and its detection could represent a useful tool to stratify the risk of melanoma progression., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Antiobesity pharmacotherapy is recommended for adolescents ages 12 years and older with obesity. Several medications have been approved by the US Food and Drug Administration for adolescent use, but the most cost-effective medication remains unclear., Objective: To estimate the cost-effectiveness of lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate (7.5 mg phentermine and 46 mg topiramate), top-dose phentermine and topiramate (15 mg phentermine and 92 mg topiramate), or semaglutide among adolescent patients with obesity., Design, Setting, and Participants: This economic evaluation used a microsimulation model to project health and cost outcomes of lifestyle counseling alone and adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide over 13 months, 2 years, and 5 years among a hypothetical cohort of 100 000 adolescents with obesity, defined as an initial body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 37. Model inputs were derived from clinical trials, published literature, and national sources. Data were analyzed from April 2022 to July 2023., Exposures: Lifestyle counseling alone and as adjunct to liraglutide, mid-dose phentermine and topiramate, top-dose phentermine and topiramate, or semaglutide., Main Outcomes and Measures: The main outcome was quality-adjusted life years (QALYs), costs (2022 US dollars), and incremental cost-effectiveness ratios (ICERs), with future costs and QALYs discounted 3.0% annually. A strategy was considered cost-effective if the ICER was less than $100 000 per QALY gained. The preferred strategy was determined as the strategy with the greatest increase in QALYs while being cost-effective. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty., Results: The model simulated 100 000 adolescents at age 15 with an initial BMI of 37, of whom 58 000 (58%) were female. At 13 months and 2 years, lifestyle counseling was estimated to be the preferred strategy. At 5 years, top-dose phentermine and topiramate was projected to be the preferred strategy with an ICER of $56 876 per QALY gained vs lifestyle counseling. Semaglutide was projected to yield the most QALYs, but with an unfavorable ICER of $1.1 million per QALY gained compared with top-dose phentermine and topiramate. Model results were most sensitive to utility of weight reduction and weight loss of lifestyle counseling and top-dose phentermine and topiramate., Conclusions and Relevance: In this economic evaluation of pharmacotherapy for adolescents with obesity, top-dose phentermine and topiramate as adjunct to lifestyle counseling was estimated to be cost-effective after 5 years. Long-term clinical trials in adolescents are needed to fully evaluate the outcomes of pharmacotherapy, especially into adulthood.

Return to Work (RTW) programmes have become imperative in manpower scarce countries. This paper describes a RTW programme in a Singapore tertiary hospital, reports patient outcomes and discusses the practicality and effectiveness of the programme. Seventy-three workers participated in the programme over a two-year period. A statistically significant increase in work ability and self-perceived overall health status from first contact with worker (baseline) to discharge was observed. Continued programme participation till first RTW was associated with higher work ability and self-perceived overall health status at baseline. The RTW Coordinator-anchored multidisciplinary model which provided holistic support to the worker and addressed stakeholder interests were central to the programme's success. Greater awareness of RTW programme benefits will improve sustained participation. Our RTW programme features, implementation experiences and participant reported effectiveness may inform the development of improved return to work models.

Iridium electrocatalysts have been extensively studied for the acidic water oxidation reaction (2H 2 O → O 2 + 4H + + 4 e - , also known as the oxygen evolution reaction, OER) in recent years. However, the activity of different iridium catalysts, such as amorphous, crystalline, and metallic ones, varies significantly, and there is no common explanation for the origin of this difference. Here four types of iridium catalysts were selected as models and characterized by various techniques. The redox behavior of iridium catalysts and oxidation of hydrogen peroxide (in the form of OOH - ) were applied to in situ probe the adsorption energy of oxygen reaction intermediates (*OH, *O, and *OOH) on iridium catalysts under the OER conditions. Structure-activity analysis suggested that the more optimal and broader distribution of adsorption energies on metallic iridium (iridium black) and its good conductivity are the origin of its highest activity among the four different iridium catalysts.

Introduction: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD., Methods: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC., Results: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40)., Discussion: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Colon cancer incidence is rising in low- and middle-income countries (LMICs), where resource limitations and cost often dictate treatment decisions. In this study, we evaluate the cost-effectiveness of adjuvant chemotherapy for high-risk stage II and stage III colon cancer treatment in South Africa (ZA) and illustrate how such analyses can inform cancer treatment recommendations in a LMIC., Methods: We created a decision-analytic Markov model to compare lifetime costs and outcomes for patients with high-risk stage II and stage III colon cancer treated with three adjuvant chemotherapy regimens in a public hospital in ZA: capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, and capecitabine for 6 months, compared to no adjuvant treatment. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life-year (DALY) averted, at a willingness-to-pay (WTP) threshold equal to the 2021 ZA gross domestic product per capita (I$13,764/DALY averted)., Results: CAPOX for 3 months was cost-effective for both patients with high-risk stage II and patients with stage III colon cancer (ICER = I$250/DALY averted and I$1042/DALY averted, respectively), compared to no adjuvant chemotherapy. In subgroup analyses of patients by tumor stage and number of positive lymph nodes, for patients with high-risk stage II colon cancer and T4 tumors, and patients with stage III colon cancer with T4 or N2 disease. CAPOX for 6 months was cost-effective and the optimal strategy. The optimal strategy in other settings will vary by local WTP thresholds. Decision analytic tools can be used to identify cost-effective cancer treatment strategies in resource-constrained settings., Conclusion: Colon cancer incidence is increasing in low- and middle-income countries, including South Africa, where resource constraints can impact treatment decisions. This cost-effectiveness study evaluates three systemic adjuvant chemotherapy options, compared to surgery alone, for patients in South African public hospitals after surgical resection for high-risk stage II and stage III colon cancer. Doublet adjuvant chemotherapy (capecitabine and oxaliplatin) for 3 months is the cost-effective strategy and should be recommended in South Africa., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Immune checkpoint inhibitors (ICIs) have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer. However, the inhibitors also cause immune-related adverse events (irAEs). The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs., Aim: To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer., Methods: This systematic review was registered with PROSPERO (Reg. number: CRD42020152291). Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs. A systematic literature search was conducted using the PubMed, EMBASE, and Cochrane Library databases. Meta-analysis was carried out using the single sample rate method. Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software., Results: The patients enrolled in the present study included 14 patients from 14 case reports, 326 patients from 6 case series, and 1249 patients from 8 clinical trials. It was found that the overall incidence of irAEs was 16% [95% confidence interval (CI): 11-20] for all grades and 3% (95%CI: 2-4) for the severe grade. It was evident that the incidence of irAEs varied with the type of inhibitor and organs. A comparative study of the anti-programmed cell death receptor-1 (PD-1) and anti-programmed death receptor-ligand 1 (PD-L1) treatments showed that the anti-PD-1 group had a higher overall incidence of irAEs (20%) as compared with that of the anti-PD-L1 group (13%). Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs (7.4%), including hypothyroidism, hyperthyroidism, thyroiditis, diabetes, and adrenal insufficiency, followed by gastroenterology (2.2%), pulmonology (1.8%), neurology (1.4%), dermatology (1.4%), hematology (0.8%), and hepatology (0.7%). In clinical trials, it was found that the incidence of death related to irAEs was 1% (95%CI: 0-2.0), whereby colitis and interstitial lung diseases were the leading causes of death., Conclusion: It was evident that the incidence and nature of irAEs are both organ- and inhibitor-specific. The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs. Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The main objective of the study was to translate, validate, and compare the Chinese ORTO scales (ORTO-15 and ORTO-R). The secondary objective was to assess factors that may be related with risk of orthorexia nervosa (ON)., Methods: Two cross-sectional surveys were conducted on March-to-June 2021 for ORTO-15 and April 2022 for ORTO-R. ORTO questionnaires were translated into Chinese using the forward-backward-forward method. Exploratory factor analysis (EFA), discriminant validity and confirmatory factor analysis (CFA) were used to examine the construct validity of the questionnaires. The internal consistency was assessed using the Cronbach alpha coefficient and the test-retest reliability. Multivariate linear regression analysis was used to explore potential factors related with ON scores., Results: Totally, 1289 and 1084 eligible participants were included for assessment of ORTO-15 and ORTO-R, with the mean age of 20.9 ± 2.0 years and 21.0 ± 2.3 years. The internal consistency of Chinese ORTO-15 scale and ORTO-R scale were both satisfactory (α = 0.79, ICC = 0.79; α = 0.77, ICC = 0.82). However, all ORTO-15 models showed a poor fit using CFA whereas the ORTO-R was characterized by acceptable goodness-of-fit. Multivariate linear regression indicated that physical activities and mental disorders were positively associated with ON risk assessed by both ORTO-R and ORTO-15., Conclusion: The Chinese ORTO-R scale was a more reliable tool to screen for ON tendencies than the Chinese version of ORTO-15. Mental disorders and physical activities might be associated with the increased ON risk., Level of Evidence: Level V (descriptive cross-sectional study)., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background and Aims: Guidelines cite extensive gastric intestinal metaplasia (GIM) as a bigger risk factor for gastric cancer (GC) than limited GIM and an indication for endoscopic surveillance. Data on progression of extensive GIM to GC in the USA are limited. This study aimed to estimate the prevalence and progression rates of extensive GIM in a US cohort., Methods: This retrospective study assessed the prevalence of extensive GIM between 1/1/1990 and 8/1/2019 at a large academic medical center. Multivariable regression was used to identify predictors of extensive GIM. Incidence of GC on follow-up was calculated as number of new diagnoses divided by person-years of follow-up. Presence of GIM on subsequent follow-up endoscopy was assessed., Results: Of 1256 individuals with GIM, 352 (28%) had extensive GIM and 904 (72%) had limited GIM. On multivariable analysis, older age (OR 1.01, 95% CI 1.00-1.02) and Hispanic ethnicity (OR 1.55, 95% CI 1.11-2.16) were predictive of extensive GIM. The annual incidence of GC for GIM overall was 0.09%. There was no difference in progression to GC between extensive or limited GIM (IRR 0, 95% CI 0-2.6), or to advanced lesions overall (IRR 0.37, 95% CI 0.04-1.62). 70% of individuals had persistent GIM on follow-up biopsy, and 22% with limited GIM had extensive GIM on follow-up biopsy., Conclusions: 28% of individuals with GIM have the extensive subtype, and are more likely to be older and of Hispanic ethnicity. There was no difference in progression to GC between extensive and limited GIM. Further research is needed to better assess risk of GIM in the US context., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Guidelines suggest endoscopic screening for esophageal adenocarcinoma (EAC) among individuals with symptoms of gastroesophageal reflux disease (GERD) and additional risk factors. We aimed to determine at what age to perform screening and whether sex and race should influence the decision., Methods: We conducted comparative cost-effectiveness analyses using 3 independent simulation models. For each combination of sex and race (White/Black, 100,000 individuals each), we considered 41 screening strategies, including one-time or repeated screening. The optimal strategy was that with the highest effectiveness and an incremental cost-effectiveness ratio <$100,000 per quality-adjusted life-year gained., Results: Among White men, 536 EAC deaths were projected without screening, and screening individuals with GERD twice at ages 45 and 60 years was optimal. Screening the entire White male population once at age 55 years was optimal in 26% of probabilistic sensitivity analysis runs. Black men had fewer EAC deaths without screening (n = 84), and screening those with GERD once at age 55 years was optimal. Although White women had slightly more EAC deaths (n = 103) than Black men, the optimal strategy was no screening, although screening those with GERD once at age 55 years was optimal in 29% of probabilistic sensitivity analysis runs. Black women had a very low burden of EAC deaths (n = 29), and no screening was optimal, as benefits were very small and some strategies caused net harm., Conclusions: The optimal strategy for screening differs by race and sex. White men with GERD symptoms can potentially be screened more intensely than is recommended currently. Screening women is not cost-effective and may cause net harm for Black women., (Published by Elsevier Inc.)

RNA-guided RNA-targeting nucleases, such as CRISPR-Cas13 proteins, have therapeutic potential for gene editing. Among Cas13d enzymes, Cas13d from the bacteria Ruminococcus flavefaciens (RfxCas13d) is of particular interest owing to its small size and high specificity. However, the existence of pre-existing immunity against RfxCas13d is unclear. In this study, we evaluated antibody and T cell responses to RfxCas13d in healthy donors using ELISA and T cell culture assays. We found RfxCas13d-reactive antibodies and CD4 and CD8 T cell responses in most donors, comparable to responses against Cas9 proteins from Staphylococcus aureus (SaCas9) and Streptococcus pyogenes (SpCas9). RfxCas13d-responding T cells could produce the inflammatory cytokines IFN-γ, TNF-α and IL-17. These findings should be taken into consideration in the development of RfxCas13d for therapy., (© 2022. The Author(s).)

Objectives: To quantify the burden and variation trends of cancers in children under 5 years at the global, regional, and national levels from 1990 to 2019., Methods: Epidemiological data for children under 5 years who were diagnosed with any one childhood cancer were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) from 1990 to 2019. The outcomes were the absolute numbers and rates of incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for different types of cancer., Results: In 2019, 8,774,979.1 incident cases (95% uncertainty interval [UI]: 6,243,599.2 to11,737,568.5) and 8,956,583.8 (6,446,323.9 to 12,364,520.8) prevalent cases of cancer in children under 5 years were identified worldwide; these cancers resulted in 44,451.6 (36,198.7 to 53,905.9) deaths and 3,918,014.8 (3,196,454.9 to 4,751,304.2) DALYs. From 1990 to 2019, although the numbers of incident and prevalent cases only decreased by -4.6% (-7.0 to -2.2) and -8.3% (-12.6 to -3.4), respectively, the numbers of deaths and DALYs clearly declined by -47.8% (-60.7 to -26.4) and -47.7% (-60.7 to -26.2), respectively. In 2019, the middle sociodemographic index (SDI) regions had the highest incidence and prevalence, whereas the low SDI regions had the most mortality and DALYs. Although all of the SDI regions displayed a steady drop in deaths and DALYs between 1990 and 2019, the low-middle and low SDI regions showed increasing trends of incidence and prevalence. Leukemia remained the most common cancer globally in 2019. From 1990 to 2019, the burdens of leukemia, liver cancer, and Hodgkin's lymphoma declined, whereas the incidence and prevalence of other cancers grew, particularly testicular cancer., Conclusions: The global childhood cancer burden in young children has been steadily decreasing over the past three decades. However, the burdens and other characteristics have varied across different regions and types of cancers. This highlights the need to reorient current treatment strategies and establish effective prevention methods to reduce the global burden of childhood cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ren, Liao, Tan, Cheng, Zhu, Zheng, Ma, Mu, Li, Zhang, OuYang, Li, Cui, Ke, Luo, Xiong, Liu, Li, Liang, Zeng, Su and Han.)

Through collecting the relevant moxibustion records of Han medical bamboo slips unearthed in Wuwei and Juyan regions of Gansu province, the situation and characteristics of clinical practice of moxibustion were summarized. In Wuwei Han medical bamboo slips, the contraindications of moxibustion were recorded, with age and time involved. Juyan Han medical bamboo slips mainly recorded the methods of moxibustion at the acupoints located on the back of the body, with clear emphasis and requirement of acupoint selection, single acupoint moxibustion and moxibustion quantity (the numbers of moxa cone) included. These records on bamboo slips initially display the practice and development of moxibustion in Gansu and other northwestern regions of China in the Han Dynasty, providing a certain instruction for the literature research of moxibustion of the excavated Han medical bamboo slips.

Purpose: To evaluate potential regional homogeneity (ReHo) cerebrum function lesions in people with severe obesity and meibomian gland dysfunction (SM) and probe the connection between aberrant cerebrum activity and clinical manifestations., Patients and Methods: An aggregation of 12 patients with SM, and 12 healthy controls (HCs) closely matched in age and gender were enrolled. We applied corneal confocal microscopy and fundus angiography to compare imaging distinctions between the two groups. SMs were required to carefully fill out the Hospital Anxiety Depression Scale (HADS) forms, and a correlation analysis was performed. ReHo was also utilized to appraise partial differences in spontaneous cerebrum function. Receiver operating characteristic (ROC) curves were created to partition ReHo values between patients with SM and the HCs., Results: ReHo values for the left cerebellum (LC), right fusiform gyrus (RFG), left inferior temporal gyrus (LITG), left rectus gyrus (LRG), right thalamus (RT), right caudate (RC), left insula (LI), and left thalamus (LT) of subjects with SM were notably higher than those of the HCs ( P < 0.05). ReHo values of the right middle frontal gyrus (RMFG) in subjects with SM were decreased notably compared to the HCs ( P < 0.05). ReHo values for the RMFG showed a negative correlation with the anxiety scores (ASs; r = -0.961, P < 0.001) and ReHo values for the RFG showed a positive correlation with the depression scores (DSs; r = 0.676, P = 0.016). The areas under the ROC curve were 1.000 ( P < 0.001) for the RMFG, LC, LITG, LRG, RC, LI, and LT and 0.993 ( P < 0.001) for the RFG and RT. The results from the ROC curve analysis indicated that changes in the ReHo values of some brain regions may help diagnose SM., Conclusion: Our research emphasized that patients with SM had lesions in synchronized neural activity in many encephalic areas. Our discoveries may provide beneficial information for exploring the neuromechanics of SM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Tan, Wu, Shen, Zhang, Kang, Ying, Pan, Shu and Shao.)

Objectives: Non-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis., Methods: This prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort., Results: Of the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0-55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02-1.38) and 1.18 (1.01-1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes., Conclusions: NAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Gao, Liao, Cui, Tan, Zeng, Lou, Wang, Xu, Peng, Dai, Zhao, Wang, Ping, Dai, Feng and Han.)

Traditionally, opioid-related disease burden was primarily due to heroin use. However, increases in extra-medical (or non-medicinal use of prescription opioids; NMPOs) use has precipitated the current overdose epidemic in North America. We aim to examine the state-level prevalence of heroin and NMPO dependence and their associations with opioid-related mortality and state-level socio-demographic profiles. Data were pooled from the 2005-2014 National Survey on Drug Use and Health (NSDUH). We examine opioid-related mortality from CDC WONDER (Cause of Death database) by the past year prevalence of DSM-IV heroin and NMPO dependence, by age and sex, and their associations with state-level socio-demographic characteristics from census data. State-level rates of heroin dependence were associated with opioid-related death rates in young and mid-aged adults, while rates of NMPO dependence were associated with opioid-related death rates across all ages. The prevalence of heroin dependence was positively associated with state-level GDP/capita and urbanity. State-level NMPO dependence prevalence was associated with higher unemployment, lower GDP/capita, and a lower high-school completion rate. The prevalence of heroin and NMPO dependence are associated with a broad range of geographical and socio-demographic groups. Taking a wider view of populations affected by the opioid epidemic, inclusive interventions for all are needed to reduce opioid-related disease burden.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition of unknown aetiology associated with a range of disabling symptoms, including post-exertional malaise, chronic fatigue, musculoskeletal pain, orthostatic intolerance, unrefreshing sleep, and cognitive dysfunction. ME/CFS is a heterogeneous disorder, with significant variation in symptom type and severity between individuals, as well as within individuals over time. The diversity of ME/CFS symptom presentation makes management challenging; treatments supported by data from randomised controlled trials may not work for all individuals due to the variability in experienced symptoms. Studies using quantitative N-of-1 observational designs involve repeated outcome measurements in an individual over time and can generate rigorous individual-specific conclusions about symptom patterns and triggers in individuals with ME/CFS. This study aims to explore the feasibility and acceptability of using novel patient-centred N-of-1 observational designs to explore symptom fluctuations and triggers in ME/CFS at the individual level., Methods and Analysis: Individuals with a medical diagnosis of ME/CFS will be recruited through ME/CFS patient organisations to participate in a series of patient-centred N-of-1 observational studies. Using a wrist-worn electronic diary, participants will complete ecological momentary assessments of fatigue, stress, mood, and cognitive demand, three times per day for a period of 6-12 weeks. Personally relevant symptoms and triggers will also be incorporated into the questionnaire design. Physical activity will be objectively measured via an integrated accelerometer. Feasibility and acceptability outcomes will be assessed including the percentage of diary entries completed, as well as recruitment and retention rate, feasibility of analysing and interpreting the data collected, and participant views about participation elicited via a post-study semi-structured interview., Discussion: This study will assess the feasibility and acceptability of patient-centred N-of-1 observational studies to assess diseases with complex presentations such as ME/CFS, as well as provide individual-level evidence about fluctuations and triggers of ME/CFS symptoms that may aid self-management., Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12618001898246. Registered on 22 November 2018., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Critical care admission is a pivotal juncture for older patients undergoing surgery. We aimed to identify the in-hospital and postdischarge outcomes of older postsurgical patients (≥65 years) admitted to the intensive care unit (ICU)., Methods: We collected clinical, morbidity and survival data on all patients aged ≥65 years postsurgically admitted to a tertiary metropolitan ICU between 2014 and 2019., Results: Within this older cohort (n = 370), the oldest patients (≥85 years) had the highest 1-year mortality (RR: 4.00; P < 0.001). Major surgery (RR: 5.67; P < 0.001), emergency surgery (RR: 2.89; P < 0.001) and APACHE III score ≥50 (RR: 2.63; P < 0.001) were associated with reduced 1-year survival., Conclusions: APACHE III score and surgery subtype are strong predictors of post-ICU mortality and may be useful to preoperatively stratify whether surgery and subsequent ICU admission are in patients' best interests. These data may also inform prospective discussions regarding end-of-life care and advanced care planning., (© 2021 AJA Inc’.)

Petroleum-based plastics are associated with environmental pollution problems owing to their non-biodegradable and toxic properties. In this context, renewable and biodegradable bioplastics possess great potential to replace petroleum-based plastics in mitigating these environmental issues. Fabrication of bioplastic films involves a delicate mixture of the film-forming agent, plasticizer and suitable solvent. The role of the plasticizer is to improve film flexibility, whereas the filler serves as a reinforcement medium. In recent years, much research attention has been shifted toward devising diverse methods for enhancing the performance of bioplastics, particularly in the utilization of environmentally benign nanoparticles to displace the conventional hazardous chemicals. Along this line, this paper presents the emergence of nanofillers and plasticizers utilized in bioplastic fabrication with a focus on starch-based bioplastics. This review paper not only highlights the influencing factors that affect the optical, mechanical and barrier properties of bioplastics, but also revolves around the proposed mechanism of starch-based bioplastic formation, which has rarely been reviewed in the current literature. To complete the review, prospects and challenges in bioplastic fabrication are also highlighted in order to align with the concept of the circular bioplastic economy and the United Nations' Sustainable Development Goals.

Bioplastic has been perceived as a promising candidate to replace petroleum-based plastics due to its environment-friendly and biodegradable characteristics. This study presents the chitosan reinforced starch-based bioplastic film prepared by the solution casting and evaporation method. The effects of processing parameters, i.e., starch concentration, glycerol loading, process temperature and chitosan loading on mechanical properties were examined. Optimum tensile strength of 5.19 MPa and elongation at break of 44.6% were obtained under the combined reaction conditions of 5 wt.% starch concentration, 40 wt.% glycerol loading, 20 wt.% chitosan loading and at a process temperature of 70 °C. From the artificial neural network (ANN) modeling, the coefficient of determination (R 2 ) for tensile strength and elongation at break were found to be 0.9955 and 0.9859, respectively, which proved the model had good fit with the experimental data. Interaction and miscibility between starch and chitosan were proven through the peaks shifting to a lower wavenumber in FTIR and a reduction of crystallinity in XRD. TGA results suggested the chitosan-reinforced starch-based bioplastic possessed reasonable thermal stability under 290 °C. Enhancement in water resistance of chitosan-incorporated starch-based bioplastic film was evidenced with a water uptake of 251% as compared to a 302% registered by the pure starch-based bioplastic film. In addition, the fact that the chitosan-reinforced starch-based bioplastic film degraded to 52.1% of its initial weight after 28 days suggests it is a more sustainable alternative than the petroleum-based plastics.

The present study was conducted to optimize the extraction yield of starch from sago ( Metroxylon sagu) pith waste (SPW) with the assistance of ultrasound ensued by the transformation of extracted starch into a higher value-added bioplastic film. Sago starch with extraction yield of 71.4% was successfully obtained using the ultrasound-assisted extraction, with the following conditions: particle size <250 µm, solid loading of 10 wt.%, ultrasonic amplitude of 70% and duty cycle of 83% in 5 min. The rapid ultrasound approach was proven to be more effective than the conventional extraction with 60.9% extraction yield in 30 min. Ultrasound-extracted starch was found to exhibit higher starch purity than the control starch as indicated by the presence of lower protein and ash contents. The starch granules were found to have irregular and disrupted surfaces after ultrasonication. The disrupted starch granules reduced the particle size and increased the swelling power of starch which was beneficial in producing a film-forming solution. The ultrasound-extracted sago starch was subsequently used to prepare a bioplastic film via solution casting method. A brownish bioplastic film with tensile strength of 0.9 ± 0.1 MPa, Young's modulus of 22 ± 0.8 MPa, elongation at break of 13.6 ± 2.0% and water vapour permeability (WVP) of 1.11 ± 0.1 × 10 -8 g m -1 s -1 Pa -1 was obtained, suggesting its feasibility as bioplastic material. These findings provide a means of utilization for SPW which is in line with the contemporary trend towards greener and sustainable products and processes.

Objective: Based on the 2014 version of the International Association of Urological Pathology (ISUP) pathological classification standards, a prediction model that can predict the pathological classification of ISUP ≥2 in patients with prostate cancer (PCa) before radical prostatectomy (RP) was established and evaluated. Methods: The clinical data of 171 patients who had undergone RP from January 2017 to September 2020 in the Second Affiliated Hospital of Soochow University and obtained postoperative pathological results of all specimens were retrospectively collected. The patients were 46-83 (70±7) years old. For patients with RP ISUP pathologic stage as the gold standard, according to the pathological grading is level 2 or higher is divided into two groups(42 patients with ISUP grade=1 and 129 patients with ISUP grade ≥2). the predictors of ISUP pathology grade ≥2 after RP were screened by logistics regression analysis, predictive models were established and ROC curves were used to evaluate the efficacy of each model in diagnosing RP with pathological grade ≥2, and comparisons were conducted by DeLong test. Results: Compared with patients with ISUP grade=1, patients with ISUP grade≥2 had higher prostate specific antigen (PSA) and prostate specific antigen density (PSAD) (14.21(8.57, 24.98)ng/ml vs 7.98(5.41, 12.54)ng/ml, 0.33(0.20, 0.74)μg.L -1 .ml -1 vs 0.16(0.12, 0.24)μg.L -1 .ml -1 ), lower prostate volume (PV) (48.62(34.17,73.99)ml vs 38.94(28.15,54.84)ml)(all P <0.05). Multi-parameter magnetic resonance imaging (mp-MRI) prostate imaging and reporting system (PI-RADS) score, the positive ratio of puncture needles and the pathological grade of puncture ISUP were also significantly different between the two groups (all P <0.05). The combined mp-MRI PI-RADS score ( OR =3.337, 95% CI: 1.990-5.593, P <0.001) and puncture ISUP pathological grading ( OR =4.041, 95% CI: 1.960-8.334, P <0.001) had the highest diagnostic efficacy for pathological grading ≥2 after RP (AUC=0.916, P <0.05). Conclusion: The combined mp-MRI PI-RADS score and puncture ISUP pathological grading had the highest diagnostic efficacy for pathological grading ≥2 after RP.

Purpose: Cancer incidence is rising in low- and middle-income countries, where resource constraints often complicate therapeutic decisions. Here, we perform a cost-effectiveness analysis to identify the optimal adjuvant chemotherapy strategy for patients with stage III colon cancer treated in South African (ZA) public hospitals., Methods: A decision-analytic Markov model was developed to compare lifetime costs and outcomes for patients with stage III colon cancer treated with six adjuvant chemotherapy regimens in ZA public hospitals: fluorouracil, leucovorin, and oxaliplatin for 3 and 6 months; capecitabine and oxaliplatin (CAPOX) for 3 and 6 months; capecitabine for 6 months; and fluorouracil/leucovorin for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Societal costs and utilities were obtained from literature. The primary outcome was the incremental cost-effectiveness ratio in international dollars (I$) per disability-adjusted life-year (DALY) averted, compared with no therapy, at a willingness-to-pay (WTP) threshold of I$13,006.56., Results: CAPOX for 3 months was cost-effective (I$5,381.17 and 5.74 DALYs averted) compared with no adjuvant chemotherapy. Fluorouracil, leucovorin, and oxaliplatin for 6 months was on the efficiency frontier with 5.91 DALYs averted but, with an incremental cost-effectiveness ratio of I$99,021.36/DALY averted, exceeded the WTP threshold., Conclusion: In ZA public hospitals, CAPOX for 3 months is the cost-effective adjuvant treatment for stage III colon cancer. The optimal strategy in other settings may change according to local WTP thresholds. Decision analytic tools can play a vital role in selecting cost-effective cancer therapeutics in resource-constrained settings., Competing Interests: Alexandra M. RogersEmployment: UnitedHealthcare Candice-lee HerbstEmployment: Viatris, Amgen, Sanofi Paul RuffSpeakers' Bureau: Amgen (Inst), Mylan (Inst)Research Funding: MSD (Inst), Janssen Oncology (Inst), Roche (Inst), AstraZeneca (Inst), Novartis (Inst), Pfizer (Inst)Travel, Accommodations, Expenses: Merck Serono, MSD Oncology, Pfizer, Dr Reddy's Laboratories, AstraZeneca, Roche Alfred I. NeugutLeadership: EHE IntlStock and Other Ownership Interests: Stemline TherapeuticsConsulting or Advisory Role: Otsuka, United Biosource Corporation, EHE International, Eisai, GlaxoSmithKlineResearch Funding: Otsuka US (Inst)Expert Testimony: Hospira Chin HurStock and Other Ownership Interests: Cambridge Biomedical and Economic Consulting GroupHonoraria: Kite, a Gilead company, Takeda Science Foundation, Exact SciencesNo other potential conflicts of interest were reported.

Background: Evidence-based management of neuropathic pain is commonly ineffective due to the large variability in response between cases. Patients often have to trial several drugs before finding one that provides adequate relief, leading to increased costs and worsened outcomes. There is thus a need for tools to guide and streamline prescribing decisions in neuropathic pain. N-of-1 trials provide a potentially precise and economical method of selecting between multiple interventions in an individual patient, and merit a feasibility assessment for use in clinical pain practice., Aims: We aim to evaluate the feasibility of N-of-1 trials to compare pregabalin and gabapentin for individual presentations of neuropathic pain., Methods: This is a double-blinded multiple crossover study, with recruitment from existing patients at an outpatient pain clinic in New South Wales, Australia. Participants will undergo three 4-week treatment pairs, comprising 2 weeks of pregabalin (150-600 mg/day) and 2 weeks of gabapentin (900-3600 mg/day), in an individually randomised order. Intervention doses will be derived from participants' existing treatment dose. Medications will be taken orally three times daily. The primary outcome will be pain intensity; measures will be self-reported daily in patient diaries. After completing all three cycles, participants and their physicians will be presented with the results of the trial to form an informed decision about their treatment., Discussion: As a stable yet debilitating condition, neuropathic pain is especially amenable to an N-of-1 study design. A successful trial would represent a significant quality of life improvement for the patient, possibly extending over the course of their lifetime., Competing Interests: Guy Bashford has received research and educational grants from Pfizer. Pfizer had no role in the design of this study, and will have no role in data collection, data analysis, and preparation of any resultant manuscript. Jane Nikles has a commercial interest in N-of-1 Hub Pty Ltd consultancy company. Veronica Murdoch, Samuel Tan, and James McGree, have no interests to declare., (© 2021 Published by Elsevier Inc.)

Importance: With the expansion of multigene testing for cancer susceptibility, Lynch syndrome (LS) has become more readily identified among women. The condition is caused by germline pathogenic variants in DNA mismatch repair genes (ie, MLH1, MSH2, MSH6, and PMS2) and is associated with high but variable risks of endometrial and ovarian cancers based on genotype. However, current guidelines on preventive strategies are not specific to genotypes., Objective: To assess the cost-effectiveness of genotype-specific surveillance and preventive strategies for LS-associated gynecologic cancers, including a novel, risk-reducing surgical approach associated with decreased early surgically induced menopause., Design, Setting, and Participants: This economic evaluation developed a cohort-level Markov simulation model of the natural history of LS-associated gynecologic cancer for each gene, among women from ages 25 to 75 years or until death from a health care perspective. Age was varied at hysterectomy and bilateral salpingo-oophorectomy (hyst-BSO) and at surveillance initiation, and a 2-stage surgical approach (ie, hysterectomy and salpingectomy at age 40 years and delayed oophorectomy at age 50 years [hyst-BS]) was included. Extensive 1-way and probabilistic sensitivity analyses were performed., Interventions: Hyst-BSO at ages 35 years, 40 years, or 50 years with or without annual surveillance beginning at age 30 years or 35 years or hyst-BS at age 40 years with oophorectomy delayed until age 50 years., Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) between management strategies within an efficiency frontier., Results: For women with MLH1 and MSH6 variants, the optimal strategy was the 2-stage approach, with respective ICERs of $33 269 and $20 008 compared with hyst-BSO at age 40 years. Despite being cost-effective, the 2-stage approach was associated with increased cancer incidence and mortality compared with hyst-BSO at age 40 years for individuals with MLH1 variants (incidence: 7.76% vs 3.84%; mortality: 5.74% vs 2.55%) and those with MSH6 variants (incidence: 7.24% vs 4.52%; mortality: 5.22% vs 2.97%). Hyst-BSO at age 40 years was optimal for individuals with MSH2 variants, with an ICER of $5180 compared with hyst-BSO at age 35 years, and was associated with 4.42% cancer incidence and 2.97% cancer mortality. For individuals with PMS2 variants, hyst-BSO at age 50 years was optimal and all other strategies were dominated; hyst-BSO at age 50 years was associated with an estimated cancer incidence of 0.68% and cancer mortality of 0.29%., Conclusions and Relevance: These findings suggest that gene-specific preventive strategies for gynecologic cancers in LS may be warranted and support hyst-BSO at age 40 years for individuals with MSH2 variants. For individuals with MLH1 and MSH6 variants, these findings suggest that a novel 2-stage surgical approach with delayed oophorectomy may be an alternative to hyst-BSO at age 40 years to avoid early menopause, and for individuals with PMS2 variants, the findings suggest that hyst-BSO may be delayed until age 50 years.

Background: Persons with dementia commonly experience a range of behavioural and psychological symptoms, including agitation, aggression, perceptual disturbances, and depression. While psychotropic medications are regularly prescribed to mitigate these symptoms, these agents also carry a broad adverse effect profile. This study aimed to characterize psychotropic medication use in patients with dementia, as well as identify prescribing factors associated with falls in this cohort., Methods: This retrospective study collected longitudinal demographic and medication data from all patients admitted to a neuro-cognitive unit at an Australian metropolitan hospital over a 2-year period. Psychotropic polypharmacy and psychotropic agent use per patient-fortnight were investigated for their association with inpatient falls., Results: All patients (n = 147) were prescribed at least one psychotropic medication, with 96% receiving anti-psychotic medications and 90% receiving benzodiazepines. Patient fall rate was significantly associated with anticholinergic drug use (Incidence rate ratio: 2.2; P  < .001), as well as concomitant use of ≥5 daily psychotropic agents (Incidence rate ratio: 3.1; P  = .001)., Conclusions: Patients with dementia are routinely prescribed a wide variety of psychotropic medications. Use of anticholinergic drugs and psychotropic polypharmacy are correlated with fall incidence in persons with dementia., Competing Interests: The authors confirm that this manuscript is original, and has not previously been published in part or wholly. The authors have no competing interests to declare with regards to this study or manuscript, including any financial interests or support., (© 2021 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Promoting beige adipocyte development within white adipose tissue (WAT) is a potential therapeutic approach to staunch the current obesity epidemic. Previously, we identified homeobox-containing transcription factor HOXC10 as a suppressor of browning in subcutaneous WAT. Here, we provide evidence for the physiological role of HOXC10 in regulating WAT thermogenesis. Analysis of an adipose-specific HOXC10 knockout mouse line with no detectable HOXC10 in mature adipocytes revealed spontaneous subcutaneous WAT browning, increased expression of genes involved in browning, increased basal rectal temperature, enhanced cold tolerance, and improved glucose homeostasis. These phenotypes were further exacerbated by exposure to cold or a β-adrenergic stimulant. Mechanistically, cold and β-adrenergic exposure led to reduced HOXC10 protein level without affecting its mRNA level. Cold exposure induced cAMP-dependent protein kinase-dependent proteasome-mediated degradation of HOXC10 in cultured adipocytes, and shotgun proteomics approach identified KCTD2, 5, and 17 as potential E3 ligases regulating HOXC10 proteasomal degradation. Collectively, these data demonstrate that HOXC10 is a gatekeeper of WAT identity, and targeting HOXC10 could be a plausible therapeutic strategy to unlock WAT thermogenic potentials., (© 2021 by the American Diabetes Association.)

Introduction: Regular endoscopic surveillance is the gold standard Barrett's esophagus (BE) surveillance, yet harms of surveillance for some patients may outweigh the benefits. We sought to characterize physicians' BE surveillance cessation recommendations., Methods: We surveyed gastroenterologists about their BE surveillance recommendations varying patient age, comorbidity, and BE length., Results: Clinicians varied in recommendations for repeat surveillance. Patient age showed the largest variation among decisions, whereas BE length varied the least., Discussion: Age and comorbidities seem to influence BE surveillance cessation decisions, but with variation. Clear cessation guidelines balancing the risks and benefits for BE surveillance are warranted., (Copyright © 2021 by The American College of Gastroenterology.)

C/EBP homologous protein (CHOP), a 29 kDa cellular protein, plays a role in regulating tumor proliferation, differentiation, metabolism, cell death, and in tumor resistance to chemotherapy. Non-small cell lung cancer (NSCLC) is a tumor of the respiratory system and drug resistance is prevalent among NSCLC clinical cell cultures. Herein, our study elucidated the effect of CHOP on NSCLC cells with cisplatin resistance and its mechanism. In a NSCLC cell line with cisplatin-resistance, CHOP expression was decreased, compared with A549 cells. Overexpression of CHOP decreased the cell viability and enhanced cell apoptosis in the cells treated with cisplatin. Expression of CHOP also inhibited the cell proliferation and metastasis. CHOP increased the therapeutic effect of cisplatin on NSCLC cells through the Bcl-2/JNK pathway. In summary, CHOP regulated cisplatin resistance in cells of NSCLC by promoting the expression of apoptotic proteins and inhibiting the Bcl-2/JNK signaling pathway, indicating the antitumor effects of CHOP., Competing Interests: None., (AJTR Copyright © 2021.)