Evaluation of spatial and temporal changes in illicit drug use in the Taipei metropolitan area via wastewater-based epidemiology.

Taiwan, identified as pivotal in the Asian drug trafficking chain, has been experiencing a surge in illicit drug-related issues. Wastewater-based epidemiology (WBE) has emerged as a promising approach for comprehensive evaluation of actual illicit drug usage. This study presents the first WBE investigation of illicit drug consumption in Taiwan based on the analysis of wastewater from four wastewater treatment plants (WWTPs) in the Taipei metropolitan area. Additionally, it demonstrates a high correlation between the amounts of illicit drugs seized and influent concentrations over an extended period of time. The reliability of solid-phase extraction and analysis via high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was validated for 16 illicit drugs (methamphetamine, ketamine, cocaine, codeine, methadone, morphine, meperidine, fentanyl, sufentanil, para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), 3,4-methylenedioxymethamphetamine (MDMA), cathinone, methcathinone, mephedrone (MEPH), and 4-methylethcathinone (4-MEC)). Methamphetamine, ketamine, and 4-MEC were consistently detected in all wastewater samples, underscoring their prevalence in the Taipei metropolitan area. Biochemical oxygen demand (BOD) and ammonia nitrogen (ammonia N) were employed to reduce uncertainty in estimations of population size during back-calculation of illicit drug consumption. The results indicate that methamphetamine was the most consumed drug (175-740 mg day-1 1000 people-1), followed by ketamine (22-280 mg day-1 1000 people-1). In addition, urban-related WWTPs exhibited higher consumption of methamphetamine and ketamine than did the suburban-related WWTP, indicating distinct illicit drug usage patterns between suburban and urban regions. Moreover, an examination of temporal trends in wastewater from the Dihua WWTP revealed a persistent predominance of ketamine and methamphetamine, consistent with statistical data pertaining to seizure quantities and urine test results. The study provides encouraging insight into spatial and temporal variations in illicit drug usage in the Taipei metropolitan area, emphasizing the complementary role of WBE in understanding trends in illicit drug abuse.

Sublobectomy and lymph node sampling are adequate for patients with invasive lung adenocarcinoma presenting as pure ground glass nodules.

PURPOSE: In this study, we aimed to investigate the prognosis of invasive lung adenocarcinoma that manifests as pure ground glass nodules (pGGNs) and confirm the effectiveness of sublobectomy and lymph node sampling in patients with pGGN-featured invasive adenocarcinoma (IAC). MATERIALS AND METHODS: We retrospectively enrolled 139 patients with pGGN-featured IAC, who underwent complete resection in two medical institutions between January 2011 and May 2022. Stratification analysis was conducted to ensure balanced baseline characteristics among the patients. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the groups using Kaplan-Meier survival curves and log-rank test. RESULTS: The 5-year OS and DFS rates for patients with IAC presenting as pGGNs after surgery were 96.5% and 100%, respectively. No lymph node metastasis or recurrence was observed in any of the enrolled patients. There was no statistically significant difference in the 5-year OS between patients who underwent lobectomy or sublobectomy, along with lymph node resection or sampling. CONCLUSION: IAC presented as pGGNs exhibited low-grade malignancy and had a relatively good prognosis. Therefore, these patients may be treated with sublobectomy and lymph node sampling.

Lymphatic endothelial cell-mediated accumulation of CD177+Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma.

Regulatory T (Treg) cells are critical in shaping an immunosuppressive microenvironment to favor tumor progression and resistance to therapies. However, the heterogeneity and function of Treg cells in esophageal squamous cell carcinoma (ESCC) remain underexplored. We identified CD177 as a tumor-infiltrating Treg cell marker in ESCC. Interestingly, expression levels of CD177 and PD-1 were mutually exclusive in tumor Treg cells. CD177+ Treg cells expressed high levels of IL35, in association with CD8+ T cell exhaustion, whereas PD-1+ Treg cells expressed high levels of IL10. Pan-cancer analysis revealed that CD177+ Treg cells display increased clonal expansion compared to PD-1+ and double-negative (DN) Treg cells, and CD177+ and PD-1+ Treg cells develop from the same DN Treg cell origin. Importantly, we found CD177+ Treg cell infiltration to be associated with poor overall survival and poor response to anti-PD-1 immunotherapy plus chemotherapy in ESCC patients. Finally, we found that lymphatic endothelial cells are associated with CD177+ Treg cell accumulation in ESCC tumors, which are also decreased after anti-PD-1 immunotherapy plus chemotherapy. Our work identifies CD177+ Treg cell as a tumor-specific Treg cell subset and highlights their potential value as a prognostic marker of survival and response to immunotherapy and a therapeutic target in ESCC.

Trajectories and risk factors of persistent cough after pulmonary resection: A prospective two-center study.

BACKGROUND: Persistent cough is one of the most frequent complications following lung cancer surgery. To promote optimal recovery, we conducted a study to investigate the trajectories of coughing symptoms and their impact on quality of life (QOL), as well as to identify potential risk factors of persistent cough after pulmonary resection (CAP). METHODS: This prospective observational study assessed patients who underwent pulmonary resection for lung tumor at two medical centers in China. Persistent CAP was evaluated before surgery, at discharge, and 1, 3, and 6 months following surgery using visual analog scale (VAS), cough symptom score (CSS), and Leicester Cough Questionnaire in Mandarin Chinese (LCQ-MC). Univariate and multivariate logistic regression analyses were conducted to explore independent risk factors for persistent CAP. RESULTS: Of the 506 enrolled patients, 130 patients were diagnosed with persistent CAP with an incidence of 25.69%. Compared to the noncough group, patients with persistent CAP reported significantly higher VAS (p < 0.001) and CSS scores (p < 0.001) and experienced worse QOL (p < 0.001) for up to 6 months, particularly at 1 month following surgery. Multivariable regression analysis revealed that a duration of anesthesia exceeding 156 min (odds ratio [OR]: 1.847, 95% confidence interval [CI]: 1.156-2.951, p = 0.010) and gastroesophageal acid reflux (GER) (OR: 3.870, 95% CI: 2.376-6.304, p < 0.001) were independent risk factors of persistent CAP. CONCLUSION: Patients who suffer from persistent CAP face a substantial burden and diminished QOL for an extended period compared to noncough patients. Moreover, prolonged duration of anesthesia and postoperative GER are potential risk factors of persistent CAP.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

BACKGROUND: Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. METHODS: A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. RESULTS: The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). CONCLUSION: A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

Evaluation of Chlamydia trachomatis screening from the perspective of health economics: a systematic review.

Background: Most Chlamydia trachomatis (CT) infections are asymptomatic. The infection can persist and lead to severe sequelae. Therefore, screening for CT can primarily prevent serious sequelae. Aim: To systematically evaluate CT screening from the perspective of health economics, summarize previous findings from different target populations, and make practical recommendations for developing local CT screening strategies. Methods: PubMed, Web of Science, Embase, Cochran Library, and National Health Service Economic Evaluation Database (Ovid) were searched from January 1, 2000, to March 4, 2023. Studies reporting the cost-effectiveness, cost-benefit, or cost-utility of CT screening were eligible to be included. A narrative synthesis was used to analyze and report the results following the PRISMA guidelines. The Consensus on Health Economic Criteria (CHEC) list was used to assess the methodological quality of included studies. Results: Our review finally comprised 39 studies addressing four populations: general sexually active people (n = 25), pregnant women (n = 4), women attending STD and abortion clinics (n = 4), and other high-risk individuals (n = 6). The total number of participants was ~7,991,198. The majority of studies assessed the cost-effectiveness or cost-utility of the screening method. The results showed that the following screening strategies may be cost-effective or cost-saving under certain conditions: performing CT screening in young people aged 15-24 in the general population, military recruits, and high school students; incorporating CT screening into routine antenatal care for pregnant women aged 15-30; opportunistic CT screening for women attending STD and abortion clinics; home-obtained sampling for CT screening using urine specimens or vaginal swab; performing CT screening for 14-30-year-old people who enter correctional institutions (i.e., jail, detention) as soon as possible; providing CT screening for female sex workers (FSWs) based on local incidence and prevalence; adding routine CT screening to HIV treatment using rectal samples from men who have sex with men (MSM). Conclusion: We found that CT screening in general sexually active people aged 15-24, military recruits, high school students, pregnant women aged 15-30, women attending STD and abortion clinics, people entering jail, detention, FSWs, and MSM has health economic value. Due to the different prevalence of CT, diversities of economic conditions, and varying screening costs among different populations and different countries, regions, or settings, no uniform and standard screening strategies are currently available. Therefore, each country should consider its local condition and the results of health economic evaluations of CT screening programs in that country to develop appropriate CT screening strategies.

An Incognito Standardized Patient Approach for Measuring and Reducing Intersectional Healthcare Stigma.

Background: Consistent evidence highlights the role of stigma in impairing healthcare access in people living with HIV (PLWH), men who have sex with men (MSM), and people with both identities. We developed an incognito standardized patient (SP) approach to obtain observations of providers to inform a tailored, relevant, and culturally appropriate stigma reduction training. Our pilot cluster randomized control trial assessed the feasibility, acceptability, and preliminary effects of an intervention to reduce HIV stigma, anti-gay stigma, and intersectional stigma. Methods: Design of the intervention was informed by the results of a baseline round of incognito visits in which SPs presented standardized cases to consenting doctors. The HIV status and sexual orientation of each case was randomly varied, and stigma was quantified as differences in care across scenarios. Care quality was measured in terms of diagnostic testing, diagnostic effort, and patient-centered care. Impact of the training, which consisted of didactic, experiential, and discussion-based modules, was assessed by analyzing results of a follow-up round of SP visits using linear fixed effects regression models. Results: Feasibility and acceptability among the 55 provider participants was high. We had a 87.3% recruitment rate and 74.5% completion rate of planned visits (N=238) with no adverse events. Every participant found the training content "highly useful" or "useful." Preliminary effects suggest that, relative to the referent case (HIV negative straight man), the intervention positively impacted testing for HIV negative MSM (0.05 percentage points [PP], 95% CI,-0.24, 0.33) and diagnostic effort in HIV positive MSM (0.23 standard deviation [SD] improvement, 95% CI, -0.92, 1.37). Patient-centered care only improved for HIV positive straight cases post-training relative to the referent group (SD, 0.57; 95% CI, -0.39, 1.53). All estimates lacked statistical precision, an expected outcome of a pilot RCT. Conclusions: Our pilot RCT demonstrated high feasibility, acceptability, and several areas of impact for an intervention to reduce enacted healthcare stigma in a low-/middle-income country setting. The relatively lower impact of our intervention on care outcomes for PLWH suggests that future trainings should include more clinical content to boost provider confidence in the safe and respectful management of patients with HIV.

Exploring causal mechanisms and essential factors in the prevention and control of chlamydia in Guangdong, Southern China: a study protocol.

BACKGROUND: Chlamydia Trachomatis (CT) is among the most prevalent sexually transmitted diseases (STDs) globally. According to the World Health Organization, more than 131 million people get infected with CT annually. CT is usually transmitted via sexual contact or perinatal exposure and can result in severe long-term complications. In developing nations, particularly, the prevention and control of CT is challenging. Hence, this study will explore the feedback mechanisms of chlamydia prevention and control, as well as identify the essential factors affecting the control and prevention of this infection in China. METHODS: Our study will employ a mixed-methods research design that encompasses both qualitative and quantitative methods. Firstly, we will develop a causal loop diagram (CLD) based on the literature review and optimize it via in-depth interviews with stakeholders. Additionally, we will utilize a quantitative method called MICMAC(Impact Matrix Cross-Reference Multiplication Applied to a Classification tool) to obtain consensus among different stakeholders and pinpoint the key information. Next, the CLD will be transformed into a system dynamics model (SDM) to evaluate the feedback mechanisms within the CLD. The causality in the CLD will be modeled using mathematical equations, which facilitate the transformation into an SDM. As such, we will be able to analyze the dynamic behavior of the system and its response to different decisions. DISCUSSION: Our study offers a systematic perspective on the control and prevention of chlamydia infection through system dynamics modeling, examining the dynamic properties and background factors of the system. The creation of the CLD affords stakeholders the chance to comprehend the functionality of their relationships and improve cooperation. Consequently, by evaluating the outcomes of these simulations, it will be possible to analyze and determine potential interventions and their effects on chlamydia infections. This modeling approach can help us gain insight into the dynamic characteristics of the system, evaluate the potential outcomes of different decisions, and design control strategies to either stabilize the system or adjust its behavior.

HIV/STD prevalence and test uptake among african in Guangzhou, China: an analysis of data from hospital-based surveillance.

Human immunodeficiency virus (HIV) and sexually transmitted diseases (STDs) cause substantial morbidity and mortality both in African and China. However, there is limited data available on the prevalence of HIV/STDs and the uptake of testing experience ever during in China among African migrants. A venue-based survey was conducted at a tertiary hospital in Guangzhou to investigate the prevalence of HIV/STDs through laboratory testing and identify the associated factors. A total of 200 eligible participants completed the survey and bring into the analysis from April to October 2019, and the temporary visitors were excluded. The prevalence rates of HIV, syphilis, NG, CT, and HBsAg among the participants were 1.0%, 2.5%, 1.0%, 1.5%, and 5.5%, respectively. The overall reported rate of HIV/STD testing was 37.0%, with rates of 23.0% for HIV, 16.5% for syphilis, 12.5% for NG, 6.5% for genital herpes, 5.0% for condyloma acuminata, and 2.5% for CT. HIV/STD testing was associated with living environment in Guangzhou, having medical insurance in China, and utilizing health services in China in the past year. HIV/STDs are prevalent among Africans in Guangzhou, and the epidemic is likely to spread due to a significant proportion of unprotected sexual behaviors and low rates of HIV/STD testing. Urgent interventions, including targeted health education, promotion of health service utilization, and active surveillance of HIV/STDs, are needed to reduce the risk of HIV/STD transmission.

Efficacy and safety of immunochemotherapy, immunotherapy, chemotherapy, and targeted therapy as first-line treatment for advanced and metastatic esophageal cancer: a systematic review and network meta-analysis.

Background: The treatment of esophageal cancer has entered a new phase with the development of immunotherapy. The current investigation purpose is to investigate and contrast the efficacy and safety of immunotherapy, immunochemotherapy, chemotherapy, and targeted therapy as first-line treatment for individuals suffering from advanced and metastatic esophageal cancer. Methods: Within the framework of this systematic review and network meta-analysis, clinical trials published or reported in English up until 01 May, 2022, were retrieved from Embase, PubMed, Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov databases, ESMO, and ASCO. The analysis incorporated randomized controlled trials (RCTs) from phase 2 to 3 that evaluated a minimum of two first-line therapeutic regimens for metastatic esophageal cancer were included in the analysis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary clinical outcomes included the incidence of objective response rate (ORR), and adverse events (AEs) of any grade and ≥3 grade. Relative summary data were extracted from included studies by GZ, HS, WS, and TD. For clear statistical analysis, chemotherapy was divided into two categories of fluorouracil-based chemotherapy (FbCT) and fluorouracil-free chemotherapy (FfCT). Bayesian frequentist approach was employed to conduct the network meta-analysis. The indirect intercomparison between regimens was presented with league tables (HRs and 95% CI for OS and PFS, ORs and 95% CI for ORR and AEs). A greater surface value under the cumulative ranking (SUCRA) indicates a higher potential ranking for the corresponding treatment. A further calculation of relative results about esophageal squamous cell cancer was performed in the subgroup analysis. The current protocol for the systematic review has been properly registered on PROSPERO (registration number: CRD42021241145). Findings: The final analysis comprised 17 trials that involved 9128 patients and 19 distinct treatment regimens. Within the scope of investigated immunotherapy (IO) combinations, toripalimab + FfCT (tori + FfCT) demonstrated the best OS advantages (tori + FfCT vs. FbCT, HR 0.57, 95% CI 0.38-0.85; tori + FfCT vs. FfCT, HR 0.58, 95% CI 0.43-0.78). In terms of PFS, camrelizumab + FfCT (cam + FfCT) demonstrated the best PFS advantages (FbCT vs. cam + FfCT, HR 1.79, 95% CI 1.22-2.63; FfCT vs. cam + FfCT, HR 1.79, 95% CI 1.47-2.17). Nivolumab + FbCT (nivo + FbCT vs. FfCT, OR 3.29, 95% CI 1.43-7.56) showed the best objective responses. Compared to the conventional chemotherapy regimen, the toxicity was observed to be the slightest for the tori + FfCT (FbCT vs. tori + FfCT, OR 3.07, 95% CI 1.22-7.7) and sintilimab + FfCT (FbCT vs. sin + FfCT, OR 2.93, 95% CI 1.16-7.37). The results in this study were evaluated as having a low heterogeneity since the I2 value was ≤25% in all analyses. Interpretation: Compared to foreign IO combinations, sin + FfCT, tori + FfCT, cam + FfCT, and tisle + FbCT are superior first-line treatment options for patients with advanced and metastatic esophageal cancer. Although foreign IO combinations, such as pembro + FbCT and nivo + FbCT obtained better objective response rates than other IO combinations, the addition of chemotherapy to IO worsens the safety profiles. Our findings could provide complementary evidence for current guideline recommendations. Funding: This work was supported by a grant from the Science and Technology Program of Guangzhou, China (202206010103); and Natural Science Foundation of Guangdong Province (2022A1515012469).

Effectiveness of chlamydia Test and Treat strategy in preventing adverse pregnancy outcomes: protocol for a randomized controlled trial.

Introduction: Chlamydia trachomatis is one of the most common bacterial sexually transmitted infections worldwide, and is associated with an increased risk of adverse pregnancy outcomes. However, whether providing chlamydia screening and treatment during the first trimester of pregnancy could reduce adverse pregnancy outcomes is still not clear. This study reports a randomized controlled trial (RCT) protocol to evaluate the effectiveness of chlamydia Test and Treat during early pregnancy in preventing adverse pregnancy outcomes in China. Methods and analysis: This trial is a multi-center two-arm RCT targeting 7,500 pregnant women in early pregnancy (6-20 weeks). The inclusion criteria included: 18-39 years old, on their first antenatal visit, in the first trimester, and plan to deliver in the study cities. Following a block randomization procedure, every block of twenty women will be randomly assigned in a 1:1 ratio into two arms: (1) a Test and Treat arm in which women receive free chlamydia testing immediately after enrollment and people tested as chlamydia positive will receive standardized treatment and partner treatment; (2) a control arm in which women receive regular prenatal care without receiving testing during the pregnancy period, but collect urine samples and test them after delivery or indicating a chlamydia-related complication during pregnancy happens. The primary outcome is a composite of eight adverse events rate at delivery between two arms, including stillbirth, infant death, spontaneous abortion, preterm labor, low birth weight, premature rupture of membranes, postpartum endometritis, and ectopic pregnancy. Secondary outcomes include the cost-effectiveness of the intervention, the proportion of people tested with chlamydia infection, the proportion of tested-positive patients that received treatment, and the proportion of people who were cured 1 month after the treatment initiation. Urine specimens will be collected and tested for chlamydia by using Nucleic Acid Amplification Test. Data will be analyzed according to the intention-to-treat principle. Discussion: This trial will test the hypothesis that early testing and treating of chlamydia can reduce the risk for adverse pregnancy outcomes and may help in developing chlamydia screening guidelines in China and other countries with a similar prevalence of chlamydia infection. Trial registration: Chinese Clinical Trials Registry, ChiCTR2000031549. Registered on April 4, 2020.

Early and Persistent Dysphagia Relief Predicts Tumor Response in Esophageal Squamous Cell Carcinoma Patients Treated with Immunochemotherapy.

BACKGROUND: In this prospective study, we aimed to investigate the role of patient-reported dysphagia relief in predicting pathological tumor responses to neoadjuvant immunochemotherapy (NAIC) in locally advanced esophageal squamous cell carcinoma (ESCC) patients. METHODS: This study was designed as a multi-center, prospective study including ESCC patients who received NAIC in the discovery and validation cohorts. The patients' responses to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-OES 18 and QLQ-C30 were collected at multiple time points. Subsequent time point-intensive esophageal cancer-specific dysphagia trajectories were depicted using growth mixture modeling (GMM) analysis. Furthermore, univariate and multivariate binary logistic regression was used to assess the independent predictors for pathological tumor responses. RESULTS: A total of 120 patients from the discovery cohort and 42 patients from the validation cohort were included in the analysis. In the discovery cohort, 19 (22.9%) of the 83 patients achieved pCR status. In the independent validation cohort, 24 patients underwent surgery, and 9 (37.5%) patients achieved pCR status. Trajectory analysis showed that, in the pCR group, the beginning of rapid declines in the slope occurred on days 3, 6, and 9. Further multivariate analysis showed that the degree of dysphagia relief (△dysphagia%) was the only significant independent predictor for pCR status (OR = 3.267, 95% CI 1.66-6.428, P < 0.001). The AUC value for △dysphagia% was 0.961 (95% CI: 0.922-0.999, P < 0.001). CONCLUSION: The current study demonstrated that a longitudinal patient-reported outcome (PRO) was an easily obtained, cost-effective, and noninvasive tool for predicting tumor responses to neoadjuvant immunochemotherapy.

m6A-binding protein IGF2BP1 promotes the malignant phenotypes of lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD), the most common type of lung cancer, poses a significant threat to the life of patients. N6-methyladenosine modification is the most abundant epigenetic modification and may play an important role in the lung carcinogenesis. IGF2BP1 is a newly discovered m6A-binding protein, but little is known about its role in LUAD. Methods: Data from TCGA, GEO, Kaplan-Meier Plotter, and GEPIA databases were systematically analyzed to access the expression and prognostic value of IGF2BP1 on LUAD. Real-time polymerase chain reaction, Western blot, and immunohistochemistry were performed to detect the mRNA and protein level of IGF2BP1 in LUAD tissues and para-carcinoma tissues. Functional cell experiments, including Cell Counting Kit-8 assay, Transwell invasion assay, wound healing assay, Annexin V-FITC/PI double-staining assay, and TUNEL assay, were used to investigate the functions of IGF2BP1 on LUAD cell proliferation, invasion, migration, and apoptosis, respectively. The top 50 genes that were positively or negatively related to the expression of IGF2BP1 were identified, and pathway enrichment analysis was performed. m6A modification sites within IGF2BP1-related genes were predicted by SRAMP. Result: 16 m6A regulators were significantly differentially expressed in LUAD tissues. IGF2BP1 was upregulated in LUAD tissues compared with para-carcinoma tissues. High expression of IGF2PB1 was significantly associated with higher clinical stages and poor prognosis of LUAD patients. Furthermore, our functional experiments indicated that IGF2BP1 facilitated cell proliferation, invasion, and migration and suppressed apoptosis in LUAD. Functional enrichment analysis of IGF2BP1-related genes indicated enrichment in several pathways related to oncogenesis. Additionally, m6A modification sites were detected within IGF2BP1-related genes. Conclusions: Our findings demonstrate that IGF2BP1 plays a contributory role in the development and progression of LUAD. IGF2BP1 has the potential to become a prognostic predictor and therapeutic target for LUAD.

Dynamic alteration in SULmax predicts early pathological tumor response and short-term prognosis in non-small cell lung cancer treated with neoadjuvant immunochemotherapy.

Introduction: Biomarkers predicting tumor response to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) are still lacking despite great efforts. We aimed to assess the effectiveness of the immune PET Response Criteria in Solid Tumors via SULmax (iPERCIST-max) in predicting tumor response to neoadjuvant immunochemotherapy and short-term survival in locally advanced NSCLC. Methods: In this prospective cohort study, we calculated SULmax, SULpeak, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their dynamic percentage changes in a training cohort. We then investigated the correlation between alterations in these parameters and pathological tumor responses. Subsequently, iPERCIST-max defined by the proportional changes in the SULmax response (△SULmax%) was constructed and internally validated using a time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC) value. A prospective cohort from the Sun Yat-Sen University Cancer Center (SYSUCC) was also included for external validation. The relationship between the iPERCIST-max responsiveness and event-free survival in the training cohort was also investigated. Results: Fifty-five patients with NSCLC were included in this study from May 2019 to December 2021. Significant alterations in post-treatment SULmax (p < 0.001), SULpeak (p < 0.001), SULmean (p < 0.001), MTV (p < 0.001), TLG (p < 0.001), and tumor size (p < 0.001) were observed compared to baseline values. Significant differences in SULpeak, SULmax, and SULmean between major pathological response (mPR) and non-mPR statuses were observed. The optimal cutoff values of the SULmax response rate were -70.0% and -88.0% using the X-tile software. The univariate and multivariate binary logistic regression showed that iPERCIST-max is the only significant key predictor for mPR status [OR = 84.0, 95% confidence interval (CI): 7.84-900.12, p < 0.001]. The AUC value for iPERCIST-max was 0.896 (95% CI: 0.776-1.000, p < 0.001). Further, external validation showed that the AUC value for iPERCIST-max in the SYSUCC cohort was 0.889 (95% CI: 0.698-1.000, p = 0.05). Significantly better event-free survival (EFS) in iPERCIST-max responsive disease (31.5 months, 95% CI 27.9-35.1) than that in iPERCIST-max unresponsive disease (22.2 months, 95% CI: 17.3-27.1 months, p = 0.024) was observed. Conclusion: iPERCIST-max could better predict both early pathological tumor response and short-term prognosis of NSCLC treated with neoadjuvant immunochemotherapy than commonly used criteria. Furthermore, large-scale prospective studies are required to confirm the generalizability of our findings.