Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.

BACKGROUND: Despite advances in therapeutic strategies, resistance to immunotherapy and the off-target effects of targeted therapy have significantly weakened the benefits for patients with melanoma. MAIN BODY: Alternative splicing plays a crucial role in transcriptional reprogramming during melanoma development. In particular, aberrant alternative splicing is involved in the efficacy of immunotherapy, targeted therapy, and melanoma metastasis. Abnormal expression of splicing factors and variants may serve as biomarkers or therapeutic targets for the diagnosis and prognosis of melanoma. Therefore, comprehensively integrating their roles and related mechanisms is essential. This review provides the first detailed summary of the splicing process in melanoma and the changes occurring in this pathway. CONCLUSION: The focus of this review is to provide strategies for developing novel diagnostic biomarkers and summarize their potential to alter resistance to targeted therapies and immunotherapy.

Identification of RESP18 Gene Mutations Linked to Hereditary Non-Syndromic Cleft Lip and Palate in a Southern Chinese Family.

BACKGROUND Non-syndromic cleft lip with cleft palate (NSCLP) is one of the most common congenital birth defects worldwide; it causes lifelong problems and imposes burdens on patients and their families. This study aimed to describe the genomic analysis and identification of de novo regulated endocrine-specific protein 18 (RESP18) rs2385404 and rs2385405 gene polymorphisms associated with NSCLP in a southern Chinese family and to improve prevention, treatment, and prognosis of NSCLP. MATERIAL AND METHODS We performed a genome-wide association study (GWAS) to investigate the association of NSCLP phenotype with gene mutation. We investigated a 5-persons NSCLP family to screen the genetic variation of Han nationality in southern Chinese. Whole-genome sequencing (WGS) was used to detect all candidate genetic variants, and whole-exome sequencing (WES) was implemented to further verify mutations. The Clinical Variation Data Base (ClinVar) was employed for screening gene mutations. Finally, Sanger sequencing was applied to verify gene variations. RESULTS The combined analysis of WGS, WES, and ClinVar showed that a total of 9 variation positions overlapped among the 3 study cohorts. Sanger sequencing verified Glu amino acid variation in 2 mutation sites (rs2385404, rs2385405) from the RESP18 gene, which caused abnormal RESP18 function and was associated with hereditary NSCLP. CONCLUSIONS The combined genomic results showed that 2 mutations (rs2385404 and rs2385405) of the RESP18 gene were related to NSCLP in the family. The RESP18 gene may play an important role in the etiology and pathogenesis of cleft lip and palate.

The relationship between longer leukocyte telomeres and dNCR in non-cardiac surgery patients: a retrospective analysis.

BACKGROUND: Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. METHODS: For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. RESULTS: Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7-26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01-54.84; P < 0.001], following adjustment of age (OR, 12.33; 95% CI, 3.29-46.24; P < 0.001). The dNCR incidence based on LTL values of these patients, the area under the receiver operating characteristic (ROC) curve was 0.79 (95% CI, 0.722-0.859; P < 0.001). At an optimal cut-off value of 0.959, LTL values offered respective specificity and sensitivity values of 64.7% and 87.5%. CONCLUSIONS: In summary, the current study revealed that the incidence of dNCR was strongly associated with prolonged LTL. Furthermore, this biomarker could help identify high-risk patients and offer insight into the pathophysiology of dNCR.

Determination of rebamipide in human plasma by a validated liquid chromatography-tandem mass spectrometry: Application in pharmacokinetics research.

A new method for the determination of rebamipide in human heparin sodium plasma by LC-MS was established and its methodology was validated. In this method, protein precipitation method was used to pretreat the samples and the rebamipide-d4 isotope of rebamipide was used as the internal standard. In the multi reaction monitoring mode, the electrospray ion source was used as the ionization technolog and LC-MS was used for detection and analysis. The liquid chromatographic conditions were: 00B-4605-AN (Kinetex® XB-C18 100A 50mm × 2.1mm, 5µm); mobile phase A: 0.1% FA and 1 mM NH4FA aqueous solution, mobile phase B: 0.1% FA and 1mM NH4FA 90% ACN solution, flow rate: 0.300mL/min, injection volume: 10uL, column temperature: 30oC, collection time: 3 min, injector temperature control: 5oC. The retention time of rebamipide and rebamipide-d4 were 1.32min and 1.31min, respectively. The lower limit of quantification was 1ng/mL and the calibration map of rebamipide in the concentration range of 1 to 800ng/mL was linear (R2 >0.990, n=11). The CV% values of the inter and intra batch precision of the method were both less than 15.0%. This method has been successfully applied to pharmacokinetic studies to evaluate the main pharmacokinetic parameters of rebamipide.

The characteristics of registered acupuncture clinical trials enrolling cancer patients.

PURPOSE: This study sought to explore and summarize the global state of acupuncture clinical trials enrolling cancer patients included in international registries to date. METHODS: All relevant trials evaluating acupuncture-related interventions for the treatment of cancer that were registered in 16 trial registries from January 1, 2001, through December 31, 2020, were identified. Subsequent publications related to these trials were additionally retrieved from the PubMed, Cochrane Library, Embase, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and Wanfang databases. We compared information included in these registries regarding completed trials with any associated publications, with a focus on study design, sample size, and selective reporting, based on the registered protocol. RESULTS: In total, 222 eligible trials across 19 countries were identified. These trials included 17 specific cancer types and 32 symptoms. The five most common cancer types were breast cancer, head and neck cancer, colorectal cancer, lung cancer, and gastric cancer, accounting for almost half of all registered trials (48.2%). The top five symptoms included in these trials were chemotherapy-induced peripheral neuropathy (CIPN), cancer-related pain, cancer-related fatigue, chemotherapy-induced nausea and vomiting (CINV), and gastrointestinal dysfunction. The overall rate of article publication was low, with publications being associated with just 33.3% of these registered trials. CONCLUSIONS: This review is the first snapshot of the landscape of acupuncture clinical trials registered in international trial registries, providing a methodological basis for the management of common treatment- and disease-related side effects among cancer patients undergoing acupuncture and offering useful information that will guide future acupuncture-focused research.

Multi-focused psychosocial residential rehabilitation interventions improve quality of life among cancer survivors: a community-based controlled trial.

BACKGROUND: Even though multi-focused psychosocial residence rehabilitation intervention (MPRRI) programs are widely implemented by the Shanghai Cancer Rehabilitation Club, these programs have not been rigorously evaluated. In this study, we evaluated the effects of a 21-day MPRRI program, on the quality of life (QoL) among cancer survivors. METHODS: A total of 388 cancer patients were enrolled to either receive the 21-day MPRRI (n = 129) intervention or a waiting-list comparison (WLC) intervention (n = 259). The intervention group was offered community-based 21-day MPRRI program, combining supportive-expressive group, cognitive-behavioral therapy, and Guolin Qigong. QoL was measured using the European Organization for Research and Treatment Quality of Life Version 3 Questionnaire. Multivariable linear models were used to compare changes in QoL values between the two groups. RESULTS: After adjustment for the QoL score and other covariates at baseline, there was no significant difference in global health status (mean = 3.8, 95% CI - 1.3-9.0, P = 0.14) between the two groups after 6 months intervention. While compared with the WLC group, the intervention group showed significant improvements in the QoL score (all P < 0.05); however, there were no clinically relevant changes in subscales including emotional functioning (ES = 0.58), cognitive functioning (ES = 0.53), pain (ES = 0.52), physical functioning (ES = 0.36), and insomnia (ES = 0.30). CONCLUSIONS: These preliminary results suggest the MPRRI program is both feasible and acceptable intervention for cancer survivors in community settings and is effective in significant improving QoL above.

Physical exercise, vegetable and fruit intake and health-related quality of life in Chinese breast cancer survivors: a cross-sectional study.

INTRODUCTION: Breast cancer has long-term effects on health-related quality of life (HRQOL) of cancer survivors after treatment. Few research studies have focused on the association between health behaviors and HRQOL of Chinese breast cancer survivors (BCS). The aim of this study was to examine the separate and combined influence of physical exercise, vegetable and fruit intake on health-related quality of life of BCS. METHODS: A cross-sectional study was conducted among BCS from April to July 2013, in Shanghai, China. Data were collected using a self-reported questionnaire, which included questions about basic socio-demographic characteristics, health conditions and treatments, health behaviors and HRQOL. HRQOL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) simplified Chinese V3.0 version and the Functional Assessment of Cancer Therapy-General (FACT-G) simplified Chinese 4th version. Multiple linear regression models were performed to estimate the effects of physical exercise, vegetable and fruit intake as well as the effects of health behavior patterns on HRQOL adjusting for potential confounding variables. RESULTS: Exercisers reported significantly higher scores in most HRQOL dimensions than non-exercisers. Participants who ate more than 250 g of vegetables reported significantly higher scores in most HRQOL dimensions than participants who ate equal or less than 250 g of vegetables. Participants who ate fruit every day reported significantly higher scores in all HRQOL dimensions than those who did not eat fruit every day (P Adjusted ≤ 0.032), except symptom subscales. All subscale scores and total scores of HRQOL, except symptom subscales, were positively associated with the number of adopted healthy lifestyle behaviors (P Trend ≤ 0.003). Compared to participants who adopted only one healthy behavior, participants who adopted two or three healthy behaviors both reported significantly higher HRQOL scores. CONCLUSION: Physical exercise, enough vegetable and fruit intake are positively associated with HRQOL of BCS. BCS who adopted several healthy behaviors simultaneously had better HRQOL than one healthy behavior alone. Healthy behaviors, including engagement in exercise, proper diet, especially comprehensive lifestyle behavior interventions, should be valued in improving HRQOL of BCS.

The influence of comorbid chronic diseases and physical activity on quality of life in lung cancer survivors.

PURPOSE: This study aimed to evaluate the influence of comorbid chronic diseases (CCD) and physical activity (PA) on quality of life (QOL) in lung cancer survivors (LCSs). METHODS: The study used a cross-sectional study design. A total of 701 LCSs were recruited from 17 comprehensive cancer rehabilitation clubs in Shanghai, China. Measurements used included the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy -General version 4 questionnaire (FACT-G). Independent variables were CCD and PA. Multiple linear regression models were used to control for the effect of sociodemographic characteristic. RESULTS: Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 and FACT-G scales when compared to subjects without CCD, indicating poorer QOL. Subjects with PA generally reported higher scores for most EORTC QLQ-C30 and FACT-G scales when compared to subjects without PA, indicating better QOL. The influences of five times and more PA per week were larger than the influence of less than five times PA per week. Subjects without CCD and with PA generally reported similar scores for most EORTC QLQ-C30 and FACT-G scales when compared to others without CCD and PA. Subjects with CCD and PA generally reported higher scores for most EORTC QLQ-C30 and FACT-G scales when compared to other LCSs with CCD and without PA. CONCLUSIONS: CCD have significantly negative influence on QOL. PA has significantly positive influence on QOL among the LCSs with CCD, not among the other LCSs without CCD.

Comorbid chronic diseases and their associations with quality of life among gynecological cancer survivors.

BACKGROUND: Many gynecological cancer survivors (GCS) have comorbid chronic diseases (CCD). This study was to estimate the impacts of CCD on quality of life (QOL) in GCS. METHODS: We collected cross-sectional self-reported survey data from 598 GCS between April and July 2013, in Shanghai, China. All the subjects were asked to complete a questionnaire containing the European Organization for Research and Treatment quality of life version 3 questionnaire (EORTC QLQ-C30) and questions on socio-demographic characteristics and CCD. In order to mitigate the bias caused by confounding factors, multiple linear models were employed to calculate adjusted means of QOL scores. RESULTS: Approximately three-quarters of subjects reported at least one CCD. The highest overall prevalence of all CCD was found in endometrial cancer survivors. Subjects with CCD generally reported lower scores for most EORTC QLQ-C30 scales when compared to subjects without CCD, indicating poorer QOL, particularly for cardiovascular diseases, respiratory diseases, digestive diseases, and musculoskeletal disease. CONCLUSIONS: The CCD are common health problems among GCS. CCD have significantly negative influence on QOL, and GCS with CCD generally reported lower QOL scores. These findings suggested comprehensive cares for GCS.

Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages.

Histone deacetylases (HDACs) regulate inflammatory gene expression, as indicated by the potent antiinflammatory activity of pan-HDAC inhibitors. However, the specific contribution of each of the 11 HDAC proteins to the inflammatory gene expression program is unknown. Using an integrated genomic approach, we found that Hdac3-deficient macrophages were unable to activate almost half of the inflammatory gene expression program when stimulated with LPS. A large part of the activation defect was attributable to loss of basal and LPS-inducible expression of IFN-ß, which maintains Stat1 protein levels in unstimulated cells and acts in an autocrine/paracrine manner after stimulation to promote a secondary wave of Stat1-dependent gene expression. Loss of Hdac3-mediated repression of nuclear receptors led to hyperacetylation of thousands of genomic sites and associated gene derepression. The up-regulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), a nuclear receptor target, had a causative role in the phenotype because its chemical inhibition reverted, albeit partially, the Ifn-ß activation defect. These data indicate a central role for Hdac3 in inflammation and may have relevance for the use of selective Hdac inhibitors as antiinflammatory agents.

[Advances in psychosocial interventions on quality of life of cancer survivors].

In recent years, there has been increasing recognition of the importance of psychosocial interventions' studies on quality of life in cancer survivors because of improving cancer survival rate. This paper was an integrative literatures review of various psychosocial interventions including cognitive behavioral therapy, group-based supportive therapy, counseling or psychotherapy, education or psychoeducation and music therapy et al, and analyzing the complexity of psychosocial interventions' RCTs in oncology and the current characteristic of these studies in China.

Association between MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population: a systematic review and meta-analysis.

The association between the C3435T polymorphism in the MDR1 gene and refractory epilepsy remains controversial. The association appears to be influenced by ethnicity and region. We have performed a systematic review and meta-analysis to assess the link between the MDR1 C3435T polymorphism and refractory epilepsy in the Chinese population. We searched the Cochrane Library, MIDLINE, EMBASE, CBM disc, CNKI, VIP, and WANFANG databases for literature published through August 2013 for case-control studies that evaluated the association between the MDR1 C3435T polymorphism and refractory epilepsy. Twenty-one case-control studies involving 4269 patients (1863 cases in the group with drug-resistant epilepsy and 2406 in the group with drug-responsive epilepsy) were included in the systematic review and meta-analysis. The analysis showed that there were significantly more cases with the MDR1 3435 CC genotype in the group with drug-resistant epilepsy than in the group with drug-responsive epilepsy [odds ratio (OR)=1.50, 95% confidence interval (CI)=1.09-2.06, P=0.01]. In a subanalysis of patients from the southern regions of China, the correlation was not significant [odds ratio (OR)=1.2, 95% confidence interval (CI)=0.89-1.64, P=0.24]. The relationship established in a subset of the Chinese population between the MDR1 C3435T polymorphism and refractory epilepsy will guide epilepsy treatment and development of new AEDs.

[Associations between physical exercise and quality of life in breast cancer patients].

OBJECTIVE: To investigate the associations between physical exercise and quality of life in breast cancer patients. METHODS: A cross-sectional study was conducted among 3 344 community breast cancer patients between April and July 2013 in Shanghai, China. Data were collected using a questionnaire, including socio-demographic situation, cancer survival and health behaviors, and scores of EORTC QLQ-C30 Simplified Chinese version and FACT-G Simplified Chinese version. RESULTS: Among a total of 3 344 breast cancer patients, the patients doing exercise reported significantly higher EORTC physical functioning scores, role functioning scores, emotional functioning scores, global health scores, and FACT-G physical well-being scores, social well-being scores, emotional well-being scores, functional well-being scores, and FACT-G total scores than the patients who didn't take exercise (P < 0.05, P(Adjusted)<0.05) . Breast cancer patients who did exercise more than or equal to 5 times/week reported significantly higher EORTC role functioning scores, cognitive functioning scores, emotional functioning scores, global health scores and FACT-G physical well-being scores, functional well-being scores, and FACT-G total scores than patients who did exercise less than 5 times/week (P < 0.05, P(Adjusted)<0.05 ). CONCLUSIONS: There are active associations between physical exercise and quality of life in breast cancer patients. Engagement in physical exercise is beneficial to breast cancer patients with long-term survival.

[Associations between vegetables and fruit intake and quality of life in breast cancer patients].

OBJECTIVE: To investigate the associations between vegetables and fruit intake and quality of life in breast cancer patients. METHODS: A total of 3 344 community breast cancer patients were selected through cluster sampling method between April and July 2013, in Shanghai, China. Data were collected using a questionnaire, which included socio-demographic situation, cancer survival and health behaviors(i.e. vegetables or fruit intake, exercise), European Organization for Research and Treatment (EORTC) QLQ-C30 Simplified Chinese version(3rd edition) and Functional Assessment of Cancer Therapy scale (FACT-G) Simplified Chinese version(4th edition) were used to evaluate the quality of life. Crude quality of life scores were compared between groups. Multiple linear models were used to calculate and compare adjusted means of quality of life between groups, controlling relevant factors. RESULTS: After adjusting relevant factors, breast cancer patients who ate more than 250 g vegetables reported higher EORTC physical functioning scores, cognitive functioning scores, emotional functioning scores, global health scores than patients who ate equal or less than 250 g vegetables(respectively (80.79 ± 0.85) vs (79.34 ± 0.82), (80.07 ± 1.03) vs (77.84 ± 0.99), (84.17 ± 0.95) vs (82.76 ± 0.92), (65.75 ± 1.50) vs (62.92 ± 1.45)), t values respectively were 2.76, 3.54, 2.40, 3.17, all P values were <0.05; and breast cancer patients who ate more than 250 g vegetables reported higher FACT-G social well-being scores, function well-being scores, FACT-G total scores than patients who ate equal or less than 250 g vegetables (respectively (17.92 ± 0.40) vs (17.31 ± 0.39), (14.86 ± 0.42) vs (14.34 ± 0.40), (74.78 ± 1.01) vs (73.05 ± 0.97)), t values respectively were 2.49, 2.05, 2.90, all P values were <0.05. After adjusting relevant factors, breast cancer patients who ate fruit everyday reported higher EORTC physical functioning scores, role functioning scores, cognitive functioning scores, emotional functioning scores, social functioning scores, global health scores than patients who didn't eat fruit everyday (respectively (80.40 ± 0.82) vs (79.22 ± 0.87), (89.81 ± 1.00) vs (88.06 ± 1.05), (79.78 ± 0.99) vs (77.11 ± 1.04), (84.43 ± 0.92) vs (81.56 ± 0.97), (77.95 ± 1.25) vs (75.56 ± 1.31), (65.48 ± 1.44) vs (61.74 ± 1.51)), t values respectively were 2.15, 2.64, 4.07, 4.71, 2.89, 4.02, all P values were <0.05; and breast cancer patients who ate fruit everyday reported higher FACT-G physical well-being scores, social well-being scores, emotional well-being scores, functional well-being scores, FACT-G total scores than patients who didn't eat fruit everyday(respectively (23.35 ± 0.26) vs (22.85 ± 0.28), (17.91 ± 0.39) vs (16.98 ± 0.41), (18.59 ± 0.22) vs (18.18 ± 0.23), (14.79 ± 0.40) vs (14.17 ± 0.42), (74.71 ± 0.97) vs (72.17 ± 1.02)), t values respectively were 2.92, 3.65, 2.91, 2.35, 4.05 , all P values were <0.05. CONCLUSION: There are active associations between vegetables / fruit intake and quality of life in breast cancer patients. Proper diet may help improve quality of life in breast cancer patients.

The influence of novel coronavirus pneumonia on chronic disease management of asthma-a narrative review.

Background and Objective: The coronavirus disease 2019 (COVID-19) pandemic has taken a huge global toll on all fronts, creating new challenges for the diagnosis and treatment of respiratory diseases. For chronic management of asthma, on the one hand, the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the asthma disease itself; on the other hand, in order to control the spread of the pandemic, forced isolation, mask-wearing and various disinfection measures also have an impact on the condition and medication of asthma patients. This article reviews the changes in chronic asthma management under the COVID-19 pandemic to provide reference for chronic disease management of asthma after the pandemic and for various public health emergencies in the future. Methods: Online searching of literature was performed. The National Center for Biotechnology Information (NCBI), PubMed, Google Scholar, and EMBASE were searched. Key Content and Findings: COVID-19 has had a huge impact on the world, and has also brought new challenges to the diagnosis and treatment of asthma and chronic disease management. On the one hand, the existence of the 2019 novel coronavirus directly affects the asthma disease itself, on the other hand, due to the particularity of the asthma disease itself, different levels of isolation and controls can cause patients with different degrees of medical difficulties; in addition, the application of various disinfectants in the environment also increases the risk of acute attacks of asthma patients, as well as mask-wearing, vaccination, anxiety about the disease, panic, etc., all of which have posed various degrees of impact on the condition and psychology of asthma patients. Conclusions: The pandemic of COVID-19 has brought many difficulties to the chronic disease management of asthma, and has had a certain impact on the disease control of asthma patients. In the era with overflowing information, internet hospital is the current trend, and there is a long way to go for effectively penetrating medical resources virtually via the internet into chronic disease management of asthma.

FTO in Lung Cancer: Its Progression and Therapeutic Potential.

One of the most fatal and frequent malignancies on the planet is lung cancer. Its occurrence and development are the results of multifactorial and multigenic interactions. In recent years, RNA N6-methyladenosine transferase (FTO) has gained significant attention in the field of oncology. FTO is the first RNA demethylase to be found to control target mRNA demethylation. The growth, proliferation, and metastasis of tumor cells are greatly influenced by FTO. Recent studies have found that imbalanced m6A methylation regulatory proteins can induce disruption of downstream RNA metabolism, strongly affecting tumor development. This paper provides an overview of the relationship between FTO and lung cancer, discussing the mechanisms by which FTO is involved in lung cancer and its potential clinical applications.

A rare adverse effect in inebilizumab therapy for neuromyelitis optica spectrum disorder: a case report.

Inebilizumab is one of the monoclonal antibodies approved as maintenance therapy for aquaporin-4 immunoglobulin G-seropositive neuromyelitis optica spectrum disorder (NMOSD). It is a humanized monoclonal antibody targeting cluster of differentiation 19 (CD19). Common adverse reactions include urinary tract infections, nasopharyngitis, arthralgia, infusion reactions, headaches and a decrease in immunoglobulin levels. Here, we present a case of an NMOSD patient who experienced transient hyperCKaemia after the use of inebilizumab. The adverse reactions of this very rare monoclonal antibody drug improved after discontinuation.

TGFß2 Promotes the Construction of Fibrotic and Immunosuppressive Tumor Microenvironment in Pancreatic Adenocarcinoma: A Comprehensive Analysis.

Pancreatic adenocarcinoma (PAAD) was characterized by dense fibrotic stroma and immunosuppressive tumor microenvironment (TME). TGFß signaling pathways are highly activated in human cancers. However, the role of TGFß2 in TME of PAAD remains to be elucidated. In this study, we showed that TGFß2 was expressed at a relatively high level in PAAD tissues or cancer cells. Moreover, its high expression predicted unfavorable prognosis. In PAAD, gene set enrichment analysis showed that TGFß2 correlated positively with leukocyte transendothelial migration, but negatively with aerobic metabolism, including oxidative phosphorylation. Results in Tumor and Immune System Interaction Database showed that TGFß2 correlated with the infiltration of tumor-associated macrophages (TAMs), which could be attributed to that TGFß2 promote CCL2 expression in PAAD. Moreover, correlation analysis showed that TGFß2 could trigger cancer-associated fibroblasts (CAFs) activation in PAAD. The drug sensitivity analysis may indicate that patients with TGFß2 high expression have higher sensitivity to chemotherapeutics, but the sensitivity to targeted drugs is still controversial. TGFß2 could promote expansion of CAFs and infiltration of TAMs, thus participating in the construction of a fibrotic and immunosuppressive TME in PAAD. Targeting TGFß2 could be a promising therapeutic approach, which needs to be elucidated by clinical and experimental evidences.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.