Telehealth With Comprehensive Live-Fed Real-World Data as a Patient Care Platform for Lung Cancer: Implementation and Evaluation Study.

BACKGROUND: Telehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared. The feasibility and usability of such a telehealth platform, with comprehensive, real-world data via a live feed, for cancer patient care are yet to be studied. OBJECTIVE: The primary purpose of this study is to understand the feasibility and usability of cancer patient care using a telehealth platform with longitudinal, real-world data via a live feed as a supplement to hospital electronic medical record systems specifically from physician's perspective. METHODS: A telehealth platform was constructed and launched for both physicians and patients. Real-world data were collected and curated using a comprehensive data model. Physician activities on the platform were recorded as system logs and analyzed. In February 2023, a survey was conducted among the platform's registered physicians to assess the specific areas of patient care and to quantify their before and after experiences, including the number of patients managed, time spent, dropout rate, visit rate, and follow-up data. Descriptive and inferential statistical analyses were performed on the data sets. RESULTS: Over a period of 15 months, 16,035 unique users (13,888 patients, 1539 friends and family members, and 174 physician groups with 608 individuals) registered on the platform. More than 382,000 messages including text, reminders, and pictures were generated by physicians when communicating with patients. The survey was completed by 78 group leaders (45% of the 174 physician groups). Of the participants, 84% (65.6/78; SD 8.7) reported a positive experience, with efficient communication, remote supervision, quicker response to questions, adverse event prevention, more complete follow-up data, patient risk reduction, cross-organization collaboration, and a reduction in in-person visits. The majority of the participants (59/78, 76% to 76/78, 97.4%) estimated improvements in time spent, number of patients managed, the drop-off rate, and access to medical history, with the average ranging from 57% to 105%. When compared with prior platforms, responses from physicians indicated better experiences in terms of time spent, the drop-off rate, and medical history, while the number of patients managed did not significantly change. CONCLUSIONS: This study suggests that a telehealth platform, equipped with comprehensive, real-world data via a live feed, is feasible and effective for cancer patient care. It enhances inpatient management by improving time efficiencies, reducing drop-off rates, and providing easy access to medical history. Moreover, it fosters a positive experience in physician-patient interactions.

18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway.

Oxidative stress causes gut dysfunction and is a contributing factor in several intestinal disorders. Intestinal epithelial cell survival is essential for maintaining human and animal health under oxidative stress. 18beta-Glycyrrhetinic acid (GA) is known to have multiple beneficial effects, including antioxidant activity; however, the underlying molecular mechanisms have not been well established. Thus, the present study evaluated the therapeutic effects of GA on H2O2-induced oxidative stress in intestinal porcine epithelial cells. The results showed that pretreatment with GA (100 nM for 16 h) significantly increased the levels of several antioxidant enzymes and reduced corresponding intracellular levels of reactive oxidative species and malondialdehyde. GA inhibited cell apoptosis via activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as confirmed by RNA sequencing. Further analyses demonstrated that GA upregulated the phosphorylation levels of PI3K and Akt and the protein level of B cell lymphoma 2, whereas it downregulated Cytochrome c and tumor suppressor protein p53 levels. Moreover, molecular docking analysis predicted the binding of GA to Vasoactive intestinal peptide receptor 1, a primary membrane receptor, to activate the PI3K/Akt signaling pathway. Collectively, these results revealed that GA protected against H2O2-induced oxidative damage and cell apoptosis via activating the PI3K/Akt signaling pathway, suggesting the potential therapeutic use of GA to alleviate oxidative stress in humans/animals.

Effects of after school exercise service on physical fitness in primary school students / 中国学校卫生

Objective@#To investigate the effects of after school exercise service (referred to as the "after school ES") on physical health, so as to provide evidence for possible beneficial effect of after school ES.@*Methods@#Students in the fourth grade of primary school were recruited from September 2021 to July 2022 in Changsha City and divided into the control group ( n =220) and the after school ES group ( n =220). The control group only participated in the regular physical education activities of the school. The after school ES group received after school ES for one academic year, 4 times a week, 40-50 minutes per time, for a total of 32 weeks. Body shape indicators such as height, weight and percentage of body fat, as well as physical fitness indicators such as 50 meter running, grip strength and progressive aerobic cardiovascular endurance run (PACER) were measured in September to October 2021 and June to July 2022, respectively. Independent sample t-test, Chi square test and two factors repeated measurement analysis of variance were used for statistical analysis of the data.@*Results@#After one academic year, compared with the control group [(13.52±2.30)kg], muscle mass of primary school students in the after school ES group [(13.76±2.32)kg] significantly increased, while waist to hip ratio [(0.95±0.16)] and percentage of body fat [(20.17±7.43)%] significantly decreased compared to the control group [(1.01±0.21), (22.02±12.34)%]( F=330.70, 6.85, 4.33, P <0.05). The proportion of overweight and obesity in after school ES group decreased significantly from 19.5% to 12.3% ( χ 2=4.35, P <0.05). Compared with the control group, the scores of 50 meter running [(10.00±1.06, 10.21±0.83)s], 1 minute sit up [(33.25±8.24, 30.76±9.34)times], sitting and flexion [(14.53±7.50, 8.59±6.32)cm], 1 minute rope skipping [(125.01±30.50, 115.97±32.09)times], eyes closed and single legged standing [(30.00±34.72, 25.72±23.82)s], selective response time [(635.66±91.72, 652.79±120.42)ms] and VO 2max [(45.31± 1.02 , 43.67±0.85)mL/(kg〖 ·min)] in the after school ES group were significantly improved, with statistical significance ( F= 5.32 , 443.14, 97.23, 814.07, 36.49, 6.11, 396.91, P <0.05).@*Conclusions@#After school ES can improve body shape of primary school students, reduce the risk of overweight and obesity and enhance physical fitness. It is recommended that schools should appropriately increase after school ES to promote physical fitness of students.

Prognostic significance of CDK6 amplification in esophageal squamous cell carcinoma.

Dysregulation of CDK6 plays crucial roles in the carcinogenesis of many kinds of human malignancies. However, the role of CDK6 in esophageal squamous cell carcinoma (ESCC) is not well known. We investigated the frequency and prognostic value of CDK6 amplification to improve the risk stratification in patients with ESCC. Pan-cancer analysis of CDK6 was conducted on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. CDK6 amplification was detected in 502 ESCC samples by Fluorescence in situ hybridization (FISH) through tissue microarrays (TMA). Pan-cancer analysis revealed that CDK6 mRNA level was much higher in multiple kinds of cancers and higher CDK6 mRNA level indicated a better prognosis in ESCC. In this study, CDK6 amplification was detected in 27.5% (138/502) of patients with ESCC. CDK6 amplification was significantly correlated with tumor size (p = 0.044). Patients with CDK6 amplification tended to have a longer disease-free survival (DFS) (p = 0.228) and overall survival (OS) (p = 0.200) compared with patients without CDK6 amplification but of no significance. When further divided into I-II and III-IV stage, CDK6 amplification was significantly associated with longer DFS and OS in III-IV stage group (DFS, p = 0.036; OS, p = 0.022) rather than in I-II stage group (DFS, p = 0.776; OS, p = 0.611). On univariate and multivariate analysis of Cox hazard model, differentiation, vessel invasion, nerve invasion, invasive depth, lymph node metastasis and clinical stage were significantly associated with DFS and OS. Moreover, invasion depth was an independent factor for ESCC prognosis. Taken together, for ESCC patients in III-IV stage, CDK6 amplification indicated a better prognosis.

Lip cyanosis as the first symptom of Leigh syndrome associated with mitochondrial complex I deficiency due to a compound heterozygous NDUFS1 mutation: A case report.

BACKGROUND: Leigh syndrome (LS) is a rare, progressive, and fatal neurodegenerative disease that occurs mainly in infants and children. Neonatal LS has not yet been fully described. METHODS: The study design was approved by the ethics review board of Shenzhen Children's Hospital. RESULTS: A 24-day-old full-term male infant presented with a 2-day history of lip cyanosis when crying in September 2021. He was born to nonconsanguineous Asian parents. After birth, the patient was fed poorly. A recurrent decrease in peripheral oxygen saturation and difficulty in weaning from mechanical ventilation during hospitalization were observed. There were no abnormalities on brain magnetic resonance imaging (MRI) or blood and urine organic acid analyses on admission. His lactic acid level increased markedly, and repeat MRI showed symmetrical abnormal signal areas in the bilateral basal ganglia and brainstem with disease progression. Trio whole-exome sequencing revealed 2 heterozygous mutations (c.64C > T [p.R22X] and c.584T > C [p.L195S]) in NDUFS1. Based on these findings, mitochondrial respiratory chain complex I deficiency-related LS was diagnosed. The patient underwent tracheal intubation and mechanical ventilation for respiratory failure. His oxygen saturation levels were maintained at normal levels with partially assisted ventilation. He was administered broad-spectrum antibiotics, oral coenzyme Q10, multivitamins, and idebenone. During hospitalization, the patient developed progressive consciousness impairment and respiratory and circulatory failure. He died on day 30. CONCLUSION: Lip cyanosis is an important initial symptom in LS. Mild upper respiratory tract infections can induce LS and aggravate the disease. No abnormal changes in the brain MRI were observed in the early LS stages in this patient. Multiple MRIs and blood lactic acid tests during disease progression and genetic testing are important for prompt and accurate diagnosis of LS.

Identification and evaluation of circulating small extracellular vesicle microRNAs as diagnostic biomarkers for patients with indeterminate pulmonary nodules.

BACKGROUND: The identification of indeterminate pulmonary nodules (IPNs) following a low-dose computed tomography (LDCT) is a major challenge for early diagnosis of lung cancer. The inadequate assessment of IPNs' malignancy risk results in a large number of unnecessary surgeries or an increased risk of cancer metastases. However, limited studies on non-invasive diagnosis of IPNs have been reported. METHODS: In this study, we identified and evaluated the diagnostic value of circulating small extracellular vesicle (sEV) microRNAs (miRNAs) in patients with IPNs that had been newly detected using LDCT scanning and were scheduled for surgery. Out of 459 recruited patients, 109 eligible patients with IPNs were enrolled in the training cohort (n = 47) and the test cohort (n = 62). An external cohort (n = 99) was used for validation. MiRNAs were extracted from plasma sEVs, and assessed using Small RNA sequencing. 490 lung adenocarcinoma samples and follow-up data were used to investigate the role of miRNAs in overall survival. RESULTS: A circulating sEV miRNA (CirsEV-miR) model was constructed from five differentially expressed miRNAs (DEMs), showing 0.920 AUC in the training cohort (n = 47), and further identified in the test cohort (n = 62) and in an external validation cohort (n = 99). Among five DEMs of the CirsEV-miR model, miR-101-3p and miR-150-5p were significantly associated with better overall survival (p = 0.0001 and p = 0.0069). The CirsEV-miR scores were calculated, which significantly correlated with IPNs diameters (p < 0.05), and were able to discriminate between benign and malignant PNs (diameter ≤ 1 cm). The expression patterns of sEV miRNAs in the benign, adenocarcinoma in situ/minimally invasive adenocarcinoma, and invasive adenocarcinoma subgroups were found to gradually change with the increase in aggressiveness for the first time. Among all DEMs of the three subgroups, five miRNAs (miR-30c-5p, miR-30e-5p, miR-500a-3p, miR-125a-5p, and miR-99a-5p) were also significantly associated with overall survival of lung adenocarcinoma patients. CONCLUSIONS: Our results indicate that the CirsEV-miR model could help distinguish between benign and malignant PNs, providing insights into the feasibility of circulating sEV miRNAs in diagnostic biomarker development. TRIAL REGISTRATION: Chinese Clinical Trials: ChiCTR1800019877. Registered 05 December 2018, https://www.chictr.org.cn/showproj.aspx?proj=31346 .

Acute high intensity interval exercise is similarly effective as moderate intensity continuous exercise on plasma glucose control in type 2 diabetic men aged 30 to 50 years: a randomized controlled trial.

BACKGROUND: The aim of this study was to compare the acute effects of high-intensity interval exercise (HIIE) versus moderate-intensity continuous exercise (MICE) on postprandial plasma glucose and insulin concentrations in men aged 30-50 years with type 2 diabetes (T2D), hoping to provide empirical evidence for the effects of different exercise types on glucose management in T2D patients. METHODS: Fourteen men with type 2 diabetes (T2D) underwent a randomized three crossover intervention: HIIE with cycling; energy expenditure matched MICE with cycling; and a sedentary control [CON]) in postprandial state. Plasma glucose and insulin levels were measured at pre-exercise, postexercise, 1 h postexercise, prelunch and 1 h postlunch, respectively. Responses of areas under the curve (AUC) during 4 h from pre-exercise to 1 h postlunch were also calculated. RESULTS: Both HIIE and MICE decreased plasma glucose and insulin levels during 4 h experimental period compared to CON, with significant intervention × time interaction effects for glucose (P=0.001) and insulin (P=0.006) values evolution. Area under curve (AUCs) for glucose and insulin were reduced in HIIE and MICE compared to CON (P<0.05), whereas no differences were found between HIIE and MICE. CONCLUSIONS: Acute HIIE and the matched MICE improve plasma glucose control in the same magnitude in type 2 diabetic men aged 30-50 years.

The association between diabetes status and latent-TB IGRA levels from a cross-sectional study in eastern China.

Background: There is a debate regarding the sensitivity of the QuantiFERON-TB Gold In-Tube (QFT) among people with diabetes, and prior studies have shown heterogeneous results. We evaluated whether the QFT TB antigen was modified among persons with differing diabetes status and other related risk factors. Methods: A cross-sectional study of 5,302 people was conducted to screen latent tuberculosis infection (LTBI) in eastern China. The QFT assay was performed as an indicator of LTBI. Fasting plasma glucose (FPG) was collected from each participant; the definition of diabetes followed the guidelines from the American Diabetes Association. Participants were classified into normoglycemia, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes to evaluate the relationship between the QFT TB antigen and distinct diabetes status. Results: TB antigen values from the QFT were statistically different among participants with differing diabetes status (P = 0.008). Persons with undiagnosed diabetes had a higher TB antigen value (0.96 ± 0.20) than persons with normoglycemia (0.50 ± 0.02, P < 0.05). However, the TB antigen values demonstrated no significant difference among the four different diabetic groups when stratified by the standard cutoff for the QFT (P = 0.492 for the positive group and P = 0.368 for the negative group). In a linear regression model, we found that FPG, age, and smoking were positively associated with the QFT TB antigen value (P = 0.017, P < 0.001, and P < 0.001). Conclusions: Diabetes status had little influence on the level of QFT TB antigen response among IGRA-positive persons. However, FPG, old age, and smoking were important risk factors for increasing levels of QFT TB antigen.

The Combination of Radiotherapy With Immunotherapy and Potential Predictive Biomarkers for Treatment of Non-Small Cell Lung Cancer Patients.

Radiotherapy is an effective local treatment modality of NSCLC. Its capabilities of eliminating tumor cells by inducing double strand DNA (dsDNA) damage and modulating anti-tumor immune response in irradiated and nonirradiated sites have been elucidated. The novel ICIs therapy has brought hope to patients resistant to traditional treatment methods, including radiotherapy. The integration of radiotherapy with immunotherapy has shown improved efficacy to control tumor progression and prolong survival in NSCLC. In this context, biomarkers that help choose the most effective treatment modality for individuals and avoid unnecessary toxicities caused by ineffective treatment are urgently needed. This article summarized the effects of radiation in the tumor immune microenvironment and the mechanisms involved. Outcomes of multiple clinical trials investigating immuno-radiotherapy were also discussed here. Furthermore, we outlined the emerging biomarkers for the efficacy of PD-1/PD-L1 blockades and radiation therapy and discussed their predictive value in NSCLC.

Investigating efficacy of "microbiota modulation of the gut-lung Axis" combined with chemotherapy in patients with advanced NSCLC: study protocol for a multicenter, prospective, double blind, placebo controlled, randomized trial.

BACKGROUND: Most NSCLCs metastasised out of the lungs at the time of diagnosis and cannot be surgically removed . Cytotoxic chemotherapy drugs have become the main treatment in recent decades, especially in patients with NSCLC without EGFR, ALK, and ROS gene mutations. The prognosis of lung cancer is poor, and the overall 5-year survival rate is only 9-13%. Therefore the treatment of advanced NSCLC remains a significant medical need. Recent studies have shown a significant relationship between the gut-lung axis microecology and malignant tumors. Intestinal probiotics are likely to play a role in inhibiting tumorigenesis through "intestinal-pulmonary axis microecological regulation". This study will seek to investigate the efficacy of "Microbiota modulation of the Gut-Lung Axis" combined with chemotherapy in patients with advanced NSCLC. METHODS: The research is a multicenter, prospective, double blind, placebo controlled, randomized trial. Based on the theoretical basis of "intestinal and lung axis microecological adjustment", combined with traditional platinum-containing two-drug chemotherapy, the efficacy of the new therapy on patients with advanced NSCLC was observed. Collect the basic information of the patient, and study the effect of platinum-based combined chemotherapy on the diversity of intestinal flora in patients with lung cancer after receiving chemotherapy treatment, feces before and after chemotherapy, and the status and extent of adverse reactions during chemotherapy . A total of 180 subjects were included, divided into a control group (platinum-containing dual-drug chemotherapy) and an intervention group (platinum-containing dual-drug chemotherapy combined with Bifico), and were randomly assigned to the group 1:1. DISCUSSION: As a result, intestinal-pulmonary microecological balance could become a new target for the treatment of lung cancer. This study explores the combination of intestinal microecological regulation and chemotherapy to provide new treatment strategies and basis for lung cancer patients. It can help prolong the survival time of lung cancer patients and improve the quality of life, thereby generating huge economic and social benefits. The results can be promoted and applied to units engaged in the treatment of lung cancer. TRIAL REGISTRATION NUMBER: NCT03642548, date: August 22, 2018, the first version protocol. The URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03642548?term=NCT03642548&draw=2&rank=1 .

Prognostic value and characterization of NTRK1 variation by fluorescence in situ hybridization in esophageal squamous cell carcinoma.

PURPOSE: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC). METHODS: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Kaplan-Meier curves with log-rank tests were used to evaluate survival. RESULTS: We identified 8 (1.5%), 35(6.7%) and 109 (20.8%) cases with a NTRK1 rearrangement using 15%, 10% and 5% as cut-off values, respectively. We observed copy number (CN) variation of NTRK1 in some cases: 79 (15.1%) cases had a gain in NTRK1 CN ≥ 3, and 24 (4.6%) cases had NTRK1 CN ≥ 4. A NTRK1 rearrangement at the above-mentioned thresholds was not related to disease-free survival (DFS, P = 0.45, 0.47, 0.87) and overall survival (OS, P = 0.80, 0.74, 0.57), respectively. Gain in NTRK1 CN was associated with a poor prognosis irrespective of whether NTRK1 CN ≥ 4 (DFS, P = 0.015; OS, P = 0.035) or NTRK1 CN ≥ 3 (DFS, P = 0.039; OS, P = 0.025). CONCLUSION: A NTRK1 rearrangement occurred rarely in ESCC. The increased CN of NTRK1 might be a prognostic indicator for DFS and OS in patients with ESCC.

Comprehensive genomic profiling of combined small cell lung cancer.

BACKGROUND: Combined small cell lung cancer (CSCLC) is an uncommon and heterogeneous subtype of small cell lung cancer (SCLC). However, there is limited data concerning the different molecular changes and clinical features in CSCLC compared to pure SCLC. METHODS: The clinical and pathological characteristics of pure SCLC and CSCLC patients were analyzed. Immunohistochemistry and microdissection were performed to isolate the CSCLC components. Further molecular analysis was carried out by next-generation sequencing (NGS) in 12 CSCLC and 30 pure SCLC. RESULTS: There were no significant differences in clinical features between CSCLC and pure SCLC. Overall survival (OS) of CSCLC patients was worse than pure SCLC (P=0.005). NGS results indicated that TP53 and RB1 were the most frequently mutated genes in both CSCLC (83.33% and 66.67%) and pure SCLC (80.00% and 63.33%) groups. However, less than 10% common mutations were found in both CSCLC and pure SCLC. When analyzing the data of SCLC and non-small cell lung cancer (NSCLC) components of CSCLC, more than 50% common mutations, and identical genes with mutations were detected. Moreover, there were also common biological processes and signaling pathways identified in CSCLC and pure SCLC, in addition to SCLC and NSCLC components. CONCLUSIONS: There were no significant differences in terms of clinical features between CSCLC and pure SCLC. However, the prognosis for CSCLC was worse than pure SCLC. NGS analysis suggested that CSCLC components might derive from the same pluripotent single clone with common initial molecular alterations and subsequent acquisitions of other genetic mutations.

Virological activity in treatment-naïve HBeAg-negative HBV-infected adult patients: A community-based study in Jiangsu, China.

Nowadays most of the hepatitis B virus (HBV) infected population are adults, among which hepatitis B e antigen (HBeAg) negative infection occupied the largest proportion of HBV infection in China. HBeAg-negative patients are heterogeneous, and the corresponding interventions are different. Therefore, it is worth researching the infection characteristics of HBeAg-negative patients to help guide the interventions.A total of 11,738 treatment-naïve HBeAg-negative adult patients were randomly selected, and their demographic and medical history information were collected. The liver biochemistry, and HBV infection biomarkers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), HBeAg, hepatitis B e antibody (anti-HBe), hepatitis B core antibody (anti-HBc), and hepatitis B virus deoxyribonucleic acid (HBV-DNA) levels were tested. The infection characteristics and their influencing factors were explored.Sixty percent of the patients presented HBV-DNA-positive, of which 31.2% had HBV-DNA level higher than 2000 IU/mL, and 16.5% had HBV-DNA level higher than 20,000 IU/mL. HBV-DNA levels tended to increase along with the increasing of age, and the male patients had significant higher HBV-DNA levels than the female patients. Twenty-four percent of the patients had abnormal transaminase. The male patients were more vulnerable to abnormal transaminase (30.0%) than the female patients (18.4%). Fifty-five percent patients with HBV-DNA ≥20,000 IU/mL presented abnormal alanine aminotransferase (ALT) or aspartate transaminase (AST), which was significantly higher than that of patients with HBV-DNA levels below 20,000 IU/mL (19.0-21.7%). Multivariate logistic regression analyses revealed that the male patients and the patients with higher viral load had higher risk of having abnormal liver function.A considerable number of HBeAg-negative patients were virological active and had liver damage. It is necessary and urgent to carry out regular active interventions for the chronic HBV-infected patients.

Long-Term Exercise Alters the Profiles of Circulating Micro-RNAs in the Plasma of Young Women.

Objective: The objective of this paper was to study the effects of long-term exercise on circulating microRNAs (miRNAs) in human plasma. Methods: Whole blood was collected from 10 female elite athletes with at least 5 years of training experience in a Synchronized Swimming Group (S group) and 15 female college students without regular exercise training (C group). Plasma miRNAs were then isolated, sequenced, and semi-quantified by the second-generation sequencing technology, and the results were analyzed by bioinformatics methods. Results: We found 380 differentially expressed miRNAs in the S group compared with the C group, among which 238 miRNAs were upregulated and 142 were downregulated. The top five abundant miRNAs in the 380 miRNAs of the S group are hsa-miR-451a, hsa-miR-486, hsa-miR-21-5p, hsa-miR-423-5p, and hsa-let-7b-5p. Muscle-specific/enriched miRNAs were not significantly different, except for miR-206 and miR-486. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, a large proportion of the differentially expressed miRNAs are targeted in cancer-related pathways, including proteoglycans in cancer and miRNAs in cancer and basal cell carcinoma. As the levels of circulating miRNAs (ci-miRNAs) are commonly known to be significantly deregulated in cancer patients, we further compared the levels of some well-studied miRNAs in different types of cancer patients with those in the S group and found that long-term exercise regulates the level of ci-miRNAs in an opposite direction to those in cancer patients. Conclusion: Long-term exercise significantly alters the profiles of plasma miRNAs in healthy young women. It may reduce the risk of certain types of cancers by regulating plasma miRNA levels.

Adjuvant Chemotherapy with Chinese Herbal Medicine Formulas Versus Placebo in Patients with Lung Adenocarcinoma after Radical Surgery: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: The toxicity and side effects caused by adjuvant chemotherapy (ACT) after radical surgery for lung adenocarcinoma (LAC) lead to early termination frequently. This study was conducted to provide an objective basis for the effect of Chinese herbal medicine formulas (CHMFs) combined with chemotherapy in reducing toxicity and enhancing efficacy of ACT. METHOD: From February 17th, 2012 to March 20th, 2015, 233 patients from 7 hospitals diagnosed with LAC in IB~IIIA stage were randomly assigned into ACT + CHMF group (116 patients) and ACT + placebo group (117 patients). CHMF was taken orally until the end of chemotherapy. Chemotherapy-related toxic, side effects were investigated as the primary outcome. Disease-free survival (DFS) and overall survival (OS) were used as the secondary outcome. RESULTS: At one week following chemotherapy, the incidence of dry mouth, diarrhea and thrombocytopenia significantly decreased in CHMF group (P = 0.017, P = 0.033, P = 0.019, respectively). At two weeks following chemotherapy, fatigue and diarrhea were more obvious in the placebo group (P = 0.028, P = 0.025, respectively). In addition, patients in the CHMF group showed an increase in median DFS from 37.1 to 51.5 months compared with placebo group although there was no statistical significance (P = 0.16). In the stage IB subgroup, the CHMF group had a significantly better DFS (HR (95% CI) = 0.53 (0.28-0.99), P = 0.046). There was no significant difference in OS between the groups (P = 0.72). CONCLUSION: For patients with LAC, ACT combined with CHMF after radical surgery can prolong the DFS time especially in the early stage, and reduces the chemotherapy-related toxic and side effects. TRIAL REGISTRATION: NCT01441752. Registered 14 July, 2011.

Effects of Living High-Training Low and High on Body Composition and Metabolic Risk Markers in Overweight and Obese Females.

This study examined the effects of 4 weeks of living high-training low and high (LHTLH) under moderate hypoxia on body weight, body composition, and metabolic risk markers of overweight and obese females. Nineteen healthy overweight or obese females participated in this study. Participants were assigned to the normoxic training group (NG) or the LHTLH group (HG). The NG participants lived and trained at sea level. The HG participants stayed for approximately 10 hours in a simulated 2300 m normobaric state of hypoxia for six days a week and trained for 2 hours 3 times a week under the same simulated hypoxia. The interventions lasted for 4 weeks. All groups underwent dietary restriction based on resting metabolic rate. The heart rate of the participants was monitored every ten minutes during exercise to ensure that the intensity was in the aerobic range. Compared with the preintervention values, body weight decreased significantly in both the NG and the HG (-8.81 ± 2.09% and -9.09 ± 1.15%, respectively). The fat mass of the arm, leg, trunk, and whole body showed significant reductions in both the NG and the HG, but no significant interaction effect was observed. The percentage of lean soft tissue mass loss in the total body weight loss tended to be lower in the HG (27.61% versus 15.94%, P=0.085). Between the NG and the HG, significant interaction effects of serum total cholesterol (-12.66 ± 9.09% versus -0.05 ± 13.36%,) and apolipoprotein A1 (-13.66 ± 3.61% versus -5.32 ± 11.07%, P=0.042) were observed. A slight increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the HG (1.12 ± 12.34%) but a decrease was observed in the NG (-11.36 ± 18.91%). The interaction effect of HDL-C between NG and HG exhibited a significant trend (P=0.055). No added effects on serum triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), or APO-B were observed after 4 weeks of LHTLH. In conclusion, 4 weeks of LHTLH combined with dietary restriction could effectively reduce the body weight and body fat mass of overweight and obese females. Compared with training and sleeping under normoxia, no additive benefit of LHTLH on the loss of body weight and body fat mass was exhibited. However, LHTLH may help to relieve the loss of lean soft tissue mass and serum HDL-C.

Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: To determine the clinical activity and safety of Chinese herbal medicine (CHM) combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in patients with advanced pulmonary adenocarcinoma (ADC) and the ability of CHM combined with EGFR-TKI to activate EGFR mutations. Methods: Three hundred and fifty-four patients were randomly assigned to EGFR-TKI (erlotinib 150 mg/d, gefitinib 250 mg/d, or icotinib 125 mg tid/d) plus CHM (TKI+CHM, N = 185) or EGFR-TKI plus placebo (TKI+placebo, N = 169). Progression-free survival (PFS) was the primary end point; the secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life [Functional Assessment of Cancer Therapy-Lung (FACT-L) and Lung Cancer Symptom Scale (LCSS)], and safety. Results: The median PFS was significantly longer for the TKI+CHM group (13.50 months; 95% CI, 11.20-16.46 months) than with the EGFR-TKI group (10.94 months; 95% CI, 8.97-12.45 months; hazard ratio, 0.68; 95% CI, 0.51-0.90; P = 0.0064). The subgroup analyses favored TKI+CHM as a first-line treatment (15.97 vs. 10.97 months, P = 0.0447) rather than as a second-line treatment (11.43 vs. 9.23 months, P = 0.0530). Patients with exon 19 deletion had a significantly longer PFS than with 21 L858R. The addition of CHM to TKI significantly improved the ORR (64.32% vs. 52.66%, P = 0.026) and QoL. Drug-related grade 1-2 adverse events were less common with TKI+CHM. Conclusions: TKI+CHM improved PFS when compared with TKI alone in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01745302.

Ultrasound-controlled DOX-SiO2 nanocomposites enhance the antitumour efficacy and attenuate the toxicity of doxorubicin.

The toxicity of doxorubicin (DOX), especially in terms of cardiotoxicity, has been a common problem in its clinical use. In our studies, we synthesized and characterized DOX-SiO2 nanocomposites. In the in vitro experiments, DOX-SiO2 nanocomposites could more effectively induce apoptosis, inhibit colony formation, and inhibit the proliferation of the cancer cell line HeLa compared with free DOX. Furthermore, ultrasound could dramatically enhance these abilities of DOX-SiO2 nanocomposites. The in vivo studies showed that DOX-SiO2 nanocomposites increased the concentration of DOX in the tumour region and decreased the concentration of DOX in normal tissues. Additionally, DOX-SiO2 nanocomposites under ultrasound could inhibit growth and increase the apoptosis of xenograft tumour cells more effectively than DOX-SiO2 nanocomposites alone. Meanwhile, the cardiotoxicity of DOX was significantly reduced by DOX-SiO2 nanocomposites. The difference was more obvious in DOX-SiO2 nanocomposites under ultrasound. Moreover, prolonging the ultrasound time augments the antitumour efficacy and attenuates the toxicity of DOX-SiO2 nanocomposites. In summary, we concluded that DOX-SiO2 nanocomposites under ultrasound decrease DOX-induced toxicity in normal tissues and increase the antitumour effect of DOX by targeted delivery and controllable release, which shows the great potential of DOX-SiO2 nanocomposites for the delivery of DOX in the clinic.

Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study.

BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known. METHODS: A population-based cohort of adult CHB patients without a history of alcohol drinking or NAFLD were recruited and followed up from October 2012 to January 2015 in Jiangsu province, China. Using Cox proportional hazards regression model, potential risk factors including viral and metabolic factors for NAFLD were evaluated. RESULTS: Two thousand three hundred and ninety-three adult CHB patients (mean age 50.7 ± 13.2 years) were included in the cohort. With 4429 person-years of follow-up, 283 individuals progressed to NAFLD with an incidence rate of 63.89/1000 person-years. Overweight and obese CHB patients had an increased risk of NAFLD (overweight adjusted hazard ratio [HR], 3.10; 95% CI, 2.29-4.18; obese HR, 8.52; 95%CI, 5.93-12.25) compared to normal weight carriers. The incidence of NAFLD was associated with concurrent type 2 diabetes mellitus (DM) (HR, 1.88; 95%CI, 1.15-3.08). However, no associations between viral factors with NAFLD incidence rate were identified. In a subgroup of participants with concurrent type 2 DM, detectable HBV DNA levels were negatively associated with the development of NAFLD (HR, 0.37; 95%CI, 0.14-0.98). There was super-multiplicative interaction between BMI and gender with respect to incidence of NAFLD, with an ROR of 2.08 (95%CI, 1.02-4.23). CONCLUSION: Metabolic factors play an important role in the presence of NAFLD among Chinese CHB patients. However, viral replication factors are not related to NAFLD except among those with concurrent type 2 DM.