Oxygen self-supplying small size magnetic nanoenzymes for synergistic photodynamic and catalytic therapy of breast cancer.

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic-photodynamic combination therapy.

Can ChatGPT Provide Quality Information on Integrative Oncology? A Brief Report.

This short report evaluated the accuracy and quality of information provided by ChatGPT regarding the use of complementary and integrative medicine for cancer. Using the QUality Evaluation Scoring Tool, a panel of 12 reviewers assessed ChatGPT's responses to 8 questions. The study found that ChatGPT provided moderate-quality responses that were relatively unbiased and not misleading. However, the chatbot's inability to reference specific scientific studies was a significant limitation. Patients with cancer should not rely on ChatGPT for clinical advice until further systematic validation. Future studies should examine how patients perceive ChatGPT's information and its impact on communication with health care professionals.

Association between potential supplement-drug interactions and liver diseases in patients with cancer: A large prospective cohort study.

BACKGROUND & AIMS: The concurrent use of herbal and dietary supplements and conventional drugs can lead to interactions in patients with cancer, of which hepatotoxicity is one of the most concerning sequelae. This study examined the potential supplement-drug interactions involving the hepatic system, and their associations with documented liver diseases, among patients with cancer in a large population-based cohort in the UK Biobank. METHODS: Participants diagnosed with cancer and had completed supplement-use assessment after diagnosis were included. Potentially interacting supplement-drug combinations that involved CYP enzymes or increased the risk of hepatotoxicity were identified from four tertiary databases. Liver diseases were identified using ICD-codes K70-77. Log-binomial regression was used to investigate the associations between potentially-interacting supplement-drug combinations and liver diseases documented (1) at any time, and (2) confined to only after the time of supplement-use assessment, adjusting for age, sex and pre-existing comorbidities. RESULTS: This analysis included 30,239 participants (mean age = 60.0 years; 61.9% female). Over half (n = 17,698, 58.5%) reported the use of supplements after cancer diagnoses. Among supplements users, 36.9% (n = 6537/17,698) were on supplement-drug combinations with interacting potential involving the hepatic system. Patients taking supplements and drugs who had hepatic comorbidities were more likely to take potentially interacting pairs (adjusted risk ratio = 1.14, 95% CI = 1.06-1.23, p < 0.001). However, no significant association was observed between the use of these combinations and subsequent liver diseases (all p > 0.05). CONCLUSION: Approximately one-third of the participants who had cancer and were supplement users had a risk of potential supplement-drug interactions that contribute to adverse liver effect. Healthcare professionals should communicate with patients with cancer, especially those with pre-existing liver diseases, about supplement use and proactively assess the clinical significance of potential interactions.

Association between dietary supplement use and mortality among US adults with diabetes: a longitudinal cohort study.

BACKGROUND: Despite the popularity of dietary supplements, their effectiveness and safety in patients with diabetes remain controversial. Furthermore, evidence from clinical trials may not be generalizable to real-world settings. This study examined the association between dietary supplement use and mortality outcomes among patients with diabetes based on a nationally representative sample of US adults. METHODS: This study analyzed data from National Health and Nutrition Examination Survey (NHANES) 1999-2018. Supplement users referred to adults with diabetes who reported the use of any dietary supplements in the last 30 days, and with a cumulative duration of ≥ 90 days. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between supplement use and all-cause mortality, and mortality from cardiovascular diseases (CVD), diabetes, and cancer. Subgroup analysis of different supplement classes (vitamins, minerals, botanicals, amino acids, fatty acids, probiotics and glucosamine) were also conducted. RESULTS: We included 8,122 adults with diabetes (mean age: 59.4 years; 48.7% female), of whom 3,997 (54.0%) reported using supplements regularly. Vitamins (87.3%), minerals (75.3%) and botanicals (51.8%) were the most popular supplements. At a median follow-up of 6.9 years, 2447 all-cause deaths had occurred. Overall supplement use was not associated with risk of all-cause mortality among patients with diabetes (HR = 0.97, 95% CI: 0.87 to 1.08, P = 0.56). Subgroup analyses suggested that amino acid use was associated with a lower all-cause mortality (HR = 0.66, 95% CI: 0.46 to 0.96, P = 0.028), while the use of fatty acids (HR = 0.62, 95% CI: 0.42 to 0.92, P = 0.018) and glucosamine (HR = 0.69, 95% CI: 0.51 to 0.95, P = 0.022) supplements were significantly associated with lower CVD mortality. CONCLUSIONS: Our results derived from real-world data suggested that overall supplement use was not associated with any mortality benefit in patients with diabetes. However, there is preliminary evidence that suggests a protective effect of amino acid use on all-cause mortality, and a benefit of fatty acids and glucosamine supplement use on CVD mortality. Future large-scale longitudinal studies are needed to investigate the association between dietary supplement use and other intermediate diabetes-related outcomes, such as glucose control and reducing diabetes-related complications.

The use of traditional, complementary and integrative medicine in Chinese adolescent and young adult patients with cancer: A multicenter cross-sectional study.

PURPOSE: Adolescent and young adult (AYA) patients with cancer often experience unique physical and psychosocial complications. They may turn to traditional, complementary and integrative medicines (TCIM) to address these concerns. To examine the pattern of TCIM use among AYA patients with cancer and explored their preferences regarding TCIM education. METHODS: Between August 2021 and December 2022, 246 patients diagnosed with cancer between 15 and 39 years old were recruited from hospitals in Hong Kong. They completed a structured questionnaire on TCIM use, symptom burden, psychological status and preference on education content. Multivariable logistic regression was used to identify predictors of TCIM use, adjusting for age and sex. RESULTS: Overall, 60.2% reported TCIM use, most commonly vitamins (24.0%) and Chinese herbal medicine (22.0%). The most common reasons for using TCIM were to improve general health (70.9%) and manage chronic symptoms (33.1%). Among patients on active treatment, TCIM users tend to report higher anxiety symptoms (aOR = 1.13, 95% CI = 1.02-1.27). TCIM users who were post-treatment were more likely to have chronic comorbidities (aOR = 3.54, 95% CI = 1.29-11.5). AYA patients indicated that they would like TCIM information to address specific needs, particularly fatigue (53.7%) and psychological problems (54.1%). CONCLUSIONS: The use of TCIM is common among AYA patients with cancer, especially among patients with high symptom burdens. A tailored education programme should be provided based on patients' preferences and needs. Healthcare professionals including oncologists and oncology nurses should communicate with AYA patients about TCIM use and address their needs by making evidence-based referrals/recommendations based on treatment status and symptom burden.

The Use of Traditional, Complementary, and Integrative Medicine in Cancer: Data-Mining Study of 1 Million Web-Based Posts From Health Forums and Social Media Platforms.

BACKGROUND: Patients with cancer are increasingly using forums and social media platforms to access health information and share their experiences, particularly in the use of traditional, complementary, and integrative medicine (TCIM). Despite the popularity of TCIM among patients with cancer, few related studies have used data from these web-based sources to explore the use of TCIM among patients with cancer. OBJECTIVE: This study leveraged multiple forums and social media platforms to explore patients' use, interest, and perception of TCIM for cancer care. METHODS: Posts (in English) related to TCIM were collected from Facebook, Twitter, Reddit, and 16 health forums from inception until February 2022. Both manual assessments and natural language processing were performed. Descriptive analyses were performed to explore the most commonly discussed TCIM modalities for each symptom and cancer type. Sentiment analyses were performed to measure the polarity of each post or comment, and themes were identified from posts with positive and negative sentiments. TCIM modalities that are emerging or recommended in the guidelines were identified a priori. Exploratory topic-modeling analyses with latent Dirichlet allocation were conducted to investigate the patients' perceptions of these modalities. RESULTS: Among the 1,620,755 posts available, cancer-related symptoms, such as pain (10/10, 100% cancer types), anxiety and depression (9/10, 90%), and poor sleep (9/10, 90%), were commonly discussed. Cannabis was among the most frequently discussed TCIM modalities for pain in 7 (70%) out of 10 cancer types, as well as nausea and vomiting, loss of appetite, anxiety and depression, and poor sleep. A total of 7 positive and 7 negative themes were also identified. The positive themes included TCIM, making symptoms manageable, and reducing the need for medication and their side effects. The belief that TCIM and conventional treatments were not mutually exclusive and intolerance to conventional treatment may facilitate TCIM use. Conversely, TCIM was viewed as leading to patients' refusal of conventional treatment or delays in diagnosis and treatment. Doctors' ignorance regarding TCIM and the lack of information provided about TCIM may be barriers to its use. Exploratory analyses showed that TCIM recommendations were well discussed among patients; however, these modalities were also used for many other indications. Other notable topics included concerns about the legalization of cannabis, acupressure techniques, and positive experiences of meditation. CONCLUSIONS: Using machine learning techniques, social media and health forums provide a valuable resource for patient-generated data regarding the pattern of use and patients' perceptions of TCIM. Such information will help clarify patients' needs and concerns and provide directions for research on integrating TCIM into cancer care. Our results also suggest that effective communication about TCIM should be achieved and that doctors should be more open-minded to actively discuss TCIM use with their patients.

Associations of dietary supplement use with all-cause and cause-specific mortality in patients diagnosed with cancer: a large prospective cohort study in the UK Biobank.

PURPOSE: Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort. METHODS: This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities). RESULTS: This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90-0.99) and cancer (aHR = 0.89, 95% CI = 0.83-0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83-0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87-0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82-0.94) were associated with a modest decrease in cancer mortality which were marginally significant. CONCLUSIONS: This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes.

Adjuvant probiotic Bifidobacterium animalis subsp. lactis CP-9 improve phototherapeutic treatment outcomes in neonatal jaundice among full-term newborns: A randomized double-blind clinical study.

BACKGROUND: Probiotics had been used to decreased bilirubin level in neonatal jaundice (NJ) without being further studied mechanism and stratification. The intestinal pathogen Escherichia coli produced ß-glucuronidase would increase enterohepatic circulation and elevate serum bilirubin levels (SBLs) which might worsen the disease process of NJ. STUDY OBJECTIVE: We hypothesized that some probiotics could decrease bilirubin level through inhibiting the growth of E. coli. It's assumed that adjuvant probiotic intervention might accelerate the phototherapy for NJ and alleviate the severity of the NJ. Besides, it's further study the efficacy of the probiotic intervention in NJ among the full-term and preterm newborns. MATERIALS AND METHODS: Firstly, the Bifidobacterium animalis subsp. lactis CP-9 was screened for its anti-E. coli activity. Then, it was orally administered to newborns with NJ in combination with conventional phototherapy (wavelength 425-457 nm) to determine its efficacy. 83 neonatal patients whose serum bilirubinemia was at a concentration of ≥ 15 mg/dL were participated the double-blind randomized trial and conducted in the neonatal ward of China Medical University Children's Hospital (CMUCH, Taichung, Taiwan). The test was conducted in 2 groups: experimental group: phototherapy + B. animalis subsp. lactis CP-9 (n = 43; 5 × 109 CFU/capsule) and control group: phototherapy + placebo (n = 40). The SBL and total phototherapy duration were measured. RESULTS: The experimental group showed improved serum bilirubin decline rate (-0.16 ±â€…0.02 mg/dL/h; P = .009, 95% CI -0.12 to -0.2), particularly in the first 24 hour of in-hospital care, and reduced total phototherapy duration (44.82 ±â€…3.23 h; P = .011, 95% CI: 51.3-38.2) compared with the control group. Especially, probiotics had a significant therapeutic effect (serum bilirubin decline rate: -0.18 ±â€…0.02 mg/dL/h, 95% CI -0.12 to -0.23, P = .014; phototherapy duration: 43.17 ±â€…22.72 h, 95% CI 51.9-34.3, P = .019) in the low-risk subgroup (full-term newborns). CONCLUSIONS: In conclusion, B. animalis subsp. lactis CP-9 synergistically improves treatment outcomes of NJ during in-hospital phototherapy including reduced total phototherapy duration and improved serum bilirubin decline rate, particularly in full-term newborns.

Integrating Complementary Medicine Into the Care of Childhood Cancer Survivors: A Brief Report on the Preliminary Framework and Implementation of an Educational Program.

Background: Existing educational programs typically include limited information on traditional, complementary, and integrative medicine (TCIM) for survivors of childhood cancer. Objectives: This brief report presents the preliminary results of an educational program that aims to promote the safe and effective use of Chinese medicine (CM) among survivors in Hong Kong. Methods: Survivors of childhood cancer, their caregivers, and oncology practitioners were invited to participate in a program that consists of two didactic seminars and a written educational booklet that disseminated information on the use of CM. A structured questionnaire was used to evaluate participants' receptivity toward and perceived relevance of the program. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to discuss the impact of the intervention. Results: Reach: A total of 174 participants attended the seminars, and the seminar recording received over 380 views on social media platforms since April 2021. The hardcopy of the educational booklet was distributed to 43 recipients. The web-version of the booklet was sent to 67 participants and downloaded 143 times. Efficacy: The majority found that the content of the seminar useful (mean score = 5.04/6 points), especially the CM exercise (mean score = 4.88/6 points) and dietary advice (mean score = 4.99/6 points). Intention to adopt: The survivors (or their caregivers) reported that they would adopt advice on food therapies (83.3%) and traditional Chinese health exercises (55.6%) during survivorship. Conclusion: The preliminary data on patient preferences will be applied to further develop educational materials and to establish a TCIM referral network within the cancer survivor community.

Chronic Medication Use and Factors Associated With Polypharmacy Among Outpatient Pediatric Patients.

OBJECTIVE: This study aimed to determine the prevalence and predictors of chronic polypharmacy among pediatric patients in an outpatient setting. METHODS: We conducted a review of medications dispensed to patients from an outpatient pediatric facility during a 12-month period. Patients who received chronic medications (≥30 days' supply), which contained at least 1 active pharmaceutical ingredient were included in the study. Descriptive analysis was used to determine prevalence of polypharmacy while predictive factors for polypharmacy were evaluated using logistic regression. RESULTS: Our study included 3920 patients (median age, 9.9 years; IQR, 9.4) and 16,401 medications. The median number of chronic medications used among our study cohort was 2.0 (IQR, 1) with polypharmacy identified in 309 (7.9%) patients. Predictors for polypharmacy were age and the use of certain therapeutic class of medications. Patients 12 to <19 years old (OR, 6.95; 95% CI, 4.1-10.1) were more likely to require ≥5 concurrent medications compared with patients younger than 2 years of age. Use of calcium supplements (OR, 21.2; 95% CI, 11.3-39.6), Vitamin D analogues (OR, 14.3; 95% CI, 8.0-25.8), and systemic glucocorticoids (OR, 18.8; 95% CI, 10.7-33.2) were also highly associated with polypharmacy. CONCLUSIONS: Adolescents and children with chronic medical conditions who require prolonged systemic glucocorticoids, calcium, and Vitamin D supplements are at higher risk of incurring long-term polypharmacy. This subgroup of pediatric patients may be more vulnerable to the occurrence of negative outcomes resulting from the use of multiple chronic medications.

Real-world data on herb-drug interactions in oncology: A scoping review of pharmacoepidemiological studies.

BACKGROUND: The concurrent use of conventional drugs and herbal medicines is becoming popular among patients with cancer. However, the potential risk of herb-drug interactions (HDI) remains under-addressed in the literature. Previous reviews have mainly focused on the prevalence of interactions, with less attention paid to the methods used by pharmacoepidemiological studies on evaluating HDI. This scoping review aims to summarize the existing pharmacoepidemiological studies that evaluate HDI using real-world data and to identify gaps to be addressed in future research. METHODS: A comprehensive search was performed in nine English- and Chinese-language databases from their inception to May 2021. Gray literature and manual searches were conducted to identify additional studies. The recommended components of the pharmacoepidemiological studies and key findings related to HDI were summarized. The proportion (%) of patients with cancer at risk of HDI was estimated by combining data from eligible studies. RESULTS: Twenty-eight studies were included in the review. More than half of these studies were cross-sectional studies (n = 18, 64.3%), followed by retrospective cohort studies (n = 5, 17.9%) and prospective cohort studies (n = 2, 7.1%). The three cancer drugs most commonly studied for their interaction potential with herbs were tamoxifen (n = 11, 39.3%), cyclophosphamide (n = 6, 21.4%), and paclitaxel (n = 6, 21.4%). Most cross-sectional studies identified potential HDI using tertiary databases and primary literature searches. Conversely, prospective and retrospective studies mainly investigated actual clinical outcomes, such as adverse events and secondary cancer occurrences. Most interaction outcomes identified using real-world data did not lead to negative clinical consequences. Collectively, 45.4% of herbal medicine users of the included studies were found to be at risk of HDI. We infer from this review that the common limitations of these studies were limited sample size, lack of data on herbal medicine use and details of HDI, and lack of evidence of HDI. Based on the study limitations, several recommendations to enrich the data sources and optimize the study designs were proposed. CONCLUSIONS: There is a high demand for pharmacoepidemiological research on HDI, considering the increasing popularity of herbal medicine among patients with cancer. It is anticipated that emerging real-world data in this field can guide the development of safe and effective approaches to integrative oncology.

Examining patterns of traditional Chinese medicine use in pediatric oncology: A systematic review, meta-analysis and data-mining study.

BACKGROUND: Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology. OBJECTIVE: We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study. SEARCH STRATEGY: We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM." INCLUSION CRITERIA: We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment. DATA EXTRACTION AND ANALYSIS: The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms. RESULTS: The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection. CONCLUSION: There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression.

Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries. In this study, we aimed to investigate the roles of CRP in cardiac remodelling and heart failure after MI, as well as the molecular mechanisms involved. Male C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilised to determine the fibrotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and fibroblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analysed by qRT-PCR, and protein expression changes were assessed by Western blotting. Our findings revealed that CRP attenuated cardiac hypertrophy, fibrosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and fibroblast proliferation and differentiation into myofibroblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned beneficial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and fibrosis in vitro. CRP alleviates cardiac hypertrophy, fibrosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

Examining patterns of traditional Chinese medicine use in pediatric oncology: A systematic review, meta-analysis and data-mining study / 中西医结合学报

BACKGROUND@#Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.@*OBJECTIVE@#We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.@*SEARCH STRATEGY@#We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM."@*INCLUSION CRITERIA@#We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.@*DATA EXTRACTION AND ANALYSIS@#The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.@*RESULTS@#The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.@*CONCLUSION@#There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.

Use of complementary or alternative medicine and potential interactions with chronic medications among Chinese survivors of childhood cancer.

PURPOSE: This study explored the pattern of complementary or alternative medicine (CAM) use among Chinese survivors of childhood cancer and identified potential drug-CAM interactions and factors predicting CAM use. METHODS: This cross-sectional study recruited 393 survivors of childhood cancer (male, 57.8%; mean age, 17.7 [SD = 7.3] years; mean years post-treatment, 8.8 [SD = 5.0]) from a public hospital in Hong Kong. Participants reported CAM and over-the-counter medications that they used in the past year. Prescription drug data were extracted from pharmacy dispensing records. Potential interactions between concurrent CAM and chronic medications were identified from well-established CAM-drug/herb-drug interaction databases. A multivariate logistic regression was performed to analyze associations of socio-demographic and clinical factors with CAM use. RESULTS: Half (n = 205/393, 52.2%) of the participants reported the use of CAM. The most popular CAMs were traditional Chinese medicine (n = 127/205, 62.0%) and natural products (n = 114/205, 55.3%). Among the 69 survivors (33.7%) concurrently using CAM and chronic medications, one-third (n = 21/69, 30.4%) were at risk of drug-CAM interactions that are of moderate significance. Adult survivors were more likely to use CAM than pediatric survivors (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.31-4.41). Brain tumor survivors were more likely than other solid tumor survivors to use non-oral therapies (OR, 2.70; 95% CI, 1.01-7.72). CONCLUSIONS: The prevalence of CAM use among Chinese survivors of childhood cancer was high. A minority of survivors had a risk of clinically significant CAM-drug interactions. Future studies should focus on survivors' behavior and motivations for CAM use. IMPLICATIONS FOR CANCER SURVIVORS: As the concurrent use of CAM and chronic medications might result in interactions, healthcare providers should proactively identify such interactions and develop referral pathways to promote evidence-based integrative therapies for survivors.

A public survey of traditional, complementary and integrative medicine use during the COVID-19 outbreak in Hong Kong.

BACKGROUND: During COVID-19, the public actively sought non-pharmacological and self-management approaches to prevent infection. Little is known on the use of traditional, complementary and integrative medicine (TCIM) by the public as preventive measures. This study investigated the prevalence and patterns of TCIM use during the pandemic, and identified factors associated with its use among the general population in Hong Kong. METHODS: An online cross-sectional survey was conducted from November to December 2020. The survey solicited information on the respondents' sociodemographic characteristics, risk perception of the pandemic, and use of TCIM before and during the pandemic. Logistic regression analysis was conducted to determine predictors of TCIM use. RESULTS: In total, 632 responses (completion rate = 88.1%) were analyzed. TCIM was used by 44.0% of respondents during the pandemic. The most popular forms of TCIM were vitamins or other dietary supplements (n = 160, 25.3%) and Chinese herbal medicine (n = 122, 19.3%) during the pandemic. The most frequently reported indication was strengthening the immune system, especially for vitamins or other dietary supplements (n = 142/160, 88.8%). Respondents who reported using TCIM were more likely to be female (adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.29-2.59), had higher education attainment (aOR = 2.21, 95% CI = 1.39-3.59), and older-aged (age >55 years: aOR = 1.77, 95% CI = 1.04-3.02). Respondents who resided in districts with moderate to high number of confirmed COVID-19 cases (aOR = 1.60, 95% CI = 1.07-2.42) and had a higher level of risk perception (aOR = 1.04, 95% CI = 1.01-1.07) were also more likely to use TCIM. CONCLUSION: TCIM was used commonly in Hong Kong during the COVID-19 pandemic. While vaccination and social distancing remain the mainstay of controlling the pandemic, professional bodies should proactively consider public preferences and provide information regarding the effectiveness and safety of TCIM for COVID-19 prevention and treatment.

Connectivity of the Cerebello-Thalamo-Cortical Pathway in Survivors of Childhood Leukemia Treated With Chemotherapy Only.

Importance: Treatment with contemporary chemotherapy-only protocols is associated with risk for neurocognitive impairment among survivors of childhood acute lymphoblastic leukemia (ALL). Objective: To determine whether concurrent use of methotrexate and glucocorticoids is associated with interference with the antioxidant system of the brain and damage and disruption of glucocorticoid-sensitive regions of the cerebello-thalamo-cortical network. Design, Setting, and Participants: This cross-sectional study was conducted from December 2016 to July 2019 in a single pediatric cancer tertiary care center. Participants included survivors of childhood ALL who were more than 5 years from cancer diagnosis, age 8 years or older, and treated on an institutional chemotherapy-only protocol. Age-matched community members were recruited as a control group. Data were analyzed from August 2017 to August 2020. Exposure: ALL treatment using chemotherapy-only protocols. Main Outcomes and Measures: This study compared brain volumes between survivors and individuals in a community control group and examined associations among survivors of methotrexate and dexamethasone exposure with neurocognitive outcomes. Functional and effective connectivity measures were compared between survivors with and without cognitive impairment. The Rey-Osterrieth complex figure test, a neurocognitive evaluation in which individuals are asked to copy a figure and then draw the figure from memory, was scored according to published guidelines and transformed into age-adjusted z scores based on nationally representative reference data and used to measure organization and planning deficits. ß values for neurocognitive tests represented the amount of change in cerebellar volume or chemotherapy exposure associated with 1 SD change in neurocognitive outcome by z score (mm3/1 SD in z score for cerebellum, mm3/[g×hr/L] for dexamethasone and methotrexate AUC, and mm3/intrathecal count for total intrathecal count). Results: Among 302 eligible individuals, 218 (72%) participated in the study and 176 (58%) had usable magnetic resonance imaging (MRI) results. Among these, 89 (51%) were female participants and the mean (range) age was 6.8 (1-18) years at diagnosis and 14.5 (8-27) years at evaluation. Of 100 community individuals recruited as the control group, 82 had usable MRI results; among these, 35 (43%) were female individuals and the mean (range) age was 13.8 (8-26) years at evaluation. There was no significant difference in total brain volume between survivors and individuals in the control group. Survivors of both sexes showed decreased mean (SD) cerebellar volumes compared with the control population (female: 70 568 [6465] mm3 vs 75 134 [6780] mm3; P < .001; male: 77 335 [6210] mm3 vs 79 020 [7420] mm3; P < .001). In female survivors, decreased cerebellar volume was associated with worse performance in Rey-Osterrieth complex figure test (left cerebellum: ß = 55.54; SE = 25.55; P = .03; right cerebellum: ß = 52.57; SE = 25.50; P = .04) and poorer dominant-hand motor processing speed (ie, grooved pegboard performance) (left cerebellum: ß = 82.71; SE = 31.04; P = .009; right cerebellum: ß = 91.06; SE = 30.72; P = .004). In female survivors, increased number of intrathecal treatments (ie, number of separate injections) was also associated with Worse Rey-Osterrieth test performance (ß = -0.154; SE = 0.063; P = .02), as was increased dexamethasone exposure (ß = -0.0014; SE = 0.0005; P = .01). Executive dysfunction was correlated with increased global efficiency between smaller brain regions (Pearson r = -0.24; P = .01) compared with individuals without dysfunction. Anatomical connectivity showed differences between impaired and nonimpaired survivors. Analysis of variance of effective-connectivity weights identified a significant interaction association (F = 3.99; P = .02) among the direction and strength of connectivity between the cerebellum and DLPFC, female sex, and executive dysfunction. Finally, no effective connectivity was found between the precuneus and DLPFC in female survivors with executive dysfunction. Conclusions and Relevance: These findings suggest that dexamethasone exposure was associated with smaller cerebello-thalamo-cortical regions in survivors of ALL and that disruption of effective connectivity was associated with impairment of executive function in female survivors.

Tubeimoside I-induced lung cancer cell death and the underlying crosstalk between lysosomes and mitochondria.

Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-associated apoptosis in lung cancer cells. We found that Tub disrupted both mitochondrial and lysosomal pathways. One of its mechanisms was the induction of DRP1-mediated mitochondrial fragmentation. Another mechanism was the blocking of late-stage autophagic flux via impairment of lysosomal acidification through V-ATPase inhibition; this blocks the removal of dysfunctional mitochondria and results in reactive oxygen species (ROS) accumulation. Excessive ROS accumulation causes damage to lysosomal membranes and increases lysosomal membrane permeability, which leads to the leakage of cathepsin B. Finally, cathepsin B upregulates Bax-mediated mitochondrial outer membrane permeability and, subsequently, cytosolic cytochrome C-mediated caspase-dependent apoptosis. Thus, the cancer cell killing effect of Tub is enhanced through the formation of a positive feedback loop. The killing effect of Tub on lung cancer cells was verified in xenografted mice. In summary, Tub exerts a dual anticancer effect that involves the disruption of mitochondrial and lysosomal pathways and their interaction and, thereby, has a specific and enhanced killing effect on lung cancer cells.

The Possible Role of Hypothalamus-Pituitary-Adrenal Dysfunction in Epileptic Spasms.

PURPOSE: To analyze diurnal cortisol (COR) rhythms among children with epileptic spasms (ESs) and explore the relationship between endocrine factors, circadian rhythm, and ES. METHODS: This study assessed the COR and adrenocorticotropic hormone (ACTH) levels at 08:00 and 16:00, and COR values at 00:00 among children with ESs. Additionally, the etiology of ESs was analyzed. All cases were divided into the following three etiology groups: genetic group, structural etiology group, and unknown etiology group. ACTH was administered to 24 patients, who were divided into the positive electroclinical outcome group and negative electroclinical outcome group. All data were analyzed using a two-way repeated measures analysis of variance. RESULTS: All children showed a COR rhythm. Controls displayed a significantly different COR rhythm from that in the ES group (Fgroup*COR =24.100, p = 0.000). It was observed that the ACTH levels at 08:00 (t = -3.720) and 16:00 (t=-3.794) and COR levels at 16:00 (t = -2.264) and 00:00 (t = -4.607) in the ES group were significantly higher than those in the control group (p < 0.05); COR levels at 08:00 were significantly lower among individuals in the structural etiology group (F = 3.828, p < 0.05). COR levels at 08:00 in the negative electroclinical outcome group (668.30 ± 227.42) nmol/L were higher than those in the positive electroclinical outcome group (462.25 ± 249.71) nmol/L. CONCLUSION: Our results suggest that the change in COR rhythm is an important pathophysiological characteristic of ESs, suggesting that hypothalamus-pituitary-adrenal axis dysfunction possibly leads to the different manifestations of ESs.