ARHGAP15 promotes metastatic colonization in gastric cancer by suppressing RAC1-ROS pathway.

The molecular mechanism of tumor metastasis, especially how metastatic tumor cells colonize in a distant site, remains poorly understood. Here we reported that ARHGAP15, a Rho GTPase activating protein, enhanced gastric cancer (GC) metastatic colonization, which was quite different from its reported role as a tumor suppressor gene in other cancers. It was upregulated in metastatic lymph nodes and significantly associated with a poor prognosis. Ectopic expression of ARHGAP15 promoted metastatic colonization of gastric cancer cells in murine lungs and lymph nodes in vivo or protected cells from oxidative-related death in vitro. However, genetic downregulation of ARHGAP15 had the opposite effect. Mechanistically, ARHGAP15 inactivated RAC1 and then decreased intracellular accumulation of reactive oxygen species (ROS), thus enhancing the antioxidant capacity of colonizing tumor cells under oxidative stress. This phenotype could be phenocopied by inhibition of RAC1 or rescued by the introduction of constitutively active RAC1 into cells. Taken together, these findings suggested a novel role of ARHGAP15 in promoting gastric cancer metastasis by quenching ROS through inhibiting RAC1 and its potential value for prognosis estimation and targeted therapy.

Major pathological remissions in a patient with stage IIIA nonsmall cell lung cancer after neoadjuvant tislelizumab combined with chemotherapy: a case report and literature review.

INTRODUCTION: Currently, there are few reports of patients with locally advanced lung cancer achieving a clinical complete response by medical treatment. Preoperative neoadjuvant immunotherapy combined with chemotherapy is an option for patients with unresectable, locally advanced nonsmall cell lung cancer (NSCLC) which is of great potential, and may change traditional treatment paradigms. There are relatively few large-scale, high-quality randomized-controlled trials yet, and limitations such as short postoperative follow-up period and immature disease-free survival and overall survival data still persist. Thus, evidence-based medical evidence is urgently needed. It is worthy to explore the further treatment of patients who achieved complete response after initial treatment, though lacking of evidence by now. CASE PRESENTATION: We report a stage IIIA lung squamous cell carcinoma case who achieved a major pathologic remission after neoadjuvant treatment with tislelizumab and chemotherapy. CONCLUSION: Our case study contributes to the existing evidence on the feasibility, efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC.

Randomized Controlled Study of Self-Managed Music-Guided Exercise Intervention Following Intensive Care.

BACKGROUND: Patients who are discharged from the intensive care unit (ICU; termed ICU survivors) often experience persistent physical impairment. OBJECTIVE: The aim of this study was to explore the effects of a self-managed, music-guided exercise intervention on physical outcomes and adherence rates among ICU survivors. METHODS: A randomized controlled design was used. Following ICU discharge, participants admitted to the ICU for at least 5 days were randomly assigned to a music group ( n = 13) or an active control group ( n = 13). Activity counts were measured using an Actiwatch, and the physical health score was measured using the Patient-Reported Outcomes Measurement Information System global health subscale. Adherence to exercise was documented daily. Independent t -tests were used for data analysis. RESULTS: Data were analyzed for 26 participants. The mean age was 62.8 ± 13.8 years, 53.8% were male, 65.4% were White, and mean Acute Physiology and Chronic Health Evaluation severity of illness score was 59 ± 23.4. Global health physical scores were significantly higher in the music group than in the active control group. Although not significantly different, music group participants tended to be more active and had higher physical activity and adherence rates compared to those in the active control group. CONCLUSION: A self-managed, music-guided exercise intervention demonstrated positive benefits on physical outcomes. Future clinical trials with a larger sample size should be conducted to examine the effects of this tailored, cost-effective, innovative, self-managed exercise intervention among ICU survivors.

M2-phenotype tumour-associated macrophages upregulate the expression of prognostic predictors MMP14 and INHBA in pancreatic cancer.

Pancreatic cancer is one of the most lethal gastrointestinal tumours, the most common pathological type is pancreatic adenocarcinoma (PAAD). In recent year, immune imbalanced in tumour microenvironment has been shown to play an important role in the evolution of tumours progression, and the efficacy of immunotherapy has been gradually demonstrated in clinical practice. In this study, we propose to construct an immune-related prognostic risk model based on immune-related genes MMP14 and INHBA expression that can assess the prognosis of pancreatic cancer patients and identify potential therapeutic targets for pancreatic cancer, to provide new ideas for the treatment of pancreatic cancer. We also investigate the correlation between macrophage infiltration and MMP14 and INHBA expression. First, the gene expression data of pancreatic cancer and normal pancreatic tissue were obtained from The Cancer Genome Atlas Program (TCGA) and The Genotype-Tissue Expression public database (GTEx). The differentially expressed immune-related genes between pancreatic cancer samples and normal sample were screened by R software. Secondly, univariate Cox regression analysis were used to evaluate the relationship between immune-related genes and the prognosis of pancreatic cancer patients. A polygenic risk score model was constructed by Cox regression analysis. The prognostic nomogram was constructed, and its performance was evaluated comprehensively by internal calibration curve and C-index. Using the risk model, each patient gets a risk score, and was divided into high- or low- risk groups. The proportion of 22 types of immune cells infiltration in pancreatic cancer samples was inferred by CIBERSOFT algorithm, correlation analysis (Pearson method) was used to analyse the correlation between the immune-related genes and immunes cells. Then, we applied macrophage conditioned medium to culture pancreatic cancer cell line PANC1, detected the expression of MMP14 and INHBA by qRT-PCR and Western blot methods. Knock-down MMP14 and INHBA in PANC1 cells by transfected with shRNA lentiviruses. Detection of migration ability of pancreatic cells was done by trans-well cell migration assay. A subcutaneous xenograft tumour model of human pancreatic cancer in nude mice was constructed. In conclusion, an immune-related gene prognostic model was constructed, patients with high-risk scores have poorer survival status, M2-phenotype tumour-associated macrophages (TAMs) up-regulate two immune-related genes, MMP14 and INHBA, which were used to establish the prognostic model. Knock-down of MMP14 and INHBA inhibited invasion of pancreatic cancer.

Dietary phillygenin supplementation ameliorates aflatoxin B1-induced oxidative stress, inflammation, and apoptosis in chicken liver.

Aflatoxin B1 (AFB1), a mycotoxin contaminating food and feed, can trigger liver immune toxicity and threaten the poultry industry. Phillygenin (PHI) is a natural lignan derived primarily from Forsythia suspensa with hepatoprotective pharmacological and medicinal properties. This research aimed to investigate the preventive effects of PHI on the toxicity of AFB1 in the liver of chickens. Chickens were administered with AFB1 (2.8 mg/kg) and/or treated with PHI (24 mg/kg) for 33 days. The histopathological changes, serum biochemical indices, oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and Nrf2 signaling pathways were measured. Results revealed that dietary PHI ameliorated liver function indicators, reduced the malondialdehyde and inflammatory mediator production and the apoptotic cell number, and increased the antioxidant enzyme contents and Bcl-2 level. The quantitative realtime PCR and Western blot results revealed that PHI reduced p53, cytochrome c, Bax, caspase-9, and caspase-3 levels, normalized the NF-κB p65 phosphorylation, and upregulated the Nrf2 and its downstream genes expression in chicken liver. These results indicated that PHI has beneficial effects on AFB1-induced liver damage, oxidative damage, inflammatory response, apoptosis, and immunotoxicity by inhibiting NF-κB and activating the Nrf2 signaling pathway in chickens. This study provides new insight into the therapeutic uses of PHI.

Tumor-associated macrophages promote the metastasis and growth of non-small-cell lung cancer cells through NF-κB/PP2Ac-positive feedback loop.

Non-small-cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor-associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor-associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage-conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF-κB pathway-dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF-κB pathway signaling. Overexpression of PP2Ac, or the dominant-negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF-κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration.

Ubiquitin carboxyl-terminal hydrolase isozyme L1/UCHL1 suppresses epithelial-mesenchymal transition and is under-expressed in cadmium-transformed human bronchial epithelial cells.

Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, limited knowledge is known about the long-term Cd exposure, especially in the human lung cells. Previously, we showed that chronic Cd-exposed human bronchial epithelial BEAS-2B cells exhibited transformed cell properties, such as anchorage-independent growth, augmented cell migration, and epithelial-mesenchymal transition (EMT). To study these Cd-transformed cells more comprehensively, here, we further characterized their subproteomes. Overall, a total of 63 differentially expressed proteins between Cd-transformed and passage-matched control cells among the five subcellular fractions (cytoplasmic, membrane, nuclear-soluble, chromatin-bound, and cytoskeletal) were identified by mass spectrometric analysis and database searching. Interestingly, we found that the thiol protease ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is one of the severely downregulated proteins in the Cd-transformed cells. Notably, the EMT phenotype of Cd-transformed cells can be suppressed by forced ectopic expression of UCHL1, suggesting UCHL1 as a crucial modulator in the maintenance of the proper differentiation status in lung epithelial cells. Since EMT is considered as a critical step during malignant cell transformation, finding novel cellular targets that can antagonize this transition may lead to more efficient strategies to inhibit cancer development. Our data report for the first time that UCHL1 may play a function in the suppression of EMT in Cd-transformed human lung epithelial cells, indicating that UCHL1 might be a new therapeutic target for chronic Cd-induced carcinogenesis. Graphical abstract.

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

Daytime Activity Is Associated With Discharge to Home in Older Adults Recovering From Critical Illness.

Hospitalized older adults recovering from critical illness after transition of care out of an intensive care unit (ICU) are often inactive, which may affect discharge disposition and hospital length of stay (LOS). The current study explored relationships between early post-ICU activity, discharge disposition, and LOS. Actigraphy measured post-ICU daytime and nighttime activity (mean activity counts/min). Prospective chart review provided discharge disposition and LOS (days). Independent samples t tests compared post-ICU daytime activity by discharge disposition. Multivariate regression examined associations between post-ICU activity and LOS. Post-ICU daytime activity was greater among those discharged home (54.42 [SD = 29.3 counts/min]) than those discharged to a facility (33.26 [SD = 24.26 counts/min]): t(26) = 2.054, p = 0.050). Lower post-ICU daytime activity was associated with longer LOS (ß = -0.322, p = 0.041). Future research should investigate whether post-ICU daytime inactivity during hospitalization is a modifiable risk factor for worse outcomes among older adults discharged from the ICU. [Journal of Gerontological Nursing, 47(2), 13-19.].

Sleep Quality Associated With Motor Function Among Older Adult Survivors of Critical Illness.

BACKGROUND: Poor sleep is associated with worse motor function in older adults. Sleep may affect motor function specifically among older adults recovering from critical illness after transfer out of an intensive care unit (ICU). OBJECTIVES: Describe motor function (grip strength) of older ICU survivors and explore relationships between sleep and ICU-acquired weakness in the early post-ICU transition period. METHODS: We enrolled 30 older adults who were functionally independent prior to hospitalization, mechanically ventilated while in ICU, and within 24-48 hours post-ICU discharge. Handgrip dynamometry assessed post-ICU motor function (fully corrected T score on the National Institutes of Health Motor Battery Grip Strength Test). Actigraphy estimated post-ICU sleep duration (total sleep time [TST]) and fragmentation (wake after sleep onset) over two consecutive nights from 22:00 p.m. to 06:00 a.m.. We identified differences in grip strength by history of obstructive sleep apnea (OSA) using independent-samples t tests. We examined associations between sleep duration and grip strength using exploratory multivariate regression analyses, after adjustment for clinically relevant covariates. RESULTS: Grip strength among this cohort of older ICU survivors was almost 2 SDs below the norm for healthy older adults, indicating considerable ICU-acquired weakness. Grip strength was lower among subjects with history of OSA than those without OSA. Greater TST was associated with worse grip strength, after adjusting for history of OSA and Pittsburgh Sleep Quality Index global score. Moreover, among the subset of male subjects (n = 19), greater TST was significantly and negatively associated with grip strength, after adjusting for Acute Physiology, Age, and Chronic Health Evaluation III score, and Pittsburgh Sleep Quality Index global score. DISCUSSION: Sleep promotion may be a potentially modifiable risk factor to mitigate ICU-acquired weakness in older ICU survivors. We propose that improving sleep throughout recovery from critical illness may indirectly promote better outcomes, as poor grip strength is linked to longer length of hospital stay, higher acuity of discharge disposition, and worsened functional decline in older adults.

Feasibility and acceptability of a self-managed exercise to rhythmic music intervention for ICU survivors.

BACKGROUND: Post-ICU rehabilitation is a challenging clinical issue for patients discharged from an Intensive Care Unit ("ICU survivors"). Our exercise to rhythmic music intervention was designed to allow ICU survivors to self-manage their exercise by following a personalized, recorded exercise playlist. AIM: Our study reports the feasibility and acceptability of an innovative music intervention among ICU survivors enrolled in a randomized controlled pilot study. METHODS: ICU survivors, admitted in ICU for at least 5 days and cognitively intact, were randomly assigned to an exercise to rhythmic music group (n = 10) or an active control group (n = 10). Participants in the music group were taught to self-manage exercise by listening to a recorded playlist of instructions and music-facilitated movements tailored to their musical preference and exercise ability. Participants in the control group were provided a brochure with exercise instructions. After 5 days or at hospital discharge, participants completed an 8-item acceptability questionnaire and were interviewed. Content analysis was conducted. RESULTS: 18 Participants were included for final analysis. Participants were 61.8 ± 14.7 years old, predominantly male (66.7%), and Caucasian (55.6%). Results demonstrated feasibility, as the study team was able to meet the enrollment goal of 5-6 participants per month. Three themes related to general, physical, and psychosocial benefits were identified. Based on positive feedback, the exercise to rhythmic music intervention was deemed acceptable. CONCLUSION: The exercise to rhythmic music intervention was feasible and acceptable, suggesting that clinical trials with larger sample sizes should investigate the effects of the intervention on outcomes among ICU survivors.

An analysis of the mechanism underlying photocatalytic disinfection based on integrated metabolic networks and transcriptional data.

Photocatalytic disinfection has long been used to combat pathogenic bacteria. However, the specific mechanism underlying photocatalytic disinfection and its corresponding targets remain unclear. In this study, an analysis of the potential mechanism underlying photocatalytic disinfection was performed based on integrated metabolic networks and transcriptional data. Two sets of RNA-seq data (wild type and a photocatalysis-resistant mutant mediated by titanium dioxide (TiO2)) were processed to constrain the genome scale metabolic models (GSMM) of E. coli. By analyzing the metabolic network, the differential metabolic flux of every reaction was computed in constrained GSMM, and several significantly differential metabolic fluxes in reactions were extracted and analyzed. Most of these reactions were involved in the transmembrane transport of substances and occurred on the inner membrane or were an important component of the cell membrane. These results, which are consistent with the reported information, validated our analysis process. In addition, our work also identified other new and valuable metabolic pathways, such as the reaction ALCD2x, which has a great effect on the energy production process under bacterial anaerobic conditions. The DHAK reaction is also related to the metabolic process of ATP. These reactions with large differential metabolic fluxes merit further research. Additionally, to provide a strategy to address photocatalysis-resistant mutant bacteria, a metabolic compensation analysis was also performed. The metabolic compensation analysis results provided suggestions for a combined method that can effectively combat resistant bacteria. This method could also be used to explore the mechanisms of drug resistance in other microorganisms.

ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2.

The oncogenic roles of ETV4 have been revealed in multiple cancers. However, its expression and functions in lung cancer are rarely explored. Here, we firstly detected the expression of ETV4 in lung adenocarcinoma (LUAD) via online data and local experiment validation. Furthermore, we explored the functions and corresponding mechanisms of ETV4 in LUAD. Upregulation of ETV4 in LUAD is indicated by online data and our results of qPCR, Western blot and immunohistochemistry in collective tissue samples. ETV4 knockdown significantly inhibits proliferation and invasion in LUAD indicated by the outcomes of CCK8, plate clone formation, and Transwell invasion assays. Mechanistically, chromatin immunoprecipitation and luciferase reporter system assays indicated that ETV4 could directly bind at the promoter of MSI2 and promote its transcription. Furthermore, ectopic expression MSI2 can rescue the inhibitory effects caused by ETV4 knockdown in LUAD. Therefore, we proved that upregulation of ETV4 could promote proliferation and invasion of LUAD by transcriptionally upregulating MSI2 offering a potential therapy treatment target of LUAD.

Acute and chronic cadmium telluride quantum dots-exposed human bronchial epithelial cells: The effects of particle sizes on their cytotoxicity and carcinogenicity.

Quantum dots (QDs) are semiconducting nanocrystals with unique optical properties. When coated with shell/capping, QDs are not deleterious to cells and organisms. However, when QDs are retained in the cellular environment for a certain period of time, their coatings may be degraded, yielding "naked" QDs. Although some studies have documented the acute effects of cadmium telluride (CdTe) QDs in various cell lines, however, to our knowledge, there are no published studies on the chronic effects of CdTe QDs in normal lung cells. In this study, we therefore sought to study the effects of CdTe QDs of various particle sizes on their cytotoxicity and carcinogenicity in normal human bronchial epithelial cells (BEAS-2B). A total of three particle sizes of CdTe QD with emission maximum at 520, 580, and 730 nm were employed (abbreviated as 520Q, 580Q, and 730Q, respectively). Our results indicated that acute exposure to 520Q (∼2.04 nm in diameter) and 580Q (∼3.24 nm in diameter) elicited dose-dependent cytotoxicity; while acute exposure to 730Q (∼5.40 nm in diameter) elicited negligible cytotoxicity in BEAS-2B cells. Notably, chronic exposure to CdTe QD of all three tested particle sizes induced BEAS-2B cell transformation as evidenced by enhanced cell migration and anchorage-independent growth on soft agar. Taken together, our findings suggest that CdTe QDs are potent human lung carcinogens.

Epiproteome profiling of cadmium-transformed human bronchial epithelial cells by quantitative histone post-translational modification-enzyme-linked immunosorbent assay.

Cadmium (Cd), a carcinogenic toxic metal, is pervasively distributed in the soil, water and air. Chronic exposure to Cd has been correlated to lung disease development including cancers. Although many studies have been conducted to investigate the proteome response of cells challenged with Cd, the epiproteomic responses (i.e., global histone post-translational modifications [PTMs]), particularly in human lung cells, are largely unexplored. Here, we provide an epiproteome profiling of human bronchial epithelial cells (BEAS-2B) chronically treated with cadmium chloride (CdCl2 ), with the aim of identifying global epiproteomic signatures in response to Cd epigenotoxicity. Total histone proteins from Cd-treated and untreated BEAS-2B cells were isolated and subject to quantitative histone PTM-enzyme-linked immunosorbent assay using 18 histone PTM antibodies. Our results unveiled that chronic Cd treatment led to the marked downregulation of H3K4me2 and H3K36me3 and upregulation of H3K9acS10ph, H4K5ac, H4K8ac and H4K12ac PTM marks. Cd-treated cells exhibit transformed cell properties as evidenced by enhanced cell migration and the ability of anchorage-independent growth on soft agar. Notably, treatment of Cd-transformed cells with C646, a potent histone acetyltransferase inhibitor, suppressed the expression of mesenchymal marker genes and cell migration ability of these cells. Taken together, our studies provide for the first time the global epiproteomic interrogation of chronic Cd-exposed human lung cells. The identified aberrant histone PTM alterations associated with Cd-induced epigenotoxicity likely account for the epithelial-mesenchymal transition and neoplastic survival of these cells.

Optimal frequency of tooth brushing in mechanically ventilated adults: Study protocol for a randomized controlled trial.

The optimal frequency of tooth brushing in the critically ill has not been experimentally determined. For mechanically ventilated patients, optimal frequency of tooth brushing is an important unresolved issue as there is little evidence to judge the benefits or associated risks of tooth brushing. Given this knowledge gap, the project's overall goal is to determine the optimal frequency of tooth brushing (once, twice, or three times daily) for mechanically ventilated adults. A prospective, randomized, experimental design is used. Specifically, 345 subjects, with 207 expected to complete the study, are randomly assigned within 36 hr of intubation to one of three groups (once, twice, or three times tooth brushing daily). Tooth brushing with a soft compact-head toothbrush takes approximately 2 min. Dental plaque assessment, gingival crevicular fluid (GCF) determination for IL-1ß, and data regarding healthcare-acquired infection (HAI) and clinical status are collected at baseline and daily in-hospital. The clinical impact of daily frequency of tooth brushing in relation to extent of dental plaque and inflammation reflected by GCF analysis will be compared by the three treatment arms. In addition, evaluation of safety for HAIs will be compared based on calculation of the number needed to harm. The trial will empirically determine the optimal frequency of tooth brushing in mechanically ventilated adults, balancing benefits and risks. This contribution is significant because it will have immediate impact on bedside nursing practice, and is a final component necessary for specific evidence-based guidelines for the common nursing intervention of oral care in mechanically ventilated adults.

[Influence of cow's milk protein allergy on the diagnosis of functional gastrointestinal diseases based on the Rome IV standard in infants and young children].

OBJECTIVE: To study the influence of cow's milk protein allergy (CMPA) on the diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV standard in infants and young children. METHODS: A total of 84 children aged 1 month to 3 years who were diagnosed with CMPA were enrolled as the case group, and 84 infants and young children who underwent physical examination and had no CMPA were enrolled as the control group. The pediatricians specializing in gastroenterology asked parents using a questionnaire for the diagnosis of FGID based on the Rome IV standard to assess clinical symptoms and to diagnose FGID. RESULTS: The case group had a significantly higher incidence rate of a family history of allergies than the control group (P<0.05). In the case group, 38 (45%) met the Rome IV standard for the diagnosis of FGID, while in the control group, 13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID, the case group had significantly higher diagnostic rates of reflex, functional diarrhea, difficult defecation, and functional constipation than the control group (P<0.05). The children who were diagnosed with FIGD in the control group were given conventional treatment, and those in the case group were asked to avoid the intake of cow's milk protein in addition to the conventional treatment. After 3 months of treatment, the case group had a significantly higher response rate to the treatment than the control group (P<0.05). CONCLUSIONS: In infants and young children, CMPA has great influence on the diagnosis of FGID based on the Rome IV standard. The possibility of CMPA should be considered during the diagnosis of FGID.

Changes in Sleep With Auricular Point Acupressure for Chronic Low Back Pain.

The purpose of this study was to report sleep quality from 4 weeks of auricular point acupressure that was designed for chronic low back pain and determine the relationship between pain intensity and sleep quality. Participants were randomized into the APA group (n = 30) or the sham-APA group (n = 31). At baseline assessment, 87% of the participants reported poor sleep quality. Participants who received APA had decreased daytime disturbance and improved global Pittsburgh Sleep Quality Index scores at end of intervention (EOI) and 1-month follow up compared to participants in the sham-APA group. For the APA group, both the sleep duration and wake after sleep onset decreased gradually during the 4-week APA (0.56% and 0.23% daily change, respectively).

Day-to-Day Changes of Auricular Point Acupressure to Manage Chronic Low Back Pain: A 29-day Randomized Controlled Study.

OBJECTIVE: The purpose of this study was to determine the effects of a 4-week auricular point acupressure (APA) treatment on chronic low back pain (CLBP) outcomes and examine the day-to-day variability of CLBP in individuals receiving APA for CLBP over 29 days. DESIGN: This was a prospective, randomized controlled trial (RCT). Data were collected at baseline, during each of the four office visits for APA treatment, after the completion of the 4-week intervention, and 1 month after the last treatment. A daily diary was given to each participant to record his or her APA practices, analgesic use, and pain intensity. INTERVENTIONS: APA was used to manage CLBP. The participants received one APA treatment per week for 4 weeks. PATIENTS AND SETTING: Sixty-one participants with CLBP were randomized into either a real APA or sham APA treatment group. Participants were recruited from primary care offices and clinics or through the Research Participant Registry at the University of Pittsburgh. RESULTS: Among participants in the real APA group, a 30% reduction of worst pain was exhibited after the first day of APA treatment, and continuous reduction in pain (44%) was reported by the completion of the 4-week APA. This magnitude of pain reduction reached the clinically significant level of improvement reported in other clinical trials of chronic pain therapies. Analgesic use by participants in the real APA group also was reduced compared with use by participants in the sham group. CONCLUSION: This study shows that APA is a promising pain management strategy that is not invasive and can be self-managed by participants for CLBP. Given the day-to-day fluctuation in ratings, the tighter ecologic assessment of pain scores and other treatment parameters are an important pragmatic aspect of the design of chronic pain studies.

Clinical Analysis of Patients with Primary Blepharospasm: A Report of 100 Cases in China.

PURPOSE: This study explored the clinical characteristics, diagnosis and treatments of primary blepharospasm. METHODS: In this retrospective analysis, 100 patients with blepharospasm were enrolled. Data were collected from medical records and face-to-face interviews with patients and their families. RESULTS: The age of onset was 56.4 ± 2.7 (range, 32-76 years). The duration between onset and accurate diagnosis was 38.7 ± 36.0 months (range, 2-120 months). Dry eyes occurred in 54% of the patients. The initial diagnostic accuracy was 10%. Dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis caused the most confusion in the differential diagnosis. Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in all patients. CONCLUSIONS: Regular botulinum toxin type A injections improved both eyelid spasms and subjective ocular symptoms in blepharospasm patients. The differentiation of primary blepharospasm differentiation from dry eye syndrome, conjunctivitis/keratitis and myasthenia gravis must be improved.