Low-Dose Naltrexone for Excoriation Disorder.

Excoriation (skin-picking) disorder (ED) is a condition characterized by the repeated compulsion to pick at the skin, causing physical trauma and psychiatric distress. Patients often desire to cease skin-picking behavior but are unable to do so. Multiple treatment modalities are effective for ED, including naltrexone. Previous reports of naltrexone for ED were at a high dose of 50 mg. The efficacy of low-dose naltrexone (LDN) at 4.5 mg in managing ED has not been reported. We present a case of a 51-year-old female with ED who was evaluated in the pain clinic for fibromyalgia management. Her medications included gabapentin 600 mg PO TID and a history of opioid prescription for diffuse pain. She was started on naltrexone 4.5 mg PO QD for the management of fibromyalgia. Three months later, the patient reported improvement in her skin-picking disorder, with a lessened compulsion to itch at her skin and improved healing of existing lesions. When the naltrexone was temporarily interrupted for an elective procedure, her lesions worsened. Her lesions improved after she resumed the medication. Thereby, this patient experienced a therapeutic benefit from naltrexone for her skin-picking disorder, as demonstrated by the temporal changes in her symptoms. To our knowledge, this is the first reported case of ED improving with LDN, as other cases utilized 50 mg. Though few clinical trials or systematic reviews recommend the use of naltrexone for EDs, our case supports trialing LDN in the appropriate context.

Integrated chemical characterization, metabolite profiling, and pharmacokinetics analysis of Zhijun Tangshen Decoction by UPLC-Q/TOF-MS.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide and a major public issue affecting the health of people. Therefore, it is essential to explore effective drugs for the treatment of DN. In this study, the traditional Chinese medicine (TCM) formula, Zhijun Tangshen Decoction (ZJTSD), a prescription modified from the classical formula Didang Decoction, has been used in the clinical treatment of DN. However, the chemical basis underlying the therapeutic effects of ZJTSD in treating DN remains unknown. In this study, compounds of ZJTSD and serum after oral administration in rats were identified and analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Meanwhile, a semi-quantitative approach was used to analyze the dynamic changes in the compounds of ZJTSD in vivo. UPLC-Q/TOF-MS analysis identified 190 compounds from ZJTSD, including flavonoids, anthraquinones, terpenoids, phenylpropanoids, alkaloids, and other categories. A total of 156 xenobiotics and metabolites, i.e., 51 prototype compounds and 105 metabolites, were identified from the compounds absorbed into the blood of rats treated with ZJTSD. The results further showed that 23 substances with high relative content, long retention time, and favorable pharmacokinetic characteristics in vivo deserved further investigations and validations of bioactivities. In conclusion, this study revealed the chemical basis underlying the complexity of ZJTSD and investigated the metabolite profiling and pharmacokinetics of ZJTSD-related xenobiotics in rats, thus providing a foundation for further investigation into the pharmacodynamic substance basis and metabolic regulations of ZJTSD.

Preparation and Characterization of Soluble Dietary Fiber Edible Packaging Films Reinforced by Nanocellulose from Navel Orange Peel Pomace.

The packaging problem with petroleum-based synthetic polymers prompts the development of edible packaging films. The high value-added reuse of navel orange peel pomace, which is rich in bioactive compounds, merited more considerations. Herein, nanocellulose (ONCC) and soluble dietary fiber (OSDF) from navel orange peel pomace are firstly used to prepare dietary fiber-based edible packaging films using a simple physical blend method, and the impact of ONCC on the film's properties is analyzed. Adopting three methods in a step-by-step approach to find the best formula for edible packaging films. The results show that dietary-fiber-based edible packaging films with 4 wt.% ONCC form a network structure, and their crystallinity, maximum pyrolysis temperature, and melting temperature are improved. What's more, dietary-fiber-based edible packaging films have a wide range of potential uses in edible packaging.

Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

Development, assessment and validation of a novel prediction nomogram model for risk identification of tracheobronchial tuberculosis in patients with pulmonary tuberculosis.

OBJECTIVE: Tracheobronchial tuberculosis (TBTB), a specific subtype of pulmonary tuberculosis (PTB), can lead to bronchial stenosis or bronchial occlusion if not identified early. However, there is currently no available means for predicting the risk of associated TBTB in PTB patients. The objective of this study was to establish a risk prediction nomogram model for estimating the associated TBTB risk in every PTB patient. METHODS: A retrospective cohort study was conducted with 2153 PTB patients. Optimised characteristics were selected using least absolute shrinkage and selection operator regression. Multivariate logistic regression was applied to build a predictive nomogram model. Discrimination, calibration and clinical usefulness of the prediction model were assessed using C-statistics, receiver operator characteristic curves, calibration plots and decision analysis. The developed model was validated both internally and externally. RESULTS: Among all PTB patients who underwent bronchoscopies (n=2153), 40.36% (n=869) were diagnosed with TBTB. A nomogram model incorporating 11 predictors was developed and displayed good discrimination with a C-statistics of 0.782, a sensitivity of 0.661 and a specificity of 0.762 and good calibration with a calibration-in-the-large of 0.052 and a calibration slope of 0.957. Model's discrimination was favourable in both internal (C-statistics, 0.782) and external (C-statistics, 0.806) validation. External validation showed satisfactory accuracy (sensitivity, 0.690; specificity, 0.804) in independent cohort. Decision curve analysis showed that the model was clinically useful when intervention was decided on at the exacerbation possibility threshold of 2.3%-99.2%. A clinical impact curve demonstrated that our model predicted high-risk estimates and true positives. CONCLUSION: We developed a novel and convenient risk prediction nomogram model that enhances the risk assessment of associated TBTB in PTB patients. This nomogram can help identify high-risk PTB patients who may benefit from early bronchoscopy and aggressive treatment to prevent disease progression.

Establishment and bioinformatics evaluation of the ethanol combined with palmitic acid-induced mouse hepatocyte AFLD model (the Hu-Qiu Model).

Chronic alcoholic liver disease has brought great harm to human health. Alcoholic fatty liver disease is the first stage in the progression of all chronic alcoholic liver diseases. At present, there is no cell model that fully matches the etiology (high-fat diet + alcohol) of human alcoholic fatty liver disease. We used 100 mM ethanol +6.25 µM PA to establish the ethanol combined with PA-induced mouse hepatocyte AFLD model (EP-AFLD hepatocyte model) and performed the RNA-seq transcriptome sequencing. Through bioinformatics analysis and comparison, we discovered that the EP-AFLD hepatocyte model was more suitable for studying the pathological mechanism of AFLD than the mouse AFLD hepatocyte model induced by ethanol alone. And through bioinformatics analysis, we further discovered that 77 genes from the differential expression gene set of EP-AFLD hepatocyte model were engaged in the pathological process of mouse AFLD and 40 genes were involved in the pathogenesis of both mouse AFLD and human AFLD. In this study, a novel mouse hepatocyte AFLD model was successfully established by combining ethanol and PA, which can be used to study the molecular mechanism of the pathogenesis of AFLD in mice or humans. This study will provide a brand-new in vitro experimental platform for the in-depth study of AFLD pathogenesis and the screening of AFLD therapeutic drugs.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Clinical, Microbiological, and Molecular Characterization of Candia (Starmera) stellimalicola, a Rare Fungal Pathogen Causing Human Infections.

Candia (Starmera) stellimalicola is a yeast species spread worldwide and recovered from varieties of ecological reservoirs, but human infections are rarely reported. In this study, we reported an intra-abdominal infection case caused by C. stellimalicola and described its microbiological and molecular characteristics. C. stellimalicola strains were isolated from ascites fluid of an 82-year-old male patient having diffuse peritonitis with fever and elevated WBC counts. Routine biochemical and MALDI-TOF MS methods failed to identify the pathogenic strains. Phylogenetic analysis of 18S, 26S and internal transcribed space (ITS) rDNA regions, as well as whole-genome sequence identified the strains as C. stellimalicola. Compared with other Starmera species, C. stellimalicola had unique physiological characteristics including thermal tolerance (able to grow at 42 °C), which may prompt its environmental adaptability and potential for opportunistic human infection. Fluconazole minimum inhibitory concentration (MIC) values of the strains identified in this case was 2 mg/L, and the patient had a favorable outcome after receiving fluconazole treatment. In comparison, the majority of C. stellimalicola strains previously documented had high MIC values (≥ 16 mg/L) to fluconazole. In conclusion, with the raise in human infections caused by rare fungal pathogens, molecular diagnostic remains the most efficient way for accurate species identification; and antifungal susceptibility testing is essential to guide proper patient management.

Characteristics analysis of 157 cases of central airway stenosis due to tracheobronchial tuberculosis: A descriptive study.

Background: Tracheobronchial stenosis, particularly central airway stenosis, which frequently results in severe complications such as lung damage, occurs in patients with tracheobronchial tuberculosis (TBTB). Objectives: To analyze the clinical characteristics of patients with central airway stenosis due to tuberculosis (CASTB). Methods: Retrospective analysis was performed on the clinical features, radiological features, bronchoscopic features and treatment of 157 patients who were diagnosed with CASTB in two tertiary hospitals in Chongqing, China, from May 2020 to May 2022. Results: CASTB mostly occurs in young patients and females. Patients with CASTB exhibited different symptoms repeatedly during the disease, especially varying degrees of dyspnea, prompting many patients to undergo bronchoscopic intervention and even surgery. Patients with cicatricial strictures constituted the highest proportion of the TBTB subtype with CASTB and 35.7% of the patients with CASTB were found to have tracheobronchomalacia (TBM) under bronchoscopy. CASTB and TBM mainly involved the left main bronchus. Patients with lower levels of education had higher rates of TBM. Patients with TBM manifested shortness of breath more frequently than patients without TBM. Patients with TBTB who had undergone bronchoscopic interventions have a higher rate of TBM. Conclusions: Despite mostly adequate anti-tuberculosis chemotherapy, patients with TBTB can present with CASTB involving severe scarring stenosis, bronchial occlusion, tracheobronchomalacia and even destroyed lung.

Association of CYP24A1 with survival and drug resistance in clinical cancer patients: a meta-analysis.

BACKGROUND: Acquired chemo-drug resistance constantly led to the failure of chemotherapy for malignant cancers, consequently causing cancer relapse. Hence, identifying the biomarker of drug resistance is vital to improve the treatment efficacy in cancer. The clinical prognostic value of CYP24A1 remains inconclusive, hence we aim to evaluate the association between CYP24A1 and the drug resistance in cancer patients through a meta-analysis approach. METHOD: Relevant studies detecting the expression or SNP of CYP24A1 in cancer patients up till May 2022 were systematically searched in four common scientific databases including PubMed, EMBASE, Cochrane library and ISI Web of Science. The pooled hazard ratios (HRs) indicating the ratio of hazard rate of survival time between CYP24A1high population vs CYP24A1low population were calculated. The pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were used to explore the association between CYP24A1's expression or SNP with survival, metastasis, recurrence, and drug resistance in cancer patients. RESULT: Fifteen studies were included in the meta-analysis after an initial screening according to the inclusion and exclusion criteria. There was a total of 3784 patients pooled from all the included studies. Results indicated that higher expression or SNP of CYP24A1 was significantly correlated with shorter survival time with pooled HRs (95% CI) of 1.21 (1.12, 1.31), metastasis with pooled ORs (95% CI) of 1.81 (1.11, 2.96), recurrence with pooled ORs (95% CI) of 2.14 (1.45, 3.18) and drug resistance with pooled HRs (95% CI) of 1.42 (1.17, 1.68). In the subgroup analysis, cancer type, treatment, ethnicity, and detection approach for CYP24A1 did not affect the significance of the association between CYP24A1 expression and poor prognosis. CONCLUSION: Findings from our meta-analysis demonstrated that CYP24A1's expression or SNP was correlated with cancer progression and drug resistance. Therefore, CYP24A1 could be a potential molecular marker for cancer resistance.

YTH Domain Proteins Play an Essential Role in Rice Growth and Stress Response.

As the most prevalent epi-transcriptional modification, m6A modifications play essential roles in regulating RNA fate. The molecular functions of YTH521-B homology (YTH) domain proteins, the most known READER proteins of m6A modifications, have been well-studied in animals. Although plants contain more YTH domain proteins than other eukaryotes, little is known about their biological importance. In dicot species Arabidopsis thaliana, the YTHDFA clade members ECT2/3/4 and CPSF30-L are well-studied and important for cell proliferation, plant organogenesis, and nitrate transport. More emphasis is needed on the biological functions of plant YTH proteins, especially monocot YTHs. Here we presented a detailed phylogenetic relationship of eukaryotic YTH proteins and clustered plant YTHDFC clade into three subclades. To determine the importance of monocot YTH proteins, YTH knockout mutants and RNAi-induced knockdown plants were constructed and used for phenotyping, transcriptomic analysis, and stress treatments. Knocking out or knocking down OsYTHs led to the downregulation of multicellular organismal regulation genes and resulted in growth defects. In addition, loss-of-function ythdfa mutants led to better salinity tolerance whereas ythdfc mutants were more sensitive to abiotic stress. Overall, our study establishes the functional relevance of rice YTH genes in plant growth regulation and stress response.

Collective outbreak of severe acute histoplasmosis in immunocompetent Chinese in South America: the clinical characteristics and continuous monitoring of serum cytokines/chemokines.

BACKGROUND: Acute histoplasmosis is a rare fungal disease in China. This study is aimed to summarize the clinical characteristics of the first large-scale outbreak of imported acute histoplasmosis in Chinese, so as to provide suggestions for clinical diagnosis and treatment. METHODS: We collected the symptoms, signs, laboratory examination and imaging data of 10 patients in so far the biggest outbreak of imported acute histoplasmosis in immunocompetent Chinese. Their clinical characteristics and time-varying cytokine/chemokine levels were analyzed, and rank correlation analysis between these markers was utilized to show their condition. RESULTS: The 10 patients of imported acute histoplasmosis were working without any respiratory protection in an abandoned mine tunnel in Guyana. The most common symptoms were fever and cough. Their chest CT imaging showed multiple nodular shadows in lungs. Laboratory examination showed that at admission the CRP, PCT, LDH, CysC, G-test, ß2-MG were all increased in at least 9 patients, and the CD4/CD8 was decreased to < 1 in all patients. Most cytokines/chemokines (other than IL-4, IL-12, INF-α, TNF-α) varied widely with patients and time, but their overall trend is higher at admission and decreasing gradually during hospitalization, especially for the IL-6, IL-8, IL-10 and IFN-γ. The LDH, CysC, G-test, ß2-MG, N/L, IL-6, IL-8, IL-10, IFN-γ, IL-27 are in positive associations to both CRP and PCT. CONCLUSIONS: The diagnosis of acute histoplasmosis needs a comprehensive analysis of epidemiological history, clinical symptoms and signs, and results of imaging, laboratory, microbiological and pathological examinations. Although none of the CRP, PCT, G-test, N/L, LDH, CysC, ß2-MG, IL-6, IL-8, IL-10, IFN-γ shows specificity in the diagnosis of acute histoplasmosis, there is possibility that the above factors might help in the inflammation and prognosis estimation. However, more studies and further investigation are still required for the verification.

Epiregulin increases stemness-associated genes expression and promotes chemoresistance of non-small cell lung cancer via ERK signaling.

BACKGROUND: Chemoresistance often causes the failure of treatment and death of patients with advanced non-small-cell lung cancer. However, there is still no resistance genes signature and available enriched signaling derived from a comprehensive RNA-Seq data analysis of lung cancer patients that could act as a therapeutic target to re-sensitize the acquired resistant cancer cells to chemo-drugs. Hence, in this study, we aimed to identify the resistance signature for clinical lung cancer patients and explore the regulatory mechanism. METHOD: Analysis of RNA-Seq data from clinical lung cancer patients was conducted in R studio to identify the resistance signature. The resistance signature was validated by survival time of lung cancer patients and qPCR in chemo-resistant cells. Cytokine application, small-interfering RNA and pharmacological inhibition approaches were applied to characterize the function and molecular mechanism of EREG and downstream signaling in chemoresistance regulation via stemness. RESULTS: The RTK and vitamin D signaling were enriched among resistance genes, where 6 genes were validated as resistance signature and associated with poor survival in patients. EREG/ERK signaling was activated by chemo-drugs in NSCLC cells. EREG protein promoted the NSCLC resistance to chemo-drugs by increasing stemness genes expression. Additionally, inhibition of EREG/ErbB had downregulated ERK signaling, resulting in decreased expression of stemness-associated genes and subsequently re-sensitized the resistant NSCLC cells and spheres to chemo-drugs. CONCLUSIONS: These findings revealed 6 resistance genes signature and proved that EREG/ErbB regulated the stemness to maintain chemoresistance of NSCLC via ERK signaling. Therefore, targeting EREG/ErbB might significantly and effectively resolve the chemoresistance issue.

Two new supramolecular Ag(I) coordination polymers: luminescent properties and treatment activity on glioblastoma.

Two new Ag(I) coordination polymers, namely [Ag(bpp)]·0.5 n(1,5-NDSA)·n(H2O) (1) and [Ag2(bpp)2]n·n(2,7-NDSA)·2 n(H2O)·n(CH3CN) (2) (Na2(1,5-NDSA) = sodium 1,5-naphthalenedisulfonate dibasic, Na2(2,7-NDSA) = sodium 1,5-naphthalenedisulfonate dibasic, bpp is 1,3-bis(4-pyridyl)propane), were generated via the solution evaporation method under room temperature. Moreover, the solids of these two compounds display strong luminescence emission at RT. And the application values of the compounds against the glioblastoma treatment were determined, and the corresponding mechanism was simultaneously tested. The analysis of CCK-8 was first implemented and the glioblastoma viability was measured. The real-time RT-PCR was next performed, and the signaling pathway activation of VEGF in glioblastoma cells was tested after treating by the above compound.

Epidemiology of concurrent extrapulmonary tuberculosis in inpatients with extrapulmonary tuberculosis lesions in China: a large-scale observational multi-centre investigation.

AIMS: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. METHODS: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. RESULTS: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). CONCLUSIONS: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.