USP18 promotes colon adenocarcinoma progression via targeting the ERK-MNK signaling pathway.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide and is one of the leading causes of cancer-related mortality. Ubiquitin-specific peptidase 18 (USP18) protein has been reported to exert different tumor-related effects in distinct tumor types. Here, we initially investigated the expression and signaling pathways of USP18 in colon adenocarcinoma (COAD). METHODS: A quantitative real-time PCR was conducted to evaluate the mRNA level of USP18 in cultured cells. Immunohistochemical staining was used to explore the protein expression of USP18 in clinical COAD samples. Specific knockdown was achieved by transient transfection of small interfering RNAs into SW480 and HT29 cells using Lipo3000. Cell conting kit-8 assay, transwell assay and matrigel-transwell assays were conducted to evaluate proliferation, migration and invasion capacities, respectively. Western blotting was performed to analyze downstream signaling pathways. A chi-squared test and univariate and multivariate analyses were used to evaluate the clinical data. Xenografts from mice model were assessed to validate the in vitro findings. RESULTS: Higher USP18 level was identified in COAD tissues and was positively correlated with advanced tumor stage. High USP18 protein expression indicated poorer prognosis of COAD patients. Silencing USP18 suppressed COAD cell proliferation and invasion via destabilizing extracellular signal-regulated kinase (ERK) protein and suppressing ERK downstream pathways. Simultaneously silencing interferon-stimulated gene 15 (ISG15) with USP18 can partially rescue the tumor cell viability, indicating its involvement in USP18 signaling. The oncogenic effects of USP18 were also confirmed in mice models. CONCLUSIONS: USP18 plays oncogenic effects in colon adenocarcinoma via ISG15-ERK pathways. High USP18 expression indicates poor clinical outcomes for colon adenocarcinoma patients.

Gynostemma pentaphyllum Extract Alleviates NASH in Mice: Exploration of Inflammation and Gut Microbiota.

NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.

Risk analysis for subsequent fracture of osteoporotic fractures in Chinese women over age 60: a nationwide cross-sectional study.

Prevention of subsequent fracture is a major public health challenge in the field of osteoporosis prevention and treatment, and older women are at high risk for osteoporotic fractures. This study aimed to examine factors associated with subsequent fracture in older Chinese women with osteoporosis. We collected data on 9212 older female patients with osteoporotic fractures from 580 medical institutions in 31 provinces of China. Higher odds of subsequent fractures were associated with age of 70-79 years (OR 1.218, 95% CI 1.049-1.414), age ≥ 80 (OR 1.455, 95% CI 1.222-1.732), index fracture site was vertebrae (OR 1.472, 95% CI 1.194-1.815) and hip (OR 1.286, 95% CI 1.041-1.590), index fracture caused by fall (OR 1.822, 95% CI 1.281-2.591), strain (OR 1.587, 95% CI 1.178-2.139), no inducement (OR 1.541, 95% CI 1.043-2.277), and assessed as high risk of fracture (OR 1.865, 95% CI 1.439-2.416), BMD T-score ≤ -2.5 (OR 1.725, 95% CI 1.440-2.067), history of surgery (OR 3.941, 95% CI 3.475-4.471) and trauma (OR 8.075, 95% CI 6.941-9.395). Low risk of fall (OR 0.681, 95% CI 0.513-0.904), use of anti-osteoporosis medication (AOM, OR 0.801, 95% CI 0.693-0.926), and women who had received fall prevention health education (OR 0.583, 95% CI 0.465-0.730) associated with lower risk. The areas under the curve of the prediction model was 0.818. The sensitivity was 67.0% and the specificity was 82.0%. The prediction model showed a good ability to predict the risk of subsequent fracture in older women with osteoporotic fractures and are suitable for early self-measurement which may benefit post-fracture management.

GSEA analysis identifies potential drug targets and their interaction networks in coronary microcirculation disorders.

Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.

Highly Crystalline Copper Aluminum-Layered Double Hydroxides with Intrinsic Fenton-Like Catalytic Activity for Robust Oral Health Management.

As the main challenge of dental healthcare, oral infectious diseases are highly associated with the colonization of pathogenic microbes. However, current antibacterial treatments in the field of stomatology still lack a facile, safe, and universal approach. Herein, we report the controllable synthesis of copper aluminum-layered double hydroxides (CuAl-LDHs) with high Fenton-like catalytic activity, which can be utilized in the treatment of oral infectious diseases with negligible side effects. Our strategy can efficiently avoid the unwanted doping of other divalent metal ions in the synthesis of Cu-contained LDHs and result in the formation of binary CuAl-LDHs with high crystallinity and purity. Evidenced by experimental and theoretical results, CuAl-LDHs exhibit excellent catalytic ability toward the ·OH generation in the presence of H2O2 and hold strong affinity toward bacteria, endowing them with great catalytic sterilization against both Gram-positive and Gram-negative bacteria. As expected, these CuAl-LDHs provide outstanding treatments for mucosal infection and periodontitis by promoting wound healing and remodeling of the periodontal microenvironment. Moreover, toxicity investigation demonstrates the overall safety. Accordingly, the current study not only provides a convenient and economic strategy for treating oral infectious diseases but also extends the development of novel LDH-based Fenton or Fenton-like antibacterial reagents for further biomedical applications.

Development and validation of a novel colonoscopy withdrawal time indicator based on YOLOv5.

BACKGROUND AND AIM: The study aims to introduce a novel indicator, effective withdrawal time (WTS), which measures the time spent actively searching for suspicious lesions during colonoscopy and to compare WTS and the conventional withdrawal time (WT). METHODS: Colonoscopy video data from 472 patients across two hospitals were retrospectively analyzed. WTS was computed through a combination of artificial intelligence (AI) and manual verification. The results obtained through WTS were compared with those generated by the AI system. Patients were categorized into four groups based on the presence of polyps and whether resections or biopsies were performed. Bland Altman plots were utilized to compare AI-computed WTS with manually verified WTS. Scatterplots were used to illustrate WTS within the four groups, among different hospitals, and across various physicians. A parallel box plot was employed to depict the proportions of WTS relative to WT within each of the four groups. RESULTS: The study included 472 patients, with a median age of 55 years, and 57.8% were male. A significant correlation with manually verified WTS (r = 0.918) was observed in AI-computed WTS. Significant differences in WTS/WT among the four groups were revealed by the parallel box plot (P < 0.001). The group with no detected polyps had the highest WTS/WT, with a median of 0.69 (interquartile range: 0.40, 0.97). WTS patterns were found to be varied between the two hospitals and among senior and junior physicians. CONCLUSIONS: A promising alternative to traditional WT for quality control and training assessment in colonoscopy is offered by AI-assisted computation of WTS.

Endobronchial ultrasound-guided cautery-assisted transbronchial mediastinal cryobiopsy in the diagnosis of fibrosing mediastinitis secondary to atypical sarcoidosis: a case report.

Background: Fibrosing mediastinitis (FM) secondary to atypical sarcoidosis (atypical presentation of sarcoidosis) is rarely reported at home and abroad. Its clinical manifestations represent a lack of specificity, and the initial diagnosis is frequently difficult. In particular, this case has multiple pulmonary nodules with mediastinal lymph node enlargement and bilateral pleural effusion, and pulmonary fibrosis still exists after treatment, which is inconsistent with any clinical stage of pulmonary sarcoidosis, further increasing the diagnostic difficulty. We retrospectively analyzed the clinical data of a case of FM secondary to atypical sarcoidosis diagnosed by endobronchial ultrasound-guided cautery-assisted transbronchial mediastinal cryobiopsy (EBUS-CA-TBMCB) in Chongqing University Fuling Hospital, to improve clinicians' attention to FM and understand that EBUS-CA-TBMCB remains an effective way of etiological diagnosis. Case Description: A 70-year-old man was hospitalized with cough and dyspnea for two months. After admission, through chest computed tomography (CT), ultrasound guided bilateral lung biopsy, left parietal pleural biopsy, and EBUS-CA-TBMCB, the final diagnosis was atypical sarcoidosis secondary FM. After taking glucocorticoid orally, the patient's condition improved significantly, and was discharged from the hospital. We continued following up outside the hospital, and the patient's condition was further improved. Conclusions: The diagnosis of FM is mainly based on typical imaging manifestations. When the contrast-enhanced chest CT finds localized or diffuse soft tissue density shadows around the mediastinum and pulmonary hilum with an irregular shape, with or without calcification, particular attention should be paid to exclude FM. EBUS-CA-TBMCB, as an improved minimally invasive method, can obtain enough tissue samples for pathological diagnosis, which may be the effective biopsy method for the etiology of FM to avoid missed diagnosis and misdiagnosis in the future.

Development and trends in research on hypertension and atrial fibrillation: A bibliometric analysis from 2003 to 2022.

BACKGROUND: This study aimed to comprehensively analyze research related to hypertension and atrial fibrillation, 2 common cardiovascular diseases with significant global public health implications, using bibliometric methods from 2003 to 2022. METHODS: From the Web of Science Core Collection database, literature on the theme of hypertension and atrial fibrillation was retrieved. Subsequently, comprehensive bibliometric analyses were conducted across multiple dimensions utilizing software tools such as VOSviewer, Citespace, Pajek, Scimago Graphica, and ClusterProfiler. These analyses encompassed examinations of the literature according to country/region, institution, authors, journals, citation relationships, and keywords. RESULTS: It revealed an increasing interest and shifting focus in research over the years. The analysis covered 7936 relevant publications, demonstrating a gradual rise in research activity regarding hypertension combined with atrial fibrillation over the past 2 decades, with a stable growth trend in research outcomes. Geographically, Europe and the Americas, particularly the United States, have shown the most active research in this field, while China has also gained importance in recent years. Regarding institutional contributions, internationally renowned institutions such as the University of Birmingham and the Mayo Clinic have emerged as core forces in this research direction. Additionally, Professor Lip Gregory, with his prolific research output, has stood out among numerous scholars. The American Journal of Cardiology has become a primary platform for publishing research related to hypertension and atrial fibrillation, highlighting its central role in advancing knowledge dissemination in this field. The research focus has shifted from exploring the pathophysiological mechanisms to investigating the treatment of complications and risk factors associated with hypertension and atrial fibrillation. Future research will focus on in-depth exploration of genetic and molecular mechanisms, causal relationship exploration through Mendelian randomization studies, and the application of machine learning techniques in prediction and treatment, aiming to promote the development of precision medicine for cardiovascular diseases. CONCLUSION: In conclusion, this study provides a comprehensive overview of the developmental trajectory of research on hypertension and atrial fibrillation, presenting novel insights into trends and future research directions, thus offering information support and guidance for research in this crucial field of cardiovascular medicine.

Skyrmion lattice formation and destruction mechanisms probed with TR-SANS.

Magnetic skyrmions are topologically protected, nanoscale whirls of the spin configuration that tend to form hexagonally ordered arrays. As a topologically non-trivial structure, the nucleation and annihilation of the skyrmion, as well as the interaction between skyrmions, varies from conventional magnetic systems. Recent works have suggested that the ordering kinetics in these materials occur over millisecond or longer timescales, which is unusually slow for magnetic dynamics. The current work investigates the skyrmion ordering kinetics, particularly during lattice formation and destruction, using time-resolved small angle neutron scattering (TR-SANS). Evaluating the time-resolved structure and intensity of the neutron diffraction pattern reveals the evolving real-space structure of the skyrmion lattice and the timeframe of the formation. Measurements were performed on three prototypical skyrmion materials: MnSi, (Fe,Co)Si, and Cu2OSeO3. To probe lattice formation and destruction kinetics, the systems were prepared in the stable skyrmion state, and then a square-wave magnetic field modulation was applied. The measurements show that the skyrmions quickly form ordered domains, with a significant distribution in lattice parameters, which then converge to the final structure; the results confirm the slow kinetics, with formation times between 10 ms and 99 ms. Comparisons are made between the measured formation times and the fundamental material properties, suggesting the ordering temperature, saturation magnetization and magnetocrystalline anisotropy may be driving the timeframes. Micromagnetic simulations were also performed and support a scaling of the kinetics with sample volume, a behavior which is caused by the reconciling of misaligned domains.

Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).

Histone chaperones serve a pivotal role in maintaining human physiological processes. They interact with histones in a stable manner, ensuring the accurate and efficient execution of DNA replication, repair and transcription. Retinoblastoma binding protein (RBBP)4 and RBBP7 represent a crucial pair of histone chaperones, which not only govern the molecular behavior of histones H3 and H4, but also participate in the functions of several protein complexes, such as polycomb repressive complex 2 and nucleosome remodeling and deacetylase, thereby regulating the cell cycle, histone modifications, DNA damage and cell fate. A strong association has been indicated between RBBP4/7 and some major human diseases, such as cancer, age­related memory loss and infectious diseases. The present review assesses the molecular mechanisms of RBBP4/7 in regulating cellular biological processes, and focuses on the variations in RBBP4/7 expression and their potential mechanisms in various human diseases, thus providing new insights for their diagnosis and treatment.

Progress and hotspot of diet or exercise therapy in the treatment of non-alcoholic fatty liver disease.

Introduction: The primary treatment for non-alcoholic fatty liver disease (NAFLD) is modifying lifestyle through dietary or exercise interventions. In recent decades, it has received increasing attention. However, the lack of bibliometric analysis has posed a challenge for researchers seeking to understand the overall trends in this field. Methods: As of February 3rd, 2024, 876 articles on treating NAFLD through diet or exercise therapy from 2013 to 2023 had been retrieved. Two software tools, VOSviewer and CiteSpace, were utilized to analyze the growth of publications, countries, institutions, authors, journals, citations, and keywords. Additionally, the keywords with strong citation burstiness were identified to determine the changes and future trends of research hotspots in this field. Results: China had the highest number of articles, followed by the United States and South Korea. Yonsei University and Nutrients were the institutions and journals with the most significant contributions. Professor Younossi Zobair M, from the United States, is the most prolific author in this field. Through analyzing the keywords, three research hotspots were identified: research on the pathogenesis of NAFLD, research on the treatment modalities of NAFLD, and research on the risk factors and diagnosis methods of NAFLD. In recent years, the research emphasis in this field has changed, suggesting that future research will focus on two frontier keywords: "oxidative stress" and "aerobic capacity." Conclusion: In the past eleven years, the attention in this field was still rising, and the authors, journals, countries and so on had formed a considerable cooperative relationship. There were also many highly influential and productive researchers in this field. It is speculated that new research will continue around "aerobic exercise" and "oxidative stress" in the future.

Effects of Ganjianglingzhu Decoction on Lean Non-Alcoholic Fatty Liver Disease in Mice Based on Untargeted Metabolomics.

Non-alcoholic fatty liver disease (NAFLD) is usually associated with obesity. However, it is crucial to recognize that NAFLD can also occur in lean individuals, which is frequently overlooked. Without an approved pharmacological therapy for lean NAFLD, we aimed to investigate whether the Ganjianglingzhu (GJLZ) decoction, a representative traditional Chinese medicine (TCM), protects against lean NAFLD and explore the potential mechanism underlying these protective effects. The mouse model of lean NAFLD was established with a methionine-choline-deficient (MCD) diet in male C57BL/6 mice to be compared with the control group fed the methionine-choline-sufficient (MCS) diet. After four weeks, physiological saline, a low dose of GJLZ decoction (GL), or a high dose of GJLZ decoction (GH) was administered daily by gavage to the MCD group; the MCS group was given physiological saline by gavage. Untargeted metabolomics techniques were used to explore further the potential mechanism of the effects of GJLZ on lean NAFLD. Different doses of GJLZ decoction were able to ameliorate steatosis, inflammation, fibrosis, and oxidative stress in the liver; GL performed a better effect on lean NAFLD. In addition, 78 candidate differential metabolites were screened and identified. Combined with metabolite pathway enrichment analysis, GL was capable of regulating the glucose and lipid metabolite pathway in lean NAFLD and regulating the glycerophospholipid metabolism by altering the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0). GJLZ may protect against the development of lean NAFLD by regulating glucose and lipid metabolism, inhibiting the levels of sn-3-O-(geranylgeranyl)glycerol 1-phosphate and lysoPC(P-18:0/0:0) in glycerophospholipid metabolism.

Effects of Rifampicin Plus Levofloxacin or Isoniazid on Immune Function of Patients with Pulmonary Tuberculosis.

Context: Due to the different effects of various drugs and the lack of authoritative and unified guidelines in clinical practice, the choice of therapeutic drugs for pulmonary tuberculosis (TB) remains controversial. Rifampicin, levofloxacin, and isoniazid are all anti-TB drugs. However, no comparative studies of the treatment effects of rifampicin + levofloxacin and rifampicin + isoniazid have occurred. Objective: The study intended to analyze the therapeutic effects of rifampicin + levofloxacin compared to rifampicin + isoniazid in the treatment of pulmonary TB to provide a clinical reference, which could provide new references for future clinical treatment of the disease. Design: The research team conducted a prospective controlled study. Setting: The study took place at Zibo Zhoucun District People's Hospital in Zibo, China. Participants: Participants were 100 patients with pulmonary TB admitted to the hospital between March 2021 and December 2022. Interventions: The research team assigned participants to one of two groups: (1) the intervention group, with 56 participants who received rifampicin + levofloxacin therapy, and (2) the control group, with 44 participants who received rifampicin + isoniazid. Outcome Measures: The research team measured: (1) clinical efficacy, (2) incidence of adverse reactions, (3) changes in inflammatory factors, (4) changes in immunoglobulins (Igs), and (5) changes in T lymphocyte subsets. Results: The intervention group's total effective rate for treatment was significantly higher than that of the control group (P = .049). However, no significant difference existed between the groups in the incidence of adverse reactions (P > .05). Postintervention, the intervention group's inflammatory factors-IL-6, TNF-α, hs-CRP, and ß-EP-were significantly lower and its immunoglobulins (Igs) G/A/M (IgG/A/M) were significantly higher than those of the control group (P < .05). In addition, the intervention group's T lymphocyte subpopulations of CD3+ and CD4+ and CD4+/CD8+ were significantly higher and CD8+ was significantly lower than those in the control group (P < .05). In other words, the intervention group had a better immune function. Conclusions: Compared with rifampicin + isoniazid, rifampicin + levofloxacin had a better clinical effect in the treatment of pulmonary TB and could effectively regulate patients' immune functions and inhibit inflammatory reactions. The current research team recommends that rifampicin + levofloxacin become the preferred treatment for pulmonary TB in the absence of a drug allergy.

Dermoscopy and Histopathology of Hyperkeratosis of Nipple and Areola: A Case Report.

We describe a case involving a 19-year-old female with who presented with bilateral nipple-areola brown patches persisting for five years. The diagnosis of hyperkeratosis of the nipple and areola (HNA) was established through dermoscopy and histopathology. The findings highlight the value of dermoscopy in the diagnosis and differentiation of HNA.

Erratum: FAM72A promotes glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.82949.].

Deep learning analysis for rapid detection and classification of household plastics based on Raman spectroscopy.

The overuse of plastics releases large amounts of microplastics. These tiny and complex pollutants may cause immeasurable damage to human social life. Raman spectroscopy detection technology is widely used in the detection, identification and analysis of microplastics due to its advantages of fast speed, high sensitivity and non-destructive. In this work, we first recorded the Raman spectra of eight common plastics in daily life. By adjusting parameters such as laser wavelength, laser power, and acquisition time, the Raman data under different acquisition conditions were diversified, and the corresponding Raman spectra were obtained, and a database of eight household plastics was established. Combined with deep learning algorithms, an accurate, fast and simple classification and identification method for 8 types of plastics is established. Firstly, the acquired spectral data were preprocessed for baseline correction and noise reduction, Then, four machine learning algorithms, linear discriminant analysis (LDA), decision tree, support vector machine (SVM) and one-dimensional convolutional neural network (1D-CNN), are used to classify and identify the preprocessed data. The results showed that the classification accuracy of the three machine learning models for the Raman spectra of standard plastic samples were 84%, 93% and 93% respectively. The 1D-CNN model has an accuracy rate of up to 97% for Raman spectroscopy. Our study shows that the combination of Raman spectroscopy detection techniques and deep learning algorithms is a very valuable approach for microplastic classification and identification.

Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

Comparative efficacy and safety of medical treatments for proximal humerus fractures: a systematic review and network meta-analysis.

BACKGROUND: Various surgical techniques and conservative therapies are useful tools for treating proximal humerus fractures (PHFs), but it is important to understand how to properly utilize them. Therefore, we performed a systematic review and network meta-analysis to compare and rank the efficacy and safety of medical treatments for PHF. METHODS: PubMed, Embase, the Cochrane Library, and the ClinicalTrials.gov databases were systematically searched for eligible randomized controlled trials (RCTs) from inception until June 2022. Conservative therapy-controlled or head-to-head RCTs of open reduction internal fixation (ORIF), intramedullary nailing (IMN), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (RTSA) used for the treatment of adult patients with PHF were included. The surface under the cumulative ranking (SUCRA) probabilities were applied to compare and rank the effects of medical treatments for PHF. RESULTS: Eighteen RCTs involving 1,182 patients with PHF were selected for the final analysis. Mostly baseline characteristics among groups were well balanced, and the imbalanced factors only included age, injury type, medial comminution, blood loss, and cognitive function in single trial. The SUCRA probabilities found that RTSA provided the best effect on the Constant-Murley score (SUCRA: 100.0%), and the disabilities of the arm, shoulder and hand (DASH) score (SUCRA: 99.0%). Moreover, HA (SUCRA: 85.5%) and RTSA (SUCRA: 68.0%) had a relatively better effect on health-related quality of life than the other treatment modalities. Furthermore, conservative therapy (SUCRA: 84.3%) and RTSA (SUCRA: 80.7%) were associated with a lower risk of secondary surgery. Finally, the best effects on the risk of complications are varied, including infection was observed with conservative therapy (SUCRA: 94.2%); avascular necrosis was observed in HA (SUCRA: 78.1%), nonunion was observed in RTSA (SUCRA: 69.6%), and osteoarthritis was observed in HA (SUCRA: 93.9%). CONCLUSIONS: This study found that RTSA was associated with better functional outcomes, while the comparative outcomes of secondary surgery and complications varied. Optimal treatment for PHF should consider patient-specific factors.

Screening, cloning, immobilization and application prospects of a novel ß-glucosidase from the soil metagenome.

The soil environment for straw return is a rich and valuable library containing many microorganisms and proteins. In this study, we aimed to screen a high-quality ß-glucosidase (BGL) from the soil metagenomic library and to overcome the limitation of the low extraction rate of resveratrol in Polygonum cuspidatum. This includes the construction of a soil metagenomic library, screening of BGL, bioinformatics analysis, cloning, expression, immobilization, enzymatic property analysis, and application for the transformation of polydatin. The results showed that the soil metagenomic library of straw return was successfully constructed, and a novel BGL was screened. The identified 1356 bp long BGL belonged to the glycoside hydrolase 1 (GH1) family and was named Bgl1356. After successful cloning and expression of Bgl1356, it was immobilized using chitosan. The optimum temperature of immobilized Bgl1356 was 50 °C, and the pH was 5. It exhibited good tolerance for various metal ions (CO2+, Ni2+, Cu2+, Mn2+, Na2+, Ca2+, and Ag+) and organic solvents (DMSO, Triton-X-10, and ethanol). Enzymatic kinetics assays showed that Bgl1356 had good affinity for the substrate, and the specific enzyme activity was 234.03 U/mg. The conversion rate of polydatin by immobilized Bgl1356 was 95.70 ± 1.08%, facilitating the production of high amounts of resveratrol. Thus, this paper reports a novel temperature-, organic solvent-, and metal ion-tolerant BGL that has good application prospects in the pharmaceutical industry.

Relationship Between Dyadic Coping with Anxiety and Depression in Infertile Couples: Gender Differences and Dyadic Interaction.

Background: This study aims to examine the relationship between anxiety and depression and dyadic coping in infertile couples, exploring gender differences and dyadic interactions in these associations. Methods: A cross-sectional study was conducted involving 288 couples recruited from the First Affiliated Hospital of Lanzhou University between November 2021 and November 2022. The Dyadic Coping Scale, Anxiety Scale, and Depression Scale were utilized to measure dyadic coping, anxiety, and depression, respectively. The Actor-Partner Interdependence Model was used to analyze the actor effect and partner effect. Results: Wives exhibited significantly higher anxiety and depression scores compared to husbands (p<0.001). No statistically significant difference was found in dyadic coping between wives and husbands. Positive dyadic coping in infertile couples had significant actor effects on anxiety and depression (p<0.05) and partner effects (p<0.05). Positive dyadic coping negatively predicted anxiety and depression of oneself and one's partner. Negative dyadic coping in infertile couples also had significant actor effects on anxiety and depression (p<0.05) and partner effects (p<0.05). Negative dyadic coping positively predicted anxiety and depression of oneself and one's partner. Conclusion: The dyadic coping style of infertile couples has both actor and partner effects on their own and their partner's anxiety and depression. Anxiety and depression in infertile couples are influenced by their own and their partner's dyadic coping style, respectively. Therefore, dyadic coping serves as an important indicator for predicting psychological outcomes in these couples.