Unveiling the crucial role of ferroptosis in host resistance to streptococcus agalactiae infection.

IL-1ß represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1ß in the process of ferroptosis. However, the relationship between IL-1ß and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1ß induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1ß is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1ß playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis.

Analysis of odontoid parameters in adolescent idiopathic scoliosis patients with different curve types.

Introduction: Odontoid incidence (OI) is an important parameter that has recently been developed. However, there are currently no studies on OI in adolescent idiopathic scoliosis (AIS) patients. We aimed to examine the significance of OI in describing cervical sagittal alignment in AIS patients, explore the differences in cervical sagittal parameters among these patients with different curve types, and investigate the correlations between coronal deformity and cervical sagittal parameters in AIS patients. Methods: The whole-spine anteroposterior and lateral plain radiographs of AIS patients were retrospectively analyzed. The parameters, including OI, odontoid tilt (OT), C2 slope, cervical lordosis (CL), T1 slope (T1S), and others, were measured. The AIS patients were grouped based on different curve types. Measurement parameters were compared between different groups. Pearson correlation analysis was performed for cervical sagittal parameters and Cobb angle. Results: Ninety AIS patients were included, consisting of 14 males and 76 females. The main thoracic curve group exhibited a smaller OI compared to the main thoracolumbar/lumbar curve group (P < 0.05). In the AIS patients with a main thoracic curve, there was a significant correlation between Cobb angle and OI (r = -0.371, p < 0.01). The odontoid parameters exhibited significant correlations with several classic cervical sagittal parameters in AIS patients with different curve types. The validation of the formula CL = 0.36 × OI-0.67 × OT-0.69 × T1S showed a significant correlation (correlation coefficient = 0.917) between the actual measurements and the predicted values, with a determination coefficient of 0.842. Conclusion: There may be a difference in OI between AIS patients with a main thoracic curve and those with a main thoracolumbar/lumbar curve. Odontoid parameters could be used to describe cervical sagittal alignment in AIS patients with different curve types.

An exploratory clinical study of ß-glucan combined with camrelizumab and SOX chemotherapy as first-line treatment for advanced gastric adenocarcinoma.

Background: ß-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of ß-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. Methods: This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received ß-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy. Results: A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum. Conclusions: This preliminary study demonstrates that ß-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. Clinical Trial Registration: Chinese Clinical Trials Registry, identifier ChiCTR2100044088.

Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance.

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulfite sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

Nicotinamide N-methyltransferase (NNMT): A key enzyme in cancer metabolism and therapeutic target.

Emerging research has positioned Nicotinamide N-methyltransferase (NNMT) as a key player in oncology, with its heightened expression frequently observed across diverse cancers. This increased presence is tightly linked to tumor initiation, proliferation, and metastasis. The enzymatic function of NNMT is centered on the methylation of nicotinamide (NAM), utilizing S-adenosylmethionine (SAM) as the methyl donor, which results in the generation of S-adenosyl-L-homocysteine (SAH) and methyl nicotinamide (MNAM). This metabolic process reduces the availability of NAM, necessary for Nicotinamide adenine dinucleotide (NAD+) synthesis, and generates SAH, precursor to homocysteine (Hcy). These alterations are theorized to foster the resilience, expansion, and invasiveness of cancer cells. Furthermore, NNMT is implicated in enhancing cancer malignancy by affecting multiple signaling pathways, such as phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT), cancer-associated fibroblasts (CAFs) and 5-Methyladenosine (5-MA), epithelial-mesenchymal transition (EMT), and epigenetic mechanisms. Upregulation of NNMT metabolism plays a key role in the formation and maintenance of the tumour microenvironment. While the use of small molecule inhibitors and RNA interference (RNAi) to target NNMT has shown therapeutic promise, the full extent of NNMT's influence on cancer is not yet fully understood, and clinical evidence is limited. This article systematically describes the relationship between the functional metabolism of NNMT enzymes and the cancer and tumour microenvironments, describing the mechanisms by which NNMT contributes to cancer initiation, proliferation, and metastasis, as well as targeted therapies. Additionally, we discuss the future opportunities and challenges of NNMT in targeted anti-cancer treatments.

Combination Therapy With CGF and Microneedling-Assisted Compound Betamethasone for Resistant Alopecia Areata: APilot Study.

BACKGROUND: Alopecia areata (AA), an autoimmune disorder characterized by hair loss, can be particularly difficult to manage when patients do not respond to standard therapeutic approaches such as topical or injectable corticosteroids, contact immunotherapy, and systemic treatments. In instances where these conventional therapies prove ineffective, alternative or adjunctive treatments are sought. Concentrated growth factor (CGF) and microneedling (MN)-assisted drug delivery are promising methods for the treatment of different dermatological diseases. OBJECTIVE: This study aimed to assess the practical benefits and the safety aspects of utilizing a dual treatment approach involving CGF and MN-assisted compound betamethasone for patients suffering from resistant AA that are unresponsive to conventional medical interventions. MATERIAL AND METHODS: This retrospective study was based on evaluations of seven patients with refractory AA treated with CGF and MN-assisted compound betamethasone from July 2021 to December 2023. The efficacy of treatment was assessed by extents of hair regrowth percentages of involved areas. RESULTS: Among the seven enrolled patients with refractory AA, a notable outcome was observed where one patient (14.3%) achieved a regrowth of hair by over 50%, while six patients (85.7%) exhibited complete recovery without any systemic or local adverse effects. Furthermore, the difference in SALT scores between baseline, and the final visit for all patients was found to be statistically significant, substantiating the therapeutic efficacy of the intervention employed. CONCLUSION: The present study demonstrated that the synergistic application of CGF in conjunction with MN-assisted compound betamethasone may constitute a promising and well-tolerated therapeutic modality for refractory AA, offering a potentially efficacious and safe treatment alternative.

Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.

BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial.

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

A scoring-based clinical grading model for xanthelasma palpebrarum: predicting treatment frequency and prognosis.

Xanthelasma palpebrarum is one of the most common cutaneous xanthomas in humans. Currently, there are various methods available for treating xanthelasma palpebrarum, but the high treatment frequency and recurrence rate remain significant challenges for patients. Therefore, it is necessary to establish a reasonable and effective clinical grading system to guide the diagnosis and treatment of xanthelasma palpebrarum. We developed a clinical scoring system related to local injection of pingyangmycin for the treatment of xanthelasma palpebrarum, which can be used to predict early prognosis and treatment outcomes in patients. We collected and retrospectively studied 246 outpatient cases of xanthelasma palpebrarum treated with local injection of pingyangmycin in the Department of Plastic Surgery at Shanghai East Hospital from February 2020 to August 2022. Potential independent risk factors for adverse outcomes (recurrence or non-recurrence) were considered in univariate and multivariate logistic regression models. Predictive factors were determined based on the multivariate logistic regression model and Cox model, and a scoring grading system was established. External validation was conducted on an independent cohort of 110 patients. Based on logistic regression analysis, the number, area, and color of lesions were identified as significant predictive indicators (P < 0.05), with respective AUCs of 0.710, 0.799, and 0.755. The Cox model established hazard ratios for four new severity indicators of xanthelasma palpebrarum: hyperlipidemia, number of lesions, lesion area, and lesion grayscale value. Based on these findings, a new clinical grading model was developed, which was validated to be effective in the external cohort. The new scoring-based clinical predictive model can effectively predict the number of pingyangmycin injection treatments and prognosis in patients with xanthelasma palpebrarum. It holds promise for broader application in clinical practice.

ß-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). ß-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received ß-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. RESULTS: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0-6.6] and 9.8 months [95% CI: 7.2-12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. CONCLUSION: ß-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.

Economic analysis of hydrogen energy systems: A global perspective.

In the realm of renewable energy, the integration of wind power and hydrogen energy systems represents a promising avenue towards environmental sustainability. However, the development of cost-effective hydrogen energy storage solutions is crucial to fully realize the potential of hydrogen as a renewable energy source. By combining wind power generation with hydrogen storage, a comprehensive hydrogen energy system can be established. This study aims to devise a physiologically inspired optimization approach for designing a standalone wind power producer that incorporates a hydrogen energy system on a global scale. The optimization process considers both total cost and capacity loss to determine the optimal configuration for the system. The optimal setup for an off-grid solution involves the utilization of eight distinct types of compact horizontal-axis wind turbines. Additionally, a sensitivity analysis is conducted by varying component capital costs to assess their impact on overall cost and load loss. Simulation results indicate that at a 15 % loss, the cost of energy (COE) is $1.3772, while at 0 % loss, it stands at $1.6908. Capital expenses associated with wind turbines and hydrogen storage systems significantly contribute to the overall cost. Consequently, the wind turbine-hydrogen storage system emerges as the most cost-effective and reliable option due to its low cost of energy.

Global Trends in Melanoma Burden: A Comprehensive Analysis from the Global Burden of Disease Study, 1990-2021.

BACKGROUND: Melanoma, a significant global health concern, has shown evolving epidemiological trends. Accurate estimation of melanoma's burden is essential for public health strategies and interventions. OBJECTIVES: This study aims to estimate the incidence, mortality, and disability-adjusted life years (DALYs) for melanoma, stratified by region, gender, and age group, from 1990 to 2021. METHODS: Using data from the Global Burden of Disease (GBD) 2021, we analyzed melanoma incidence, mortality rates, and DALYs in 204 countries from 1990 to 2021. These metrics were age-standardized and stratified by age, sex, Socio-Demographic Index (SDI), region, and country. The estimated annual percentage change (EAPC) was calculated to track temporal trends. RESULTS: Our study shows a substantial global increase in melanoma incidence, with significant disparities between genders and age groups. Higher SDI regions had increased incidence rates, while global mortality declined, likely due to improved detection and treatment. LIMITATIONS: The reliance on estimates and models may introduce bias due to variability in disease definitions, diagnostic criteria, and data collection methods. CONCLUSION: This study underscores the dynamic nature of melanoma's burden and the need for targeted, age-specific, and gender-specific interventions. Continued research is essential to address the growing challenges posed by melanoma.

Sex differences in the association between chest computed tomography-defined sarcopenia and cardiovascular risk factors among inpatients.

Background: While sarcopenia has been found to be associated with increased risks of cardiovascular diseases (CVDs), evidence exploring sex-related differences remains insufficient. This study aimed to investigate the differences in how often sarcopenia occurs in each sex, as determined by skeletal muscle area (SMA) in chest CT images, and its association with CVD common risk factors. Methods: This cross-sectional study involved 1,340 inpatients from the Department of Geriatrics of Renji Hospital, affiliated to Shanghai Jiaotong University School of Medicine. Data on age, sex, body mass index (BMI), smoking status, disease history, and clinical parameters were collected. Sarcopenia was defined using chest CT images with a cut-off value of T12-SMA/height2 <25.75 cm2/m2 in male patients and <20.16 cm2/m2 in female patients. Cardiovascular risk was assessed using the Framingham risk score (FRS). The association between T12-SMA/height2-defined sarcopenia and CVD risk factors by sex was evaluated using a multivariate logistic regression analysis. Results: The overall prevalence of T12-SMA/height2-defined sarcopenia (<25.75 cm2/m2 for male patients, <20.16 cm2/m2 for female patients) was 54.03%, with 48.09% in male patients and 63.19% in female patients. The proportion of male patients with high CVD risk was greater than that of female patients. The multivariate analysis revealed that T12-SMA/height2-defined sarcopenia was independently associated with age (in male patients only), systolic blood pressure (SBP), cholesterol, and high-density lipoprotein cholesterol (HDL-C) among the six FRS cardiovascular risk indices. Conclusion: Our results suggest that T12-SMA/height2-defined sarcopenia was more prevalent in male patients than in female patients. Sarcopenia was associated with higher levels of SBP and HDL-C and lower levels of cholesterol. Increasing age had a more significant effect on CVD risk in male patients.

Guided Heterostructure Growth of CoFe LDH on Ti3C2Tx MXene for Durably High Oxygen Evolution Activity.

Heterostructures of layered double hydroxides (LDHs) and MXenes have shown great promise for oxygen evolution reaction (OER) catalysts, owing to their complementary physical properties. Coupling LDHs with MXenes can potentially enhance their conductivity, stability, and OER activity. In this work, a scalable and straightforward in situ guided growth of CoFeLDH on Ti3C2Tx is introduced, where the surface chemistry of Ti3C2Tx dominates the resulting heterostructures, allowing tunable crystal domain sizes of LDHs. Combined simulation results of Monte Carlo and density functional theory (DFT) validate this guided growth mechanism. Through this way, the optimized heterostructures allow the highest OER activity of the overpotential = 301 mV and Tafel slope = 43 mV dec-1 at 10 mA cm-2, and a considerably durable stability of 0.1% decay over 200 h use, remarkably outperforming all reported LDHs-MXenes materials. DFT calculations indicate that the charge transfer in heterostructures can decrease the rate-limiting energy barrier for OER, facilitating OER activity. The combined experimental and theoretical efforts identify the participation role of MXene in heterostructures for OER reactions, providing insights into designing advanced heterostructures for robust OER electrocatalysis.

Effect of thermal and non-thermal processing methods on the Structural and Functional Properties of Whey Protein from Donkey Milk.

This study evaluated the impact of thermal, ultrasonication, and UV treatment on the structural and functional properties of whey proteins from donkey milk (DWP). Whey proteins exhibited notable stability in non-heat-treated environments, while their structural and functional characteristics were notably impacted by excessive heat treatment. The application of high-temperature long-time thermal treatment (HTLT) resulted in a decrease in fluorescence intensity, foaming and emulsification stability, and considerable damage to the active components of the proteins. Specifically, the preservation of lysozyme activity was only 23%, and lactoferrin and immunoglobulin G exhibited a significant loss of 70% and 77%, respectively. Non-thermal treatment methods showed superior efficacy in preserving the active components in whey proteins compared with heat treatment. Ultrasonic treatment has demonstrated a notable capability in diminishing protein particle size and turbidity, and UV treatment has been observed to have the ability to oxidize internal disulfide bonds within proteins, consequently augmenting the presence of free sulfhydryl groups, which were beneficial to foaming and emulsification stability. This study not only offers a scientific basis for the processing and application of DWP but also serves as a guide to produce dairy products, aiding in the development of dairy products tailored to specific health functions.

Study on Preclinical Safety and Toxic Mechanism of Human Umbilical Cord Mesenchymal Stem Cells in F344RG Rats.

Mesenchymal stem cells have made remarkable progress in recent years. Many studies have reported that human umbilical cord mesenchymal stem cells (hUC-MSCs) have no toxicity, but thromboembolism appeared in patients treated with hUC-MSCs. Therefore, people are still worried about the safety of clinical application. The study aims to determine the safety, potential toxic mechanism and biodistribution of hUC-MSCs. F344RG rats were given 5 or 50 million cells/kg of hUC-MSCs by single administration in compliance with Good Laboratory Practice standards. Standard toxicity was performed. RNA sequencing was then performed to explore the potential toxic mechanisms. In parallel, the biodistribution of hUC-MSCs was examined. The dose of 5 million cells/kg hUC-MSCs had no obvious toxicity on symptom, weight, food intake, hematology, serum biochemistry, urine biochemistry, cytokines, and histopathology. However, blood-tinged secretions in the urethral orifice and 20% mortality occurred at 50 million cells/kg. Disseminated intravascular coagulopathy (DIC) is the leading cause of death. hUC-MSCs significantly upregulated complement and coagulation cascade pathways gene expression, resulting in DIC. Besides, hUC-MSCs upregulated fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2. hUC-MSCs survived in rats for less than 28 days, no hUC-MSC was detected in tissues outside the lungs. There was no toxicity in F344RG rats at 5 million cells/kg, but some toxicities were detected at 50 million cells/kg. hUC-MSCs significantly upregulated complement and coagulation cascade pathways, upregulated the expression of fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2, to inhibit fibrinolytic system, caused DIC, which provided a new insight into the toxic mechanism of hUC-MSCs.

[Cold reducing acupuncture as adjunctive therapy for wrist joint disorder of active rheumatoid arthritis with dampness-heat obstruction：a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between cold reducing acupuncture combined with western medication and western medication alone for wrist joint disorder of active rheumatoid arthritis (RA) with dampness-heat obstruction. METHODS: A total of 80 patients with wrist joint disorder of active RA with dampness-heat obstruction were randomly divided into a combination group (40 cases, 3 cases dropped out) and a western medication group (40 cases, 3 cases dropped out). The western medication group was treated with methotrexate tablets, 15 mg each time, once a week. The combination group was treated with cold reducing acupuncture at bilateral Hegu (LI 4), Houxi (SI 3), Waiguan (TE 5), etc. on the basis of the western medication group, once a day, 5 times a week. Both groups were treated for 8 weeks. The pain visual analogue scale (VAS) score, swelling score, morning stiffness score, Cooney wrist joint function score, ultrasound of wrist joint and serum level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) before and after treatment were compared in the two groups. RESULTS: After treatment, the pain VAS scores, swelling scores, morning stiffness scores, grey scale ultrasound (GSUS) grade of synovitis, power doppler ultrasound (PDUS) grade of synovitis of wrist joint and serum levels of CRP and ESR in the two groups were reduced compared with those before treatment (P<0.05), the Cooney wrist joint function scores were increased compared with those before treatment (P<0.05); the pain VAS score, swelling score, PDUS grade of synovitis of wrist joint and serum level of CRP and ESR in the combination group were lower than those in the western medication group (P<0.05), the Cooney wrist joint function score was higher than that in the western medication group (P<0.05). CONCLUSION: Cold reducing acupuncture combined with western medication could improve clinical symptoms and joint function, reduce inflammatory response in patients with wrist joint disorder of active RA with dampness-heat obstruction, and the efficacy is better than that of western medication alone.

[Corrigendum] DJ­1 is involved in the peritoneal metastasis of gastric cancer through activation of the Akt signaling pathway.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the western blot data shown for the MMP­9 experiment in Fig. 4 on p. 1493 were strikingly similar to the western blots shown for the total­Akt experiments in Fig. 6 on p. 1494. After having re­examined their original data files, the authors realized that Fig. 6 had been inadvertently assembled incorrectly. The revised version of Fig. 6, containing the correct data for the total­Akt experiments, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 31: 1489­1497, 2014; DOI: 10.3892/or.2013.2961].

The crosstalk between DNA-damage responses and innate immunity.

DNA damage is typically caused during cell growth by DNA replication stress or exposure to endogenous or external toxins. The accumulation of damaged DNA causes genomic instability, which is the root cause of many serious disorders. Multiple cellular organisms utilize sophisticated signaling pathways against DNA damage, collectively known as DNA damage response (DDR) networks. Innate immune responses are activated following cellular abnormalities, including DNA damage. Interestingly, recent studies have indicated that there is an intimate relationship between the DDR network and innate immune responses. Diverse kinds of cytosolic DNA sensors, such as cGAS and STING, recognize damaged DNA and induce signals related to innate immune responses, which link defective DDR to innate immunity. Moreover, DDR components operate in immune signaling pathways to induce IFNs and/or a cascade of inflammatory cytokines via direct interactions with innate immune modulators. Consistently, defective DDR factors exacerbate the innate immune imbalance, resulting in severe diseases, including autoimmune disorders and tumorigenesis. Here, the latest progress in understanding crosstalk between the DDR network and innate immune responses is reviewed. Notably, the dual function of innate immune modulators in the DDR network may provide novel insights into understanding and developing targeted immunotherapies for DNA damage-related diseases, even carcinomas.