Rosa roxburghii Tratt juice inhibits NF-κB and increases IL-2 to alleviates the Foxp3-mediated Tregs imbalance in the peripheral blood of arseniasis patients.

Arsenic can cause immune inflammation, which is the basis of arsenic-induced damage to multiple organs and systems. Forkhead box P3 (Foxp3)-labelled CD4+CD25+ regulatory T cells (Tregs) play an essential role in maintaining immune homeostasis. Nuclear factor-κb (NF-κB) and Interleukin-2 (IL-2) are critical regulators of Foxp3. Rosa roxburghii Tratt (RRT) is an edible medicinal plant with anti-inflammation effects. In this study, a control group (n = 41) and an arseniasis group (n = 209) were recruited, and screened subjects from the arseniasis patients for RRTJ (n = 46) or placebo (n = 43) to explore the possible mechanism by which RRT alleviates immune inflammation. The results indicated that RRTJ can inhibits NF-κB and increases IL-2, and alleviates the Foxp3-mediated Tregs imbalance in the peripheral blood of arseniasis patients. In summary, these findings suggest a novel intervention or therapeutic target for immune inflammation in arseniasis patients and provide new evidence that RRTJ inhibits immune inflammation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01384-0.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

Abstracts of randomized controlled trials in pediatric dentistry: reporting quality and spin.

BACKGROUND: Abstracts provide readers a concise and readily accessible information of the trials. However, poor reporting quality and spin (misrepresentation of research findings) can lead to an overestimation in trial validity. This methodological study aimed to assess the reporting quality and spin among randomized controlled trial (RCT) abstracts in pediatric dentistry. METHODS: We hand-searched RCTs in five leading pediatric dental journals between 2015 and 2021. Reporting quality in each abstract was assessed using the original 16-item CONSORT for abstracts checklist. Linear regression analyses were performed to identify factors associated with reporting quality. We evaluated the presence and characteristics of spin only in abstracts of parallel-group RCTs with nonsignificant primary outcomes according to pre-determined spin strategies. RESULTS: One hundred eighty-two abstracts were included in reporting quality evaluation. The mean overall quality score was 4.57 (SD, 0.103; 95% CI, 4.36-4.77; score range, 1-10). Only interventions, objective, and conclusions were adequately reported. Use of flow diagram (P < 0.001) was the only significant factor of higher reporting quality. Of the 51 RCT abstracts included for spin analysis, spin was identified in 40 abstracts (78.4%), among which 23 abstracts (45.1%) had spin in the Results section and 39 in the Conclusions Sect. (76.5%). CONCLUSIONS: The reporting quality of RCT abstracts in pediatric dentistry is suboptimal and the prevalence of spin is high. Joint efforts are needed to improve reporting quality and minimize spin.

'Spin' among abstracts of randomised controlled trials in sleep medicine: A research-on-research study.

STUDY OBJECTIVES: 'Spin', using reporting strategies to distort study results, can mislead readers of medical research. This study aimed to evaluate the prevalence and characteristics of 'spin' among randomised controlled trial (RCT) abstracts published in sleep medicine journals, and to identify factors associated with its presence and severity. METHODS: The search for RCTs published between 2010 and 2020 were conducted in seven reputable journals of sleep medicine. Abstracts of RCTs with statistically nonsignificant primary outcomes were included and analysed for 'spin', according to pre-determined 'spin' strategies. Chi-square tests or logistic regression analyses were performed to detect the association between characteristics of included abstracts and the presence and severity of 'spin'. RESULTS: A total of 114 RCT abstracts were included in this study, of which 89 (78.1%) were identified as having at least one type of 'spin' strategy. Sixty-six abstracts (57.9%) had 'spin' in the Results section, 82 (71.9%) abstracts presented with 'spin' in the Conclusions section. The presence of 'spin' varied significantly among RCTs based on the different categories of research area (P=0.047) and the statistician involvement (P=0.045). Furthermore, research area (P=0.019) and funding status (P=0.033) were significant factors associated with the severity of 'spin'. CONCLUSIONS: The prevalence of 'spin' is high among RCT abstracts in sleep medicine. This raise the need for researchers, editors and other stakeholders to be aware of the issue of 'spin' and make joint efforts to eliminate it in future publications.

Novel roles of RNA-binding proteins in drug resistance of breast cancer: from molecular biology to targeting therapeutics.

Therapy resistance remains a huge challenge for current breast cancer treatments. Exploring molecular mechanisms of therapy resistance might provide therapeutic targets for patients with advanced breast cancer and improve their prognosis. RNA-binding proteins (RBPs) play an important role in regulating therapy resistance. Here we summarize the functions of RBPs, highlight their tremendously important roles in regulating therapy sensitivity and resistance and we also reveal current therapeutic approaches reversing abnormal functions of RBPs in breast cancer.

Abstracts of randomized controlled trials in the field of dentofacial trauma: Reporting quality and spin.

BACKGROUND/AIM: Abstracts of randomized controlled trials (RCTs) provide a summary of the entire trial report. Their transparent, detailed, and accurate reporting is essential for clinical decision-making and evidence-based dental practice. The aim of this study was to assess the reporting quality and prevalence of spin in abstracts of RCTs in the field of dentofacial trauma. MATERIALS AND METHODS: The PubMed database was searched to identify RCT reports published between 2017 and 2021 in the field of dentofacial trauma. The reporting quality of abstracts was assessed according to the 16-item CONSORT for Abstracts checklist and measured with an overall quality score (OQS, range: 0-16). Linear regression analyses were used to identify factors associated with reporting quality. Among the included RCTs, parallel-group RCTs with non-significant primary outcomes were selected for spin assessment using predefined spin strategies. RESULTS: One hundred and twelve eligible abstracts were identified and included. The mean OQS was 4.51 (SD, 1.35; 95% CI, 4.26-4.76). Abstracts with more than 250 words (p = .004) and a structured format (p = .032) had significantly better reporting quality. Of the 30 abstracts that were eligible for spin assessment, spin was identified in 23 (76.7%). Among these, spin was observed in the Conclusions sections of 22 abstracts (73.3%) and the Results sections of 9 abstracts (30.0%). CONCLUSIONS: Among RCT abstracts in the field of dentofacial trauma, the reporting quality was sub-optimal and the prevalence of spin was relatively high. Strict adherence to the CONSORT for Abstracts guidelines is needed to ensure complete and transparent reporting. Relevant stakeholders need to make concerted efforts to avoid spin.

Caries risk assessment-related knowledge, attitude, and behaviors among Chinese dentists: a cross-sectional survey.

OBJECTIVES: To investigate caries risk assessment (CRA)-related knowledge, attitudes, and practices among dentists in China, to describe their subjective ratings of the significance of specific caries risk factors and to identify factors associated with the level of knowledge, attitudes, and use of CRA in routine clinical practice. MATERIALS AND METHODS: A cross-sectional anonymous online questionnaire survey was performed. The questionnaire was distributed via WeChat (Tencent, Shenzhen, China) to practicing dentists between November 25 and December 25, 2021. For participant recruitment, we employed purposive and snowball sampling techniques. Data were collected using a specialized web-based survey tool ( www.wjx.cn ) and analyzed with descriptive statistics and regression analyses. RESULTS: A total of 826 valid questionnaires were collected. Only 292 (35.4%) respondents used CRA in routine practice, among whom a majority (243, 83.2%) did not use a specific CRA tool. The routine use of CRA was associated with the type of practicing office, attendance of caries-related lectures, the habit of reading caries-related literature, geographic location, and the total knowledge score. The mean total knowledge score was 3.13 (score range: 0 to 6). Knowledge levels were related to several sociodemographic characteristics, including geographic location, the type of practicing office, attendance of caries-related lectures and the habit of reading caries-related literature. The risk factor deemed most important was "current oral hygiene." CONCLUSIONS: Caries risk assessment has not widely entered clinical practice in China. The level of CRA-related knowledge among dentists was generally suboptimal. CLINICAL RELEVANCE: Strengthening CRA-related education may allow practitioners to develop a better understanding of caries risk assessment and hence promote its implementation.

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk.

Background and Purpose: Arsenic exposure can lead to skin lesions and multiple organ damage, which are not easily reversible and for which there is no effective therapeutics. Identification of reliable epigenetic markers is essential for early recognition of arsenic poisoning risk. Anomalous DNA methylation of immune homeostasis regulator FOXP3 is a critical mechanism for triggering arsenic poisoning. This study aims to explore the value of FOXP3 methylation in the identification of arsenic poisoning risk.Methods: 88 arsenic poisoning subjects and 41 references were recruited. Urinary arsenic contents and FOXP3 methylation in PBLCs was measured by ICP-MS and pyrosequencing, respectively.Results: The results showed that the elevated FOXP3 methylation in PBLCs were associated with the increased levels of urinary arsenic and were positively associated with the increased risk of arsenic poisoning and its progression. The result of mediation analysis revealed that 24.3% of the effect of arsenic exposure on the risk of arsenic poisoning was mediated by increased FOXP3 methylation. Additionally, we constructed a nomogram model with FOXP3 methylation as an epigenetic predictor to assess the probability of individual arsenic poisoning. The model showed a robust ability in the discrimination of arsenic poisoning risk, with an area under receiver operating characteristics curve of 0.897(0.845-0.949) and more than 70% accuracy. The calibration curves and the Harrell concordance index showed that the consistency rate between the probability predicted by the nomogram model and the actual probability is 89.7%.Conclusions: Taken together, we found the great potential of FOXP3 methylation for the identification of arsenic poisoning risk and provided a new approach to the application of epigenetic markers in accurately quantifying the risk of adverse outcomes.

An inclined tower crane suited to bridge tower construction.

A new type of tower crane which could transform its tower body is presented. The inclined tower crane body can be tilted at some angle, which suits the construction of buildings with inclined architectural outlines, especially for the construction of bridge towers. The working principle and the design of the critical components are presented, two adjustable anchorages could pull the tower body section beneath the top anchorage closer to the construction region, and the related section of the tower body could change from vertical to inclined, while the free section of the tower body remains vertical. Finite element analysis is performed to compare with the traditional tower crane, the difference of the reaction force of the top anchorage is minor. Kinematic and dynamic analysis is carried out to simulate the working process of tilting, mechanical and kinematic parameters of key parts are obtained. At last, the experiment of a full-scale tower crane which could tilt 6° is carried out, and the experimental data validate the feasibility of this new type of tower crane.

Successful treatment of Talaromyces marneffei pneumonia in a HIV-negative renal transplantation recipient: A case report.

RATIONALE: Talaromyces marneffei causes life-threatening opportunistic fungal infections in immunocompromised patients. It often has a poorer prognosis in non-human immunodeficiency virus (HIV)-infected than in HIV-infected individuals because of delayed diagnosis and improper treatment. PATIENT CONCERNS: A 51-year-old man presented with complaints of pyrexia, cough, and expectoration that had lasted for 15 day. This patient has been taking anti-rejection medication since kidney transplant in 2011. DIAGNOSIS: T marneffei pneumonia; post renal transplantation; renal insufficiency; hypertension. INTERVENTIONS: Intravenous moxifloxacin was administered on admission. After the etiology was established, moxifloxacin was discontinued and replaced with voriconazole. The tacrolimus dose was adjusted based on the blood concentration of tacrolimus and voriconazole. OUTCOMES: The patient was successfully treated and followed-up without recurrence for 1 year. LESSONS: A high degree of caution should be maintained for the possibility of T marneffei infection in immunodeficient non-HIV patients who live in or have traveled to T marneffei endemic areas. Early diagnosis and appropriate treatment can prevent progression of T marneffei infection and achieve a cure. Metagenomic next-generation sequencing (mNGS) can aid the physician in reaching an early pathogenic diagnosis. Close monitoring of tacrolimus and voriconazole blood levels during treatment remains a practical approach at this time.

Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3.

Most cancer-related deaths are a result of metastasis. The development of small molecular inhibitors reversing cancer metastasis represents a promising therapeutic opportunity for cancer patients. This pan-cancer analysis identifies oncogenic roles of membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3), which is crucial for cancer metastasis. Small molecules targeting PITPNM3 must be explored further. Here, PITPNM3-selective small molecular inhibitors are reported. These compounds exhibit target-specific inhibition of PITPNM3 signaling, thereby reducing metastasis of breast cancer cells. Besides, by using nanoparticle-based delivery systems, these PITPNM3-selective compounds loaded nanoparticles significantly repress metastasis of breast cancer in mouse xenograft models and organoid models. Notably, the results establish an important metastatic-promoting role for PITPNM3 and offer PITPNM3 inhibition as a therapeutic strategy in metastatic breast cancer.

Pyopneumothorax Caused by Trichomonas tenax and Porphyromonas endodontalis Coinfection in a Patient with Previous Cerebral Infarction: A Case Report and Literature Review.

Background: Even with the advent of NGS and PCR diagnostic tools, cases of chest infections caused by Trichomonas are still very rare. Such pathogens are less likely to be considered by clinicians. These cases frequently involve the pleura and lead to pneumothorax, hydropneumothorax, or pyopneumothorax, making the disease severe. Case Presentation: A 69-year-old man diagnosed with cerebral infarction a year ago sought medical attention for right-sided pyopneumothorax and respiratory failure. The pathogen found in the pleural fluid was highly suspected to be Trichomonas tenax (T. tenax). Pleural fluid mNGS confirmed T. tenax and Porphyromonas endodontalis coinfection. Metronidazole combined with piperacillin tazobactam was administered to counteract infection. Simultaneously, closed chest drainage and thoracoscopic release of pleural adhesions were performed. The patient was cured, discharged from the hospital, and was in good condition after six months of follow-up. Conclusion: When chest infections occur in patients with poor oral hygiene and underlying diseases that may lead to aspiration, the identification of Trichomonas infection should be noted. Early confirmation of the diagnosis often requires mNGS and PCR. Metronidazole is essentially effective against Trichomonas, and medical thoracoscopy can be used to manage pleural conditions if necessary.

ROS-responsive resveratrol-loaded cyclodextrin nanomicelles reduce inflammatory osteolysis.

Bone loss in inflammatory disorders such as osteomyelitis, septic arthritis, and periodontitis is caused by excessive osteoclastic activity. Meanwhile, reactive oxygen species (ROS) have been identified as contributors to osteoclast differentiation, and the application of ROS scavengers has emerged as a promising strategy to protect against bone loss. Recently, resveratrol (RSV), a polyphenolic phytoalexin, has been demonstrated to inhibit osteoclastogenesis by scavenging ROS; however, the application of RSV as an antioxidant is limited by its low water solubility, structural instability, and short elimination half-life. In this study, we developed a PEGylated cyclodextrin (CD)-based nanoplatform (PCP) for local delivery of RSV as nanomicelles (RSV-NMs). In addition, polymer functionalization with phenylboronic acid ester in RSV-NMs successfully achieved ROS-responsive release of RSV. The RSV-NMs in a well-dispersed state possessed good biocompatibility as well as improved solubility and stability compared with RSV compound. In vitro, RSV-NMs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and suppressed F-actin (filamentous actin) ring formation. Additionally, the mRNA expressions of osteoclastic marker genes, including matrix metalloprotein-9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), TRAP, and cathepsin K, were consequently downregulated in the presence of RSV-NMs. In vivo, RSV-NMs provided protection against LPS-induced bone destruction, as evidenced by a decreased number of osteoclasts, increased bone density, and reduced area of bone resorption. Taken together, these results indicate that our ROS-responsive RSV-NMs can be employed as a potential therapeutic agent for the treatment of inflammatory osteolysis.

Strongyloides stercoralis hyperinfection syndrome mimicking pseudomembranous enteritis, complicated by Escherichia coli bacteremia and Pneumocystis jirovecii pneumonia in a patient after immunosuppressive therapy: a case report.

BACKGROUND: Strongyloidiasis, caused by Strongyloides stercoralis (S. stercoralis), is endemic worldwide, especially in countries with warm and humid climates. Strongyloides stercoralis hyperinfection syndrome (SHS) is an extremely serious manifestation of strongyloidiasis, which results from an acute exacerbation of auto-infection and is often fatal. CASE PRESENTATION: We present a case of SHS mimicking pseudomembranous enteritis with a final definitive diagnosis of a triple infection including S. stercoralis, Escherchia coli (E. coli) and Pneumocytis jirovecii (P. jirovecii) that occurred in a microscopic polyangiitis (MPA) patient after immunosuppressive therapy. SHS, together with E. coli bacteremia and Pneumocytis jirovecii pneumonia (PJP) in the same patient, is rare in clinical practice, which is first reported worldwide, to our knowledge. After the diagnosis was confirmed, the treatment protocol was quickly adjusted; however, the patient's life could not be saved. CONCLUSION: This case reminds us of the necessity to consider strongyloidiasis as a differential diagnosis in immunocompromised populations who live in or have visited to S. stercoralis endemic areas, especially patients with suspected pseudomembranous enteritis, even if stool examination, serological tests, and eosinophilia are negative. For this group, it is advisable to complete the relevant endoscopy and/or PCR as soon as possible. The fundamental solution to prevent this catastrophic outcome is to implement effective preventive measures at multiple levels, including physicians, patients, and relevant authorities.

THE STRUCTURE FORMAT OF ABSTRACTS: A SURVEY OF LEADING DENTAL JOURNALS AND THEIR EDITORS.

OBJECTIVES: To present the actual usage of different structure formats in abstracts of randomized controlled trials (RCTs) and systematic reviews (SRs) published in SCIE-indexed dental journals, and to assess the awareness, knowledge, as well as attitudes towards the structured formats of RCT and SR abstracts among editors-in-chief (EICs) of dental journals. METHODS: In the first part of this study, we selected SCIE-indexed dental journals and assessed their eligibility according to pre-determined criteria. All RCTs and SRs published in the included journals during January-June 2020 were identified through a hand-search. The actual usage of different structure formats and headings, as well as relevant editorial policies were extracted. In the second part, an anonymous online survey among the EICs of included dental journals was conducted. RESULTS: A total of 88 journals were included, from which 364 RCT abstracts and 130 SR abstracts were identified. For RCT abstracts, 86% were structured, with 83% in IMRaD format (Introduction, Methods, Results, and Discussion) and 3% in highly structured (HS) format. For SR abstracts, 80% were structured, including 73% in IMRaD and 7% in HS format. According to the "instructions to authors", most journals required either IMRaD (68%) or HS (5%) for RCTs, while less than half required either IMRaD (36%) or HS (9%) for SRs. Twenty-one (24%) EICs participated in our survey, among which 18 agreed that structured formats could improve the reporting quality of RCT abstracts, while only 12 of them thought HS format should be widely recommended in the dental field. CONCLUSIONS: Compared with the HS format, IMRaD was more frequently used and required among RCT and SR abstracts in dentistry. Structured formats held a relatively high degree of recognition among EICs of dental journals. Joint efforts are needed for improving the awareness and usage of HS format.

Relationship between Acute Respiratory Tract Infection and the Serum 25(OH) D3 Level in Chronic Kidney Disease Patients and Its Prevention and Treatment.

Observational studies and randomized controlled studies propose that vitamin D plays a significant role in preventing acute respiratory tract infection (RTI); however, results are inconsistent and the optimal serum 25-hydroxyvitamin D (25-OH-D3) concentration remains unknown. This study explores the risk factors associated with acute RTI in patients with chronic kidney disease (CKD) and analyzes its correlation with serum 25-OH-D3 levels, to provide appropriate preventive treatment measures for CKD patients complicated with acute RTI. Seventy cases of CKD patients treated in the department of nephrology of Jiangxi Provincial People's Hospital are recruited as the research objects and divided into a control group (CKD without RTI) and an observation group (CKD with RTI), with 35 cases in each group. The laboratory indexes and serum 25-OH-D3 levels are compared between the two groups. The area under the receiver operating characteristic curve (ROC) of 25-OH-D3 in the diagnosis of CKD patients complicated with RTI is 0.892, and the standard error is 0.038. The glomerular filtration rates (GFR) are 48.32 ± 9.87 mL/min and 50.18 ± 20.71 mL/min in the control group and the experimental group, respectively, with no statistical significance between the two groups (P > 0.05). The serum 25-OH-D3 content in the control group (35.08 ± 6.2 nmol/L) is dramatically higher than that in the observation group (20.71 ± 5.87 nmol/L) (P < 0.05). The proportion of patients with diabetes mellitus (DM) in the control group and observation group is 25.71% and 68.57%, respectively, with a considerable difference (P < 0.05). In the control group and the experimental group, the proportion of patients with oral vitamin D receptor agonists is 54.29% and 11.43%, respectively, and the difference is significant (P < 0.05). Results show that the serum 25-OH-D3 level is highly correlated with the occurrence of RTI in CKD patients. In addition, it is related to patients' age, DM, and vitamin D receptor agonists.

Sustained release of chlorogenic acid-loaded nanomicelles alleviates bone loss in mouse periodontitis.

Periodontitis is a prevalent chronic inflammatory disease that destroys the periodontal supporting tissues, impinges on oral health, and is correlated with an increased risk of systemic disease. Currently, the main drug treatment is antibiotic therapy; however, systemic antibiotic therapy still has various drawbacks such as bacterial resistance, low bioavailability and burst release. It is noteworthy that the local use of non-antibiotic drugs with sustained release characteristics can effectively overcome these problems. It has been documented that chlorogenic acid (CGA) has good anti-inflammatory and antioxidant properties. To achieve the sustained release of CGA, we synthesized CGA-PLGA@PVP nanomicelles by loading CGA onto poly(D,L-lactide-co-glycolide) (PLGA) and modified them with polyvinylpyrrolidone (PVP) for better dispersion. The results demonstrated that CGA-PLGA@PVP nanomicelles could prolong the release time of CGA, and could not only effectively remove reactive oxygen species (ROS) but also downregulate the overexpression of proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW264.7 cells. Moreover, CGA-PLGA@PVP nanomicelles could remain in gingival tissue for more than 24 hours after local injection, inhibit alveolar bone resorption and prevent the progression of periodontitis in a mouse model, showing good biocompatibility. Therefore, CGA-PLGA@PVP nanomicelles have great properties and are expected to be a novel therapeutic strategy for periodontitis.

Portulaca Oleracea-associated oxalate nephropathy complicated with an ANCA-positive acute renal injury: A case report.

Oxalate nephropathy is a rare disease that can lead to acute kidney injury (AKI). In clinical practice, as renal biopsy is required for diagnosis, physicians often do not have sufficient understanding of this disease. When AKI is associated with positive blood anti-neutrophil cytoplasmic antibodies (ANCA), a diagnosis of renal injury due to ANCA-associated vasculitis is likely to be made, leading to treatment with immunosuppressive therapy. A case of AKI after eating a large quantity of Portulaca oleracea is reported. While blood P-ANCA was positive, both urine proteinuria and urine occult blood were negative. Renal biopsy was performed and identified an acute tubulointerstitial injury: disc-shaped crystals were seen in the lumen of renal tubules that demonstrated birefringence under polarized light, and an oxalate nephropathy was therefore diagnosed. Typical histological changes of an ANCA-associated vasculitis with renal injury such as cellulose-like necrosis and crescent formation were not present. After the patient stopped eating P. oleracea, and following rehydration and hemodialysis, renal function returned to normal. In patients with AKI, the secondary causes of hyperoxalemia should be sought and attention paid to excluding an oxalate nephropathy. In patients with AKI who are ANCA-positive, it is prudent to complete the renal pathological diagnostic process before assuming that the renal injury is caused by an ANCA-associated vasculitis, and before starting hormone and immunosuppressive therapy.

Ginkgo biloba Extract Attenuates the Disruption of Pro- and Anti-inflammatory Balance of Peripheral Blood in Arsenism Patients by Decreasing Hypermethylation of the Foxp3 Promoter Region.

Coal-burning type of arsenism, a chronic arsenism caused by environmental arsenic pollution, found firstly at Guizhou Province of China, manifested as the disruption of pro- and anti-inflammatory T cell balance and multiple organ damage, while no specific treatment for the arsenism patients. The effect of methylation of the forkhead box P3 (Foxp3) promoter region on arsenic-induced disruption of pro- and anti-inflammatory T cell balance was first evaluated in this study, between the control and arsenism groups. The results show that arsenic can induce the hypermethylation of 6 sites in the Foxp3 promoter by upregulating the expression of recombinant DNA Methyltransferase 1 (Dnmt1) mRNA, leading to the downregulation of Foxp3 mRNA, Tregs, and interleukin 10 (IL-10, anti-inflammatory cytokine) levels, and increased the levels of interleukin 17 (IL-17, pro-inflammatory cytokine) in the peripheral blood of patients with arsenic poisoning. Further randomized controlled double-blind experiments (including the placebo control groups and the Ginkgo biloba extract (GBE) intervention groups) showed that compared to the placebo control group or before GBE intervention, the levels of Dnmt1 mRNA, Foxp3 methylation, and IL-17 in the peripheral blood of the GBE intervention group were significantly decreased after intervention (P < 0.05), but the levels of regulatory T cells (Tregs) and IL-10 were significantly increased (P < 0.05). Our study provides some limited evidence that GBE can attenuate the disruption of pro- and anti-inflammatory balance of peripheral blood in arsenism patients by decreasing hypermethylation of the Foxp3 promoter region. This study provides scientific basis for further understanding a possible natural medicinal plant, GBE, as a more effective measure to prevent and control the disruption of pro- and anti-inflammatory balance caused by coal-burning type of arsenism.

circCDYL2 promotes trastuzumab resistance via sustaining HER2 downstream signaling in breast cancer.

BACKGROUND: Approximate 25% HER2-positive (HER2+) breast cancer (BC) patients treated with trastuzumab recurred rapidly. However, the mechanisms underlying trastuzumab resistance remained largely unclear. METHODS: Trastuzumab-resistant associated circRNAs were identified by circRNAs high-throughput screen and qRT-PCR in HER2+ breast cancer tissues with different trastuzumab response. The biological roles of trastuzumab-resistant associated circRNAs were detected by cell vitality assay, colony formation assay, Edu assay, patient-derived xenograft (PDX) models and orthotopic animal models. For mechanisms research, the co-immunoprecipitation, Western blot, immunofluorescence, and pull down assays confirmed the relevant mechanisms of circRNA and binding proteins. RESULTS: We identified a circRNA circCDYL2, which was overexpressed in trastuzumab-resistant patients, which conferred trastuzumab resistance in breast cancer cells in vitro and in vivo. Mechanically, circCDYL2 stabilized GRB7 by preventing its ubiquitination degradation and enhanced its interaction with FAK, which thus sustained the activities of downstream AKT and ERK1/2. Trastuzumab-resistance of HER2+ BC cells with high circCDYL2 could be reversed by FAK or GRB7 inhibitor. Clinically, HER2+ BC patients with high levels of circCDYL2 developed rapid recurrence and had shorter disease-free survival (DFS) and overall survival (OS) following anti-HER2 therapy compared to those with low circCDYL2. CONCLUSIONS: circCDYL2-GRB7-FAK complex plays a critical role in maintaining HER2 signaling, which contributes to trastuzumab resistance and circCDYL2 is a potential biomarker for trastuzumab-resistance in HER2+ BC patients.