Development and validation of a major adverse limb events prediction model for peripheral arterial disease with frailty.

OBJECTIVE: To investigate the risk factors for major limb adverse events (MALE) in peripheral arterial disease (PAD) combined with frailty and to develop and validate a risk prediction model of MALE. METHODS: This prospective study was performed in the vascular surgery department of patients in six hospitals in southwest China. Prospective collection of patients with PAD combined with frailty from February 1 to December 20, 2021, with MALE as the primary outcome, and followed for 1 year. The cohort was divided into a development cohort and a validation cohort. In the development cohort, a multivariate risk prediction model was developed to predict MALE using random forests for variable selection and multivariable Cox regression analysis. The model is represented by a visualized nomogram and a web-based calculator. The model performance was tested with the validation cohort and assessed using the C-statistic and calibration plots. RESULTS: A total of 1179 patients were prospectively enrolled from February 1 to December 20, 2021. Among 816 patients with PAD who were included in the analysis, the median follow-up period for this study was 9 ± 4.07 months, the mean age was 74.64 ± 9.43 years, and 249 (30.5%) were women. Within 1 year, 222 patients (27.2%) developed MALE. Target lesion revascularizations were performed in 99 patients (12.1%), and amputations were performed in 131 patients (16.1%). The mortality rate within the whole cohort was 108 patients (13.2%). After controlling for competing risk events (death), the cumulative risk of developing MALE was not statistically different. Prealbumin (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.41-0.89; P = .010), percutaneous coronary intervention (HR, 2.31; 95% CI, 1.26-4.21; P = .006), Rutherford classification (HR, 1.77; 95% CI, 1.36-2.31; P < .001), white blood cell (HR, 1.85; 95% CI, 1.20-2.87; P = .005), high altitude area (HR, 3.1; 95% CI, 1.43-6.75; P = .004), endovascular treatment (HR, 10.2; 95% CI, 1.44-72.50; P = .020), and length of stay (HR, 1.01; 95% CI, 1.00-1.03; P = .012) were risk factors for MALE. The MALE prediction model had a C-statistic of 0.76 (95% CI, 0.70-0.79). The C-statistic was 0.68 for internal validation and 0.66 for external validation for the MALE prediction model. The MALE prediction model for PAD presented an interactive nomogram and a web-based network calculator. CONCLUSIONS: In this study, the MALE prediction model has a discriminative ability to predict MALE among patients with PAD in frailty. The MALE model can optimize clinical decision-making for patients with PAD in frailty.

Application of Lipid Apheresis in Acute Lipogenic Pancreatitis.

INTRODUCTION: Recently, the incidence of hypertriglyceridemia-associated pancreatitis (HTG-AP) has been increasing. The pathogenesis of lipogenic pancreatitis is not fully understood. This study aimed to retrospectively analyze the laboratory data, clinical manifestations, and prognosis of patients with lipid-derived pancreatitis who received lipid purification, to explore whether lipid purification is a better treatment for acute hyperlipidemic pancreatitis. METHODS: In this study, we enrolled five subjects diagnosed with HTG-AP at the Second Xiangya Hospital of Central South University between 2021 and 2022. We collected demographic data, medical histories, clinical manifestations, and laboratory data. All patients received routine therapy. Blood lipid purification was conducted using the double filtration plasmapheresis (DFPP) method. Plasma was separated from blood cells and purified to remove cholesterol, triglycerides, and low-density lipoprotein (LDL). SPSS was used for statistical analyses. RESULTS: Following a single lipoprotein apheresis (LA) treatment, significant improvements in serum lipid levels were observed. Three patients achieved triglyceride levels below 5.65 mmol/L within 24 h, while the remaining 2 patients experienced reductions of 82% and 78%, respectively. The average triglyceride level decreased from 36.82 to 7.27 mmol/L, representing an 80% reduction from baseline. Total cholesterol decreased by 59% on average, and LDL levels decreased by 69%. Statistically significant differences were observed in triglyceride and cholesterol levels before and after treatment. Four patients exhibited increased HDL levels posttreatment, while 1 patient showed a decrease. The average HDL/TC level was 21% higher after treatment. CONCLUSION: LA in HTG-AP effectively improves clinical symptoms, rapidly lowers lipid levels, and achieves good therapeutic outcomes.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer.

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011-2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Household air pollution and urinary incontinence symptoms among older adults in LASI: a large-scale population-based study.

BACKGROUND: The effects of household air pollution on urinary incontinence (UI) symptoms and stress urinary incontinence (SUI) symptoms have not been studied. This study seeks to investigate the correlation between household air pollution and UI/SUI symptoms among middle-aged and elderly adults in India. METHODS: We employed data derived from individuals aged 45 years and older who participated in the inaugural wave (2017-2018) of the Longitudinal Aging Study in India (LASI). The assessment of household air pollution exposure and the occurrence of UI/SUI symptoms relied on self-reported data. The analytical approach adopted was cross-sectional in nature and encompassed a cohort of 64,398 participants. To explore relationships, we utilized multivariate logistic regression analysis, incorporating subgroup analysis and interaction tests. RESULTS: 1,671 (2.59%) participants reported UI symptoms and 4,862 (7.55%) participants reported SUI symptoms. Also, the prevalence of UI/SUI symptoms is much higher among middle-aged and elderly adults who use solid polluting fuels (UI: 51.23% vs. 48.77%; SUI: 54.50% vs. 45.50%). The results revealed a noteworthy correlation between household air pollution and the probability of experiencing UI/SUI symptoms, persisting even after adjusting for all conceivable confounding variables (UI: OR = 1.552, 95% CI: 1.377-1.749, p < 0.00001; SUI: OR: 1.459, 95% CI: 1.357-1.568, p < 0.00001). Moreover, significant interaction effects were discerned for age, education level, tobacco consumption, alcohol consumption, and physical activity (p for interaction < 0.05). CONCLUSIONS: The results of our study indicate that the utilization of solid fuels in the home increases the likelihood of developing urinary incontinence and stress urinary incontinence. As a result, we argue that there is an immediate need to reform the composition of cooking fuel and raise public awareness about the adverse effects of air pollution in the home.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Di-(2-ethylhexyl) phthalate promotes benign prostatic hyperplasia through KIF11-Wnt/ß-catenin signaling pathway.

Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3ß and elevate the levels of ß-catenin, thereby activating the Wnt/ß-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/ß-catenin signaling pathway.

ABRO1 promotes NLRP3 inflammasome activation through regulation of NLRP3 deubiquitination.

Deubiquitination of NLRP3 has been suggested to contribute to inflammasome activation, but the roles and molecular mechanisms are still unclear. We here demonstrate that ABRO1, a subunit of the BRISC deubiquitinase complex, is necessary for optimal NLRP3-ASC complex formation, ASC oligomerization, caspase-1 activation, and IL-1ß and IL-18 production upon treatment with NLRP3 ligands after the priming step, indicating that efficient NLRP3 activation requires ABRO1. Moreover, we report that ABRO1 deficiency results in a remarkable attenuation in the syndrome severity of NLRP3-associated inflammatory diseases, including MSU- and Alum-induced peritonitis and LPS-induced sepsis in mice. Mechanistic studies reveal that LPS priming induces ABRO1 binding to NLRP3 in an S194 phosphorylation-dependent manner, subsequently recruiting the BRISC to remove K63-linked ubiquitin chains of NLRP3 upon stimulation with activators. Furthermore, deficiency of BRCC3, the catalytically active component of BRISC, displays similar phenotypes to ABRO1 knockout mice. Our findings reveal an ABRO1-mediated regulatory signaling system that controls activation of the NLRP3 inflammasome and provide novel potential targets for treating NLRP3-associated inflammatory diseases.

Comparative analysis of the chrysanthemum transcriptome with DNA methylation inhibitors treatment and silencing MET1 lines.

BACKGROUND: As one of the ten most famous flowers in China, the chrysanthemum has rich germplasm with a variety of flowering induction pathways, most of which are photoperiod-induced. After treatment with DNA methylation inhibitors, it was found that DNA methylation plays an important role in flowering regulation, but the mechanism of action remains unclear. Therefore, in this study, curcumin, 5-azaC, their mixed treatment, and MET1-RNAi lines were used for transcriptome sequencing to find out how different treatments affected gene expression in chrysanthemums at different stages of flowering. RESULTS: Genomic DNA methylation levels were measured using HPLC technology. The methylation level of the whole genome in the vegetative growth stage was higher than that in the flowering stage. The methylation level of DNA in the vegetative growth stage was the lowest in the curcumin and mixed treatment, and the methylation level of DNA in the transgenic line, mixed treatment, and curcumin treatment was the lowest in the flowering stage. The flowering rate of mixed treatment and curcumin treatment was the lowest. Analysis of differentially expressed genes in transcriptomes showed that 5-azaC treatment had the most differentially expressed genes, followed by curcumin and transgenic lines, and mixed treatment had the fewest. In addition, 5-azaC treatment resulted in the differential expression of multiple DNA methylation transferases, which led to the differential expression of many genes. Analysis of differentially expressed genes in different treatments revealed that different treatments had gene specificity. However, the down-regulated GO pathway in all 4 treatments was involved in the negative regulation of the reproductive process, and post-embryonic development, and regulation of flower development. Several genes associated with DNA methylation and flowering regulation showed differential expression in response to various treatments. CONCLUSIONS: Both DNA methylase reagent treatment and targeted silencing of the MET1 gene can cause differential expression of the genes. The operation of the exogenous application is simple, but the affected genes are exceedingly diverse and untargeted. Therefore, it is possible to construct populations with DNA methylation phenotypic diversity and to screen genes for DNA methylation regulation.

Effects of Curcumin on Axon Growth and Myelin Sheath Formation in an In Vitro Model.

Although the beneficial effects of curcumin, extracted from rhizomes of the ginger family genus Curcuma, on the repair and regeneration of nerves have been evaluated in vitro, there are few studies concerning its effects on axon myelination. Here, we used pheochromocytoma cells as an in vitro model of peripheral nerves. Pheochromocytoma cells were cultured alone or cocultured with Schwann cells and treated with increasing concentrations of curcumin. Cell growth was observed, and the expression levels of growth-associated protein 43 (GAP-43), microtubule-associated protein 2 (MAP-2), myelin basic protein (MBP), myelin protein zero (MPZ), Krox-20, and octamer binding factor 6 (Oct-6) were quantified. We found a significant increase in expression of all six proteins following curcumin treatment, with a corresponding increase in the levels of MBP, MPZ, Krox-20, and Oct-6 mRNA. Upregulation was greater with increasing curcumin concentration, showing a concentration-dependent effect. The results suggested that curcumin can promote the growth of axons by upregulating the expression of GAP-43 and MAP-2, stimulate synthesis and secretion of myelin-related proteins, and facilitate formation of the myelin sheath in axons by upregulating the expression of Krox-20 and Oct-6. Therefore, curcumin could be widely applied in future strategies for the treatment of nerve injuries.

The relationship between depression and benign prostatic hyperplasia in middle-aged and elderly men in India: a large-scale population study.

BACKGROUND: There have been few investigations on the association between depression and benign prostatic hyperplasia (BPH). This study aims to explore the correlation between depression and BPH among middle-aged and older men in India. METHODS: We utilized data from male individuals aged 45 years and older who participated in the initial wave (2017-2018) of the Longitudinal Aging Study in India (LASI). The presence of BPH symptoms was based on self-reported information, while depressive symptoms were evaluated using CESD-10. The analysis was a cross-sectional study conducted on a final sample size of 30,108 male participants. To examine associations, we employed multivariate logistic regression analysis along with subgroup analysis and interaction tests. RESULTS: A total of 439 (1.46%) men reported BPH and had a higher depression score (10.18 ± 4.22 vs. 9.28 ± 4.00). The findings indicated a significant association between the depression score and the likelihood of developing BPH, even after accounting for all potential confounding variables (OR = 1.054, 95% CI: 1.030-1.078, p < 0.00001). The participants were then categorized into a depression group and a normal group based on their CESD-10 score, using a threshold of 10 to ascertain the existence or nonexistence of depression. After adjusting for all variables in model IV, the findings continued to exhibit statistical significance (OR = 1.611, CI: 1.327-1.955, p < 0.00001). Significant interaction effects of age, education level, caste or tribe, and alcohol consumption were observed (p for interaction < 0.05). CONCLUSION: Our research found that BPH was significantly linked to the presence of depressive symptoms among middle-aged and elderly Indian men. Additional prospective research is necessary to clarify this association and investigate potential mechanisms.

The Controlling Nutritional Status (CONUT) Score and Prognosis in Malignant Tumors: A Systematic Review and Meta-Analysis.

Increasing evidences indicate that the controlling nutritional status (CONUT) score is associated with cancer prognosis. This study was conducted to investigate the prognostic significance of pretreatment CONUT score on patients with various malignant tumors. The correlation between CONUT score and clinical outcomes of tumor patients were studied by electronic literature retrieval. Pooled hazard ratios (HR), odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to clarify the conclusion. Subgroup analysis were conducted in line with cancer type, cancer stage, treatment, sample size and cut-off value. A total of 62 studies involving 25224 patients were included in this study. Pooled analysis showed that higher CONUT scores were associated with shorter overall survival (HR 1.62, 95% CI 1.45-1.79, p < 0.001), cancer-specific survival (HR 1.80, 95% CI 1.48-2.13, p < 0.001), progress/recurrence-free survival (HR 1.54, 95% CI 1.23-1.85, p < 0.001) and disease-free survival (HR 1.56, 95% CI 1.39-1.74, p < 0.001). In addition, high CONUT score was correlated to higher incidence of postoperative complications (OR 1.64, 95% CI 1.38-1.95, p < 0.001) and mortality (OR 4.22, 95% CI 2.22-8.02, p < 0.001). Consequently, the pretreatment CONUT score is a valuable indicator to predict the clinical outcomes of patients with various malignant tumors.

Second Malignant Tumors and Non-Tumor Causes of Death for Patients With Penile Cancer During Their Survivorship.

BACKGROUND: The aim was to evaluate the causes of death for patients with localized, regional and metastatic penile cancer (PeCa) after diagnosis. METHODS: PeCa patients diagnosed during 2004-2018 in the Surveillance, Epidemiology, and End Results program database were identified. Causes of deaths including PeCa, second malignant tumors (SMTs) and non-tumor diseases were analyzed, as well as the standardized mortality ratio (SMR) of each cause. RESULTS: For localized PeCa, 800 of 2155 patients died during the follow-up. 24.9% of all deaths were due to PeCa. 18.0% and 57.1% deaths were due to SMTs and non-tumor causes. Main SMTs included cancers of lung and bronchus (n = 40) and skin (n = 11) with significantly increased SMRs of 1.71 (1.22-2.33) and 4.82 (2.41-8.63). Mortality risks of other SMTs were mostly similar with the general populations. Main causes of non-tumor diseases included diseases of heart [n = 172, SMR: 1.66 (1.42-1.93)], COPD and allied cond [n = 38, SMR: 1.63 (1.15-2.24)], and cerebrovascular diseases [n = 33, SMR: 1.71 (1.17-2.4)]. For regional PeCa, 679 of 1310 patients died including 43.5% PeCa, 14.8% SMTs and 26.6% non-tumor causes. The mortality risks of cancers from lung and bronchus [SMR: 2.41 (1.53-3.62)], skin [SMR: 6.41 (2.35-13.95)] and testis [SMR: 149.35 (18.09-539.5)] were significantly increased. Main non-tumor causes of death included diseases of heart [n = 71, SMR: 1.77 (1.38-2.23)], COPD and allied cond [n = 17, SMR: 1.85 (1.08-2.95)] and diabetes mellitus [n = 16, SMR: 3.62 (2.07-5.88)]. For distant diseases, 109 of 132 patients died including 76 (69.7%) died for PeCa itself, 24 (22.0%) died for SMTs and 9 (8.3%) died for non-tumor diseases. The majority of PeCa deaths (67.1%) and SMTs deaths (79.2%) occurred within 1 year after the diagnosis of PeCa. CONCLUSIONS: We firstly analyzed the SMTs and non-tumor causes of death and morality risks of each cause for PeCa patients, which provided valuable information for PeCa patients on disease prevention and health care during their survivorship.

The prognostic value of the Controlling Nutritional Status score on patients undergoing nephrectomy for upper tract urothelial carcinoma or renal cell carcinoma: a systematic review and meta-analysis.

In recent years, the controlling nutritional status (CONUT) score has increasingly became an effective indicator associated with tumor prognosis. This study was conducted to synthesise data on the prognostic value of CONUT score on patients with upper tract urothelial carcinoma (UTUC) or renal cell carcinoma (RCC) undergoing nephrectomy. We designed and performed a systematic analysis of studies that verified the correlation between preoperative CONUT score and prognosis for UTUC and RCC using PubMed, Web of Science and Embase. The conclusion was clarified by pooled hazard ratios (HR) and 95% confidence intervals (95% CI). Subgroup analysis were further conducted in accordance with different primary tumor. Six studies involving 3529 patients were included in this evidence synthesis, which revealed that the CONUT score had a potential role to predict the survival of UTUC and RCC patients accepting surgery. Pooled analysis showed that the overall survival (OS, HR 2·32, p < 0·0001), cancer-specific survival (CSS, HR 2·68, p < 0·0001) and disease-free survival (DFS, HR 1·62, p < 0·00001) were inferior in the high CONUT score group when compared with low score group. Subgroup analysis revealed that this result was in line with UTUC (OS: HR 1·86, p = 0·02; CSS: HR 2·24, p = 0·01; DFS: HR 1·54, p < 0·00001) and RCC (OS: HR 3·05, p < 0·00001; CSS: HR 3·47, p < 0·00001; DFS: HR 2·21, p = 0·0005) patients respectively. Consequently, the CONUT score is a valuable preoperative index to predict the survival of patients with UTUC or RCC undergoing nephrectomy.

The Prognosis of Radical Prostatectomy, External Beam Radiotherapy plus Brachytherapy, and External Beam Radiotherapy Alone for Patients above 70 Years with Very High-Risk Prostate Cancer: A Population-Matched Study.

OBJECTIVE: The aim of this study was to evaluate the survival outcomes of radical prostatectomy (RP), external beam radiotherapy plus brachytherapy (EBRT + BT), and EBRT alone among elderly men (aged 70 years and above) with very high-risk (VHR) prostate cancer (PCa). METHODS: We identified elderly men diagnosed with VHR PCa between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database. The propensity score-matching method was adopted to balance the covariates and generate new cohorts. -Kaplan-Meier and Cox analyses were conducted to build up survival curves and evaluate the overall survival (OS) and PCa-specific survival (PCSS) outcomes. RESULTS: A total of 9,818 patients were identified. Of them, 5,839 were in the EBRT group, 725 in the EBRT + BT group, and 3,254 in the RP group. The survival curves of the overall cohort showed that RP was associated with the best OS, followed by EBRT + BT and EBRT (p < 0.001). As for the PCSS, RP shared similar outcomes with EBRT + BT (hazard ratio [HR]: 1.25 [0.93-1.69], p = 0.175). EBRT was associated with significantly worse PCSS than both RP (HR: 1.88, 95% confidence interval [95% CI] [1.64-2.15], p < 0.001) and EBRT + BT (HR: 1.48, 95% CI [1.19-1.85], p = 0.002). In the matched cohorts, RP presented better OS (HR: 1.41, 95% CI [1.07-1.86], p = 0.041) and similar PCSS with EBRT + BT (HR: 1.50, 95% CI [0.91-2.47], p = 0.12). RP was associated with significantly better OS and PCSS outcomes than EBRT alone (OS HR: 1.58, 95% CI [1.59-2.12], p < 0.001; PCSS HR: 2.08 [1.60-2.72], p < 0.001). EBRT + BT also had significantly better OS and PCSS outcomes than EBRT alone (OS HR: 1.33, 95% CI [1.11-1.60], p < 0.001; PCSS HR: 1.57 [1.13-2.19], p = 0.003). CONCLUSIONS: For patients above 70 years with VHR PCa, RP was associated with better OS and similar PCSS than EBRT + BT. Both RP and EBRT + BT have better OS and PCSS than EBRT alone.

First report of a new bacterial stem rot disease of strawberry (Fragaria×ananassa) caused by Pantoea ananatis in Jiangsu, China.

Strawberry (Fragaria×ananassa Duch.) is an important economic fruit crop in the world. With the continuous expansion of strawberry planting area, strawberry disease is one of the most important limiting factors, which seriously affects the agronomic performance and leads to significant economic losses. In November 2020, an infected stem rot disease of strawberries was detected in the strawberry growing area of Donghai County, Jiangsu Province, China. The disease incidence ranged from 30 % to 45 %. Initially, infected plants included stunted growth of new leaves, leaflet asymmetry, and holes in the vertical section of the stem, resulting in leaf blight and death in severe cases. To isolate the pathogen, two symptomatic plants were randomly collected. And then infected plants were surface sterilized with 75 % ethanol for 1 min, followed by 2 % sodium hypochlorite for 6 minutes. After that, the infected plants were washed 4-5 times with double sterilized distilled water, cut into 3-5 mm small pieces, and soaked in 2 ml of sterile water for 15 min, after which 100 µl of liquid suspension were spread onto Luria-Bertani medium (LB) and incubated at 28 °C for 12-16 h. All isolates showed yellow, viscous, round, and smooth (Figure S1, C) and the isolates were designated as JX1 and JX2. To identify the pathogen, the genomic DNA were extracted from isolates using the Ezup Column Bacteria Genomic DNA Purification Kit (Sangon Biotech, China) and the fragments of gyrB, rpoB and leuS gene were amplified using the primer pairs UP-1S/UP-2Sr (Yamamoto and Harayama 1995), rpoB-F/rpoB-R and leuS-F/leuS-R (Yu et al. 2022), respectively. Sequence analyses showed that the nucleotide sequences of gyrB, rpoB, and leuS fragments of the isolates shared 99.72 %, 99.67 % and 98.37 % identity with the Pantoea ananatis type strain LMG 2665 (KF482590.1, EF988972.1 and KF482626.1, respectively ), which suggests that the isolate could be Pantoea ananatis. To further verify that P. ananatis was identity of these isolates, the whole genome was sequenced using PacBio sequel II technology. The Average Nucleotide Identity (ANI) calculation showed that the whole-genome sequence was 99.0% similar to that of the Pantoea ananatis type strain LMG 2665 (Jain et al. 2018). The isolates were therefore recognized as P. ananatis. To confirm pathogenicity, roots of strawberry plants were inoculated by wounding as described (Wang et al. 2017) with bacterial suspensions (108 CFU/ml) for 30 min, and transplanted into 10 cm ×8.5 cm pots filled with substrate (peat: perlite: vermiculite =3:1:1). The negative control plants were inoculated with sterile distilled water (20 individual plants per group). All infected plants were placed in a greenhouse under the following environmental conditions: 30 ℃/25 ℃ day/night, >70 % relative humidity, 16-h/8-h photoperiod. The experiment was carried out three times. After 3 to 4 weeks of inoculation, the new leaves of the plants were smaller and asymmetrical, while the negative plants remained healthy. After 8 weeks, a significant stem rot pocket developed on all inoculated plants, similar to the symptoms observed in the field. In contrast, no symptoms were observed in negative plants (Figure S2). To fulfill Koch's postulates bacteria were further isolated, purified and identified from the greenhouse inoculated plants. The results proved that the causative agent of strawberry stem rot was P. ananatis. In recent decades, P. ananatis has been found to cause bacterial leaf blight in strawberries (Bajpai et al. 2020). It has also caused other crop diseases, such as maize white spot, peach soft rot and others (Cui et al.2022; Liao et al. 2015). Although other crop diseases caused by P. ananatis, a bacterial pathogen, there has been no report of P. ananatis causing the symptoms of stem rot disease in strawberry. To our knowledge, this is the first report of P. ananatis causing stem rot in strawberry. This study provides solid evidence that strawberry stem rot disease in China can also be caused by the novel pathogen Pantoea ananatis. In conclusion, this report will provide a theoretical reference for the prevention and control measures of P. ananatis causing strawberry stem rot disease in the future.

Oxalate crystal-related acute renal injury caused by orlistat: A case report. / å¥¥åˆ©å¸ä»–è‡´è‰é ¸ç›ç»“æ™¶ç›¸å ³æ€¥æ€§è‚¾æŸä¼¤1例.

We reported a case of oxalate crystal-related acute kidney injury caused by orlistat. The patient was admitted for nephrotic syndrome and acute kidney injury. The pathomorphological assessment of renal biopsy showed intratubular oxalate crystals. The patient reported that she had taken orlistat regularly to loss weight for more than a year. This patient had a habit of drinking vegetable soup and strong herbal tea daily. Orlistat, an intestinal lipase inhibitor, may cause secondary hyperoxaluria, that is, intestinal hyperoxaluria. Dietary habits could be a common precipitating factor for orlistat-relevant hyperoxaluria. It was comprehensively considered to be oxalate crystal-related acute renal injury, and the patient's renal function recovered gradually after drug withdrawal. Clinicians should pay attention to screening drug-related acute kidney injury including orlistat when observing patients with unexplained acute kidney injury, and renal biopsy should be performed if necessary. It is also important to warn people who take the orlistat for weight loss about the side effects of this drug so as to adjust the eating habits.

Transcriptional regulation of human abraxas brother protein 1 expression by yin yang 1.

Abraxas brother protein 1 (ABRO1) is a subunit of the deubiquitinating enzyme BRCC36-containing isopeptidase complex and plays important roles in cellular responses to stress by interacting with its binding partners, such as ubiquitin-specific peptidase 7, p53, activating transcription factor 4, THAP-domain containing 5, and serine hydroxymethyltransferase. However, the transcriptional regulation of ABRO1 remains unexplored. In this study, we identified and characterized the core regulatory elements of the human ABRO1 gene and mapped them to the ABRO1 promoter region. Additionally, 5' rapid amplification of cDNA ends revealed that the transcriptional start site (TSS) was located -13 bp upstream from the start codon. Reporter gene, chromatin immunoprecipitation, and electrophoretic mobility shift assays demonstrated that ABRO1 transcription was regulated through cis-acting elements located in the region -89 to -59 bp upstream of the ABRO1 TSS and that these elements were targeted by yin yang 1 transcription factor (YY1). Moreover, YY1 overexpression increased human ABRO1 mRNA and protein expression, and small-interfering RNA-mediated downregulation of YY1 attenuated ABRO1 expression. These results suggested that YY1 positively regulated human ABRO1 expression by binding to cis-acting elements located in the ABRO1 TSS.

Identification of key genes for HNSCC from public databases using bioinformatics analysis.

BACKGROUND: The cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear. Our study aims to identify the key genes associated with HNSCC and reveal potential biomarkers. METHODS: In this study, the expression profile dataset GSE83519 of the Gene Expression Omnibus database and the RNA sequencing dataset of HNSCC of The Cancer Genome Atlas were included for analysis. Sixteen differentially expressed genes were screened from these two datasets using R software. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was then adopted for survival analysis, and finally, three key genes related to the overall survival of HNSCC patients were identified. Furthermore, we verified these three genes using the Oncomine database and from real-time PCR and immunohistochemistry results from HNSCC tissues. RESULTS: The expression data of 44 samples from GSE83519 and 545 samples from TCGA-HNSC were collected. Using bioinformatics, the two databases were integrated, and 16 DEGs were screened out. Gene Ontology (GO) enrichment analysis showed that the biological functions of DEGs focused primarily on the apical plasma membrane and regulation of anoikis. Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathway analysis showed that these DEGs were mainly involved in drug metabolism-cytochrome P450 and serotonergic synapses. Survival analysis identified three key genes, CEACAM5, CEACAM6 and CLCA4, that were closely related to HNSCC prognosis. The Oncomine database, qRT-PCR and IHC verified that all 3 key genes were downregulated in most HNSCC tissues compared to adjacent normal tissues. CONCLUSIONS: This study indicates that integrated bioinformatics analyses play an important role in screening for differentially expressed genes and pathways in HNSCC, helping us better understand the biomarkers and molecular mechanism of HNSCC.

Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agents in the management of paediatric monosymptomatic nocturnal enuresis: a network meta-analysis.

OBJECTIVE: To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta-analysis. MATERIALS AND METHODS: We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. RESULTS: Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate. CONCLUSIONS: The network meta-analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high-quality studies are needed for further evaluation of these treatments.

Comparison of different prognostic models for predicting cancer-specific survival in bladder transitional cell carcinoma.

OBJECTIVE: To construct the newly valuable nomogram which can compare the predictive performance with American Joint Committee on Cancer (AJCC) staging system in bladder transitional cell carcinoma (BTCC). METHODS: BTCC patients were screened (2004-2015) from the SEER database. The nomogram incorporating lymph node ratio was constructed to evaluate individualized cancer-specific survival. RESULTS: The C-index of the nomogram for predicting cancer-specific survival was 0.743 (95% CI: 0.720-0.766), which was higher than C-index of the AJCC staging system. CONCLUSION: Lymph node ratio can be a reliable prognostic indicator for BTCC. The proposed nomogram showed more satisfactory predictive accuracy and wider applicability than current AJCC staging system in individualized prediction of BTCC patients.