KAT8 enhances the resistance of lung cancer cells to cisplatin by acetylation of PKM2.

Cisplatin (CDDP)-based chemotherapy resistance is a major challenge for lung cancer treatment. PKM2 is the rate-limiting enzyme of glycolysis, which is associated with CDDP resistance. KAT8 is an acetyltransferase that regulates lung cancer progression. Thus, we aimed to explore whether KAT8 regulates PKM2 acetylation to participate in CDDP resistance. CDDP resistance was analyzed by CCK-8, flow cytometry and western blotting. To explore the regulation of KAT8 on PKM2, coimmunoprecipitation (Co-IP), immunofluorescence and immunoprecipitation followed by western blotting were performed. Glycolysis was determined using glucose consumption, lactate production, ATP level detection kits and extracellular acidification rate assay. We observed that KAT8 levels were downregulated in CDDP-treated A549 and PC9 cells. Interference with KAT8 inhibited cell viability, promoted apoptosis and upregulated PARP1 and cleaved-PARP1 levels of A549 cells treated with CDDP, suggesting the sensitivity to CDDP was enhanced, while KAT8 overexpression attenuated the CDDP sensitivity. Moreover, KAT8 interacted with PKM2 to promote the PKM2 K433 acetylation. PKM2 K433 mutated plasmids inhibited the si-KAT8-regulated cell viability, apoptosis and glycolysis compared with PKM2-WT. Besides, KAT8 reversed the inhibition of tumor growth caused by CDDP. In conclusion, KAT8-mediated PKM2 K433 acetylation was associated with the resistance of lung cancer cells to CDDP. The findings may provide a new idea for the treatment of CDDP-resistant lung cancer.

Overexpression of miR-204-5p Alleviates Osteogenic Differentiation and Calcification of Human Aortic Vascular Smooth Muscle Cells by Targeting Calcium/Calmodulin-dependent Protein Kinase 1.

ABSTRACT: Vascular calcification (VC), a major complication in chronic kidney disease (CKD), is predominantly driven by osteoblastic differentiation. Recent studies have highlighted the crucial role of microRNAs in CKD's pathogenesis. Here, our research focused on the effects of miR-204-5p and its molecular mechanisms within VC. We initially found a notable decrease in miR-204-5p levels in human aortic vascular smooth muscle cells stimulated with inorganic phosphate, using this as a VC model in vitro. Following the overexpression of miR-204-5p, a decrease in VC was observed, as indicated by alizarin red S staining and measurements of calcium content. This decrease was accompanied by lower levels of the osteogenic marker, runt-related transcription factor 2, and higher levels of α-smooth muscle actin, a marker of contractility. Further investigation showed that calcium/calmodulin-dependent protein kinase 1 (CAMK1), which is a predicted target of miR-204-5p, promotes VC. Conversely, overexpressing miR-204-5p reduced VC by suppressing CAMK1 activity. Overexpressing miR-204-5p also effectively mitigated aortic calcification in an in vivo rat model. In summary, our research indicated that targeting the miR-204-5p/CAMK1 pathway could be a viable strategy for mitigating VC in CKD patients.

Blocking miR396 activity by overexpression MIM396 improved switchgrass tiller number and biomass yield.

BACKGROUND: MicroRNA396 (miR396) plays an important role in the regulation of plant growth and development by repressing the expression level of its target growth-regulating factor (GRF) family genes. In our previous study, we found that overexpression of miR396 negatively regulated both tillering and biomass yield in switchgrass (Panicum virgatum L.). We, therefore, speculated that blocking the expression of miR396 could enhance switchgrass tillering and biomass yield. Here, we produced transgenic switchgrass plants overexpressing a target mimicry form of miR396 (MIM396) in wild type (WT) and Os-MIR319b overexpressing switchgrass plant (with higher enzymatic hydrolysis efficiency, but reduced tillering), in which the expression of miR396 was blocked. The phenotype and biological yields of these plants were analyzed. RESULTS: Blocking miR396 to improve its target PvGRFs expression in switchgrass improved the tiller number and dry weight of transgenic plants. Further morphological analysis revealed that MIM396 plants increased the number of aerial branches and basal tillers compared to those of wild-type plants. The enzymatic efficiency of MIM396 plants was reduced; however, the total sugar production per plant was still significantly higher than that of wild-type plants due to the increase in biomass. In addition, blocking miR396 in a transgenic switchgrass plant overexpressing Os-MIR319b (TG21-Ms) significantly increased the PvGRF1/3/5 expression level and tiller number and biomass yield. The miR156-target gene PvSPL4, playing a negative role in aerial and basal buds outgrowth, showed significant downregulated in MIM396 and TG21-Ms. Those results indicate that miR396-PvGRFs, through disrupting the PvSPL4 expression, are involved in miR319-PvPCFs in regulating tiller number, at least partly. CONCLUSIONS: MIM396 could be used as a molecular tool to improving tiller number and biomass yield in switchgrass wild type and miR319b transgenic plants. This finding may be applied to other graminaceous plants to regulate plant biological yield.

A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

Simultaneous and trace-level quantification of four benzene sulfonate potential genotoxic impurities in doxofylline active pharmaceutical ingredients and tablets using high-performance liquid chromatography with ultraviolet detection.

In the production of doxofylline, the common occurrence of toxic p-toluene sulfonate generation prompted the development and validation of a method using HPLC with ultraviolet detection (HPLC-UV). This method is designed for detecting four potential genotoxic impurities (PGIs) present in both doxofylline drug substance and tablets, with a focus on the UV-absorbing group p-toluene sulfonate. The four impurities were methyl 4-methylbenzenesulfonate (PGI-1), ethyl 4-methylbenzenesulfonate (PGI-2), 2-hydroxyethyl 4-methylbenzenesulfonate (PGI-3), and 2-(4-methylphenyl)sulfonyloxyethyl 4-methylbenzenesulfonate (PGI-4). In this method, chromatographic separation was achieved using a Waters Symmetry C18 column (250 mm × 4.6 mm, 5 µm). The mobile phases consisted of 20% acetonitrile as mobile phase A and pure acetonitrile as mobile phase B, operating in gradient elution mode at a flow rate of 1.0 mL/min. According to the guidelines of the International Conference on Harmonization, it was determined that this method could quantify four PGIs at 0.0225 µg/mL in samples containing 60 mg/mL. The validated approach demonstrated excellent linearity (R2 > 0.999) across the concentration range of 30%-200% (relative to 0.075 µg/mL doxofylline) for the four PGIs. The accuracy of this method for the four PGIs ranged from 94.8% to 100.4%. The reverse-phase-HPLC-UV analytical method developed in this study is characterized by its speed and precision, making it suitable for the sensitive analysis of benzene sulfonate PGIs in doxofylline drug substances and tablets.

Rasch analysis of the Hospital Anxiety andDepression Scale (HADS) in patients with major depression / Análisis de Rasch de la Escala Hospitalaria de Ansiedad y Depresión (Hospital Anxiety and Depression Scale, HADS) en pacientes con depresión mayor

La Hospital Anxiety and Depression Scale (HADS) [Escala Hospitalaria de Ansiedad y Depresión] es una herramienta ampliamente utilizada para detección de la depresión y la ansiedad en pacientes con enfermedades médicas. Este estudio tuvo como objetivo explorar las propiedades psicométricas de la HADS en la detección de pacientes con depresión mayor utilizando el método de la teoría de respuesta al ítem. Un total de 460 pacientes con depresión mayor completaron el HADS. Se utilizó el análisis de Rasch para examinar la unidimensionalidad, el ajuste de los ítems, la dependencia local, la confiabilidad, el orden de las categorías, el funcionamiento diferencial de los ítems (DIF) y la focalización. La HADS mostró una construcción bidimensional. Todos los ítems se ajustaban al modelo de Rasch. Tres pares de ítems mostraron una dependencia local menor pero desconsiderada. Ambas subescalas tuvieron una confiabilidad aceptable. Ninguno de los ítems mostró categorías desordenadas o DIF. Todos los ítems estaban bien dirigidos y los participantes con niveles altos y bajos de angustia fueron menos objetivo que aquellos con niveles moderados de angustia. Finalmente, se generó una tabla de conversión para transformar las puntuaciones brutas en medidas de intervalo. El HADS demostró propiedades psicométricas adecuadas para evaluar la depresión y la ansiedad en pacientes con depresión mayor. Fue más apropiado para evaluar niveles de angustia moderados que altos o bajos. La tabla de conversión se puede utilizar para una medición más precisa. Estos resultados pueden allanar el camino para métodos eficientes y sensibles para analizar la respuesta a los síntomas de depresión en la investigación y en la práctica clínica.(AU)

The Hospital Anxiety and Depression Scale (HADS) is a widely used screening tool for depression and anxiety in patients with medical ill-nesses. This study aimed to explore the psychometric properties of the HADS in screening for patients with major depression using item response theory method.A total of 460 patients with major depression completed the HADS. Rasch analyses were used to examine unidimensionality, item fit, local dependency, reliability, ordering of categories, differential item functioning (DIF)and targeting. The HADS showed a two-dimensional construct.All items fit the Rasch model.Three pairs of items showed mi-norbut inconsiderate local dependency.Both subscales had acceptable re-liability.None of the items displayed disordered categoriesor DIF.All items werewelltargeted, and participants with high and low levels of dis-tress were less targeted than those with moderate levels of distress.Finally, a conversion table to transform the raw scores into interval measures was generated. The HADS demonstrated adequate psychometric properties in assessing depression and anxiety in patients with major depression. It was more appropriate for assessing moderate than high or low levels of dis-tress.The conversion table can be used for more precise measurement.These results may pave the way for efficient and sensitive methods of ana-lyzing depression symptom response in research and in clinical practice.(AU)

A diagnostic approach integrated multimodal radiomics with machine learning models based on lumbar spine CT and X-ray for osteoporosis.

INTRODUCTION: The aim of this analysis is to construct a combined model that integrates radiomics, clinical risk factors, and machine learning algorithms to diagnose osteoporosis in patients and explore its potential in clinical applications. MATERIALS AND METHODS: A retrospective analysis was conducted on 616 lumbar spine. Radiomics features were extracted from the computed tomography (CT) scans and anteroposterior and lateral X-ray images of the lumbar spine. Logistic regression (LR), support vector machine (SVM), and random forest (RF) algorithms were used to construct radiomics models. The receiver operating characteristic curve (ROC) was employed to select the best-performing model. Clinical risk factors were identified through univariate logistic regression analysis (ULRA) and multivariate logistic regression analysis (MLRA) and utilized to develop a clinical model. A combined model was then created by merging radiomics and clinical risk factors. The performance of the models was evaluated using ROC curve analysis, and the clinical value of the models was assessed using decision curve analysis (DCA). RESULTS: A total of 4858 radiomics features were extracted. Among the radiomics models, the SVM model demonstrated the optimal diagnostic capabilities and accuracy, with an area under the curve (AUC) of 0.958 (0.9405-0.9762) in the training cohort and 0.907 (0.8648-0.9492) in the test cohort. Furthermore, the combined model exhibited an AUC of 0.959 (0.9412-0.9763) in the training cohort and 0.910 (0.8690-0.9506) in the test cohort. CONCLUSION: The combined model displayed outstanding ability in diagnosing osteoporosis, providing a safe and efficient method for clinical decision-making.

Rasch analysis of the Chinese version of the clinically useful depression outcome scale in patients with major depressive disorder.

OBJECTIVE: To examine the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale (CUDOS) in the Chinese patients with major depressive disorder (MDD) using Rasch analysis. METHODS: The sample consisted of 283 patients with MDD (69% females). The Rasch model was applied to examine the overall fit of the Chinese version of CUDOS and the fit of the 18 items. Dimensionality, item-model fit, differential item functioning (DIF), reliability, ordering of response category and targeting were tested to examine the psychometric properties of the Chinese version of CUDOS. RESULTS: Rasch analysis demonstrated the unidimensionality of the Chinese version of CUDOS. Of the 18 items, three items (item 4, item 5, item 6) showed misfit in the model. After merging item 4 into item 3 and item 6 into item 5, the overall model fit improved. The person separation index (PSI) was 3.0 and the person reliability coefficient was 0.90. No evidence of significant DIF was found when associated with gender and age. No disordered category and threshold of the rating response were observed, which meant the response category setting was reasonable. The mean ability of person was - 0.53. CONCLUSION: The results suggested that the Chinese version of CUDOS has acceptable psychometric properties. In order to improve the quality and applicability of the Chinese version of CUDOS, the merging of item 4 into item 3 and item 6 into item 5 are suggested.

Validation of the developmental, dimensional and diagnostic interview -short version (3Di-sv) for diagnosis of autism spectrum disorder in Chinese children.

The purpose of this study was to evaluate the psychometric features of the Chinese version of the developmental dimensional diagnostic interview-short version (3Di-sv). A total sample of 138 children including 79 children with autism spectrum disorder (ASD) and 59 typically developing children completed the 3Di-sv interview. The Chinese version of the 3Di-sv has a good internal consistency (0.94). Test-retest analysis confirmed the instrument's time stability (0.89). The instrument's concurrent validity with the Autism Behavior Checklist (ABC), the Childhood Autism Rating Scale (CARS) and clinical diagnosis was verified; the correlation between total scores was 0.72, 0.82 and 0.90, respectively. The 3Di-sv significantly distinguished between autistic children and non-autistic children in every area of autism symptoms. Optimal cutoffs were derived using receiver operating characteristics curves. Using clinical diagnosis as criterion, overall sensitivity was 98 % and specificity was 90 %. The study determined that the Chinese version of 3Di-sv can well distinguish autistic children from typically developing children.

Genome-wide identification and analysis of TCP family genes in Medicago sativa reveal their critical roles in Na+/K+ homeostasis.

BACKGROUND: Medicago sativa is the most important forage world widely, and is characterized by high quality and large biomass. While abiotic factors such as salt stress can negatively impact the growth and productivity of alfalfa. Maintaining Na+/K+ homeostasis in the cytoplasm helps reduce cell damage and nutritional deprivation, which increases a salt-tolerance of plant. Teosinte Branched1/ Cycloidea/ Proliferating cell factors (TCP) family genes, a group of plant-specific transcription factors (TFs), involved in regulating plant growth and development and abiotic stresses. Recent studies have shown TCPs control the Na+/K+ concentration of plants during salt stress. In order to improve alfalfa salt tolerance, it is important to identify alfalfa TCP genes and investigate if and how they regulate alfalfa Na+/K+ homeostasis. RESULTS: Seventy-one MsTCPs including 23 non-redundant TCP genes were identified in the database of alfalfa genome (C.V XinJiangDaYe), they were classified into class I PCF (37 members) and class II: CIN (28 members) and CYC/TB1 (9 members). Their distribution on chromosome were unequally. MsTCPs belonging to PCF were expressed specifically in different organs without regularity, which belonging to CIN class were mainly expressed in mature leaves. MsTCPs belongs to CYC/TB1 clade had the highest expression level at meristem. Cis-elements in the promoter of MsTCPs were also predicted, the results indicated that most of the MsTCPs will be induced by phytohormone and stress treatments, especially by ABA-related stimulus including salinity stress. We found 20 out of 23 MsTCPs were up-regulated in 200 mM NaCl treatment, and MsTCP3/14/15/18 were significantly induced by 10 µM KCl, a K+ deficiency treatment. Fourteen non-redundant MsTCPs contained miR319 target site, 11 of them were upregulated in MIM319 transgenic alfalfa, and among them four (MsTCP3/4/10A/B) genes were directly degraded by miR319. MIM319 transgene alfalfa plants showed a salt sensitive phenotype, which caused by a lower content of potassium in alfalfa at least partly. The expression of potassium transported related genes showed significantly higher expression in MIM319 plants. CONCLUSIONS: We systematically analyzes the MsTCP gene family at a genome-wide level and reported that miR319-TCPs model played a function in K+ up-taking and/ or transportation especially in salt stress. The study provide valuable information for future study of TCP genes in alfalfa and supplies candidate genes for salt-tolerance alfalfa molecular-assisted breeding.

Correlation of gut dominant microbiota with hyperuricemia. / åŸºäºŽç²ªä¾¿è‚ é“ä¼˜åŠ¿èŒç¾¤æ£€æµ‹æ•°æ®çš„é«˜å°¿é ¸è¡€ç—‡ç›¸å ³å½±å“å› ç´ åˆ†æž.

OBJECTIVES: To study the correlation of intestinal dominant flora with hyperuricemia, and to explore influencing factors of hyperuricemia. METHODS: Data of gut dominant microbiota were collected from subjects who underwent health check-up in Shulan (Hangzhou) Hospital from January 2018 to April 2020. Subjects with high uric acid and normal uric acid were matched by propensity score matching method according to age, gender and body mass index (BMI). This resulted in 178 pairs as hyperuricemia group and control group. The gut dominant microbiota between hyperuricemia and normal control group were compared. Pearson or Spearman correlation coefficient method was used to analyze the correlation between blood uric acid and intestinal dominant flora. Univariate and multivariate logistic regression were used to analyze the influencing factors of hyperuricemia. RESULTS: The abundance of Atopobium, Lactobacillus, Bacteroides, Enterococcus, Clostridium leptum, Fusobacterium prausnitzii, Bifidobacterium, Clostridium butyricum and the ratio of Bifidobacterium to Enterobacter (B/E) in the hyperuricemia group were significantly lower than those in the control group (all P<0.01). The correlation analysis showed that serum uric acid were negatively correlated with the abundance of Atopobium (r=－0.224, P<0.01), Bacteroides (r=－0.116, P<0.05), Clostridium leptum (r=－0.196, P<0.01), Fusobacterium prausnitzii (r=－0.244, P<0.01), Bifidobacterium (r=－0.237, P<0.01), Eubacterium rectale (r=－0.125, P<0.05), Clostridium butyricum (r=－0.176, P<0.01) and B/E value (r=－0.127, P<0.05). Multivariate logistic regression analysis showed that glutamyl transpeptidase was an independent risk factor for hyperuricemia (OR=1.007, 95%CI: 1.002-1.012, P<0.05), and the Atopobium was an independent protective factor for hyperuricemia (OR=0.714, 95%CI: 0.605-0.842, P<0.01). CONCLUSIONS: There are alterations in abundance of gut dominant microbiota in patients with hyperuricemia, and Atopobium abundance appears as a protective factor for hyperuricemia.

Use of Period Analysis to Timely Assess Five-Year Relative Survival for Patients with Ovarian Cancer from Taizhou, Eastern China.

OBJECTIVE: Ovarian cancer is a deadly gynecologic malignancy with a poor prognosis. It is essential to evaluate the early detection and screening programs of ovarian cancer via timely assessment of long-time survival, particularly in China where those data are incredibly limited. Here, we aimed to provide timely and accurately assessment of long-term survival estimate of ovarian cancer patients from eastern China. METHODS: Data of 770 ovarian cancer patients diagnosed between 2004-2018 were obtained from four cancer registries in Taizhou, eastern China, were included. We used period analysis to calculate five-year relative survival (RS) of aforementioned ovarian cancer patients for overall and the stratification by age at diagnosis and region. RESULTS: Our findings demonstrated that the overall five-year RS for ovarian cancer patients in Taizhou between 2014 and 2018 was 69.2%, while urban areas were higher compared to rural areas (77.6% vs. 64.9%). We also observed a significant age gradient with the five-year RS decreasing from 79.6% for age group < 55 years to 66.9% for age group > 74 years. Furthermore, we identified a clear upward trend of five-year RS over the study period, both overall and stratified by region and age at diagnosis. CONCLUSION: This is the first study in China using period analysis to provide the most up-to-date five-year RS for ovarian cancer patients from Taizhou, eastern China, which reaches 69.2% during 2014-2018. Our results provide valuable information for timely assessment of early detection and screening programs for ovarian cancer in eastern China.

RPS15A Mediates PI3K/AKT Signaling-Induced Parathyroid Cell Proliferation in Rats with Secondary Hyperparathyroidism.

OBJECTIVE: Ribosomal protein S15A (RPS15A) has been identified as a new oncogene in several tumors, but its functional role in secondary hyperparathyroidism (SHPT) characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation remains unclear. METHODS: A rat model of SHPT was successfully established with a high-phosphorus diet plus 5/6 nephrectomy. ELISA assay was used to determine PTH, calcium and phosphorus and ALP activity. Cell proliferation was analyzed by Cell counting Kit-8 (CCK-8) assay. Flow cytometry assay was utilized to determine cell cycle distribution and apoptosis in parathyroid cells. LY294002, an inhibitor of PI3K/AKT signaling, was used to elucidate the relationship between RPS15A and PI3K/AKT signaling. Immunohistochemical (IHC) staining, quantitative real time PCR and western blot analysis were applied to determine related molecular levels. RESULTS: Our data showed an upregulation of RPS15A and activated PI3K/AKT signaling pathway in the parathyroid gland tissues of SHPT rats, accompanied with increased PTH, calcium and phosphorus levels. Knockdown of RPS15A decreased parathyroid cell proliferation, induced cell cycle arrest and apoptosis. Treatment with LY294002 reversed the effects of pcDNA3.1-RPSH15A in parathyroid cells. CONCLUSIONS: Our study demonstrated RPS15A-mediated PI3K/AKT pathway as a novel molecular mechanism in the pathogenesis of SHPT, which may provide a new drug target in the future.

Clinical significance of serum CDC42 in the prediction of uremic vascular calcification incidence and progression.

Vascular calcification (VC) is prevalent in uremia patients, lacking effective molecular biomarkers. This study was conducted to explore the role of serum cell division cycle 42 (CDC42) in the diagnosis of uremic VC incidence and progression. We enrolled 104 uremia patients and selected arcus aortae calcification (AAC) as the outcome phenotype. Levels of CDC42, 1,25-dihydroxy vitamin D (1,25(OH) 2-D), fibroblast growth factor-23 (FGF-23), and other laboratory parameters in the blood were measured. The receiver operator characteristic curve, the Pearson test, and the multivariate Logistic regression were used for the analysis of CDC42 diagnostic values, correlation analysis, and screening of VC risk factors, respectively. CDC42 was higher in the serum of uremia patients with VC and elevated with the increase in AAC level. Serum CDC42 level>1.025 was predictive of VC incidence with 83.58% sensitivity and 56.76% specificity, and CDC42 level>1.280 was predictive of VC progression with 73.33% sensitivity and 68.18% specificity. Serum CDC42 was positively correlated with 1,25(OH) 2-D and FGF-23. Uremia patients with higher serum CDC42 had a higher probability of VC incidence and progression. Generally, serum CDC42 helped the diagnosis of uremic VC incidence and progression and was an independent risk factor for uremic VC progression.

The mediating effect of distress tolerance on the relationship between stressful life events and suicide risk in patients with major depressive disorder.

BACKGROUND: Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD. METHODS: A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk. RESULTS: The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect. CONCLUSION: Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD.

Characterization of gut dominant microbiota in obese patients with nonalcoholic fatty liver disease.

In obese patients, non-alcoholic fatty liver (NAFLD) is common. However, whether there is a connection between the gut microbiota and the onset of NAFLD in obese people is yet unknown. Using quantitative real-time PCR, the microbiota of feces of the eligible 181 obese individuals was identified to compare the differences in gut microbiota between obesity with NAFLD and simple obesity. According to the findings, the gut dominant microbiota was similar between obesity with NAFLD and simple obesity. Nonetheless, compared to the simple obesity group, the quantity of Faecalibacterium prausnitzii colonies was much lower in the obesity with the NAFLD group. Bacteroides were present in greater than 65% of both groups. Bacteroides, Clostridium leptum, and Clostridium butyricum accounted for more than 80% of the cases in the obesity with NAFLD group, whereas Bacteroides, Clostridium butyricum, and F. prausnitzii accounted for more than 80% of the cases in the simple obesity group. We look for potential contributing variables to obesity-related NAFLD and potential prevention measures for obese people. Based on a multi-factor logistic regression analysis, lymphocytes may be a risk factor for obesity with NAFLD while F. prausnitzii may be a protective factor. Additionally, F. prausnitzii is positively impacted by Bacteroides, Clostridium leptum, Clostridium butyricum, and Eubacterium rectale, yet adversely impacted by Enterobacteriaceae. Notably, lymphocytes and F. prausnitzii may help determine whether obese patients would develop NAFLD.

Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report.

The present study reports a patient case with a 17α-hydroxylase deficiency accompanied by triple X syndrome. A 17α-hydroxylase deficiency leads to a very low 17α-hydroxylated steroid synthesis as well as a non-feedback increase in the adrenocorticotropic hormone level. Meanwhile, the progesterone level increases the 17α-hydroxyprogesterone level and decreases the dehydroepiandrosterone sulfate level. The patient is characterized by intractable hypokalemia, high urinary potassium, hyperaldosteronemia, hyporeninemia, hypocortisolemia, hypertension, gonadal and secondary sexual dysplasia, a decreased estrogen level, primary amenorrhea, and infertility. The imaging findings indicate a presence of multiple bilateral adrenal gland adenomas, and the sequencing indicates a missense CYP17A1-E7 gene pathogenic variant. The karyotype is a 47, XXX [3]/46, XX [47] low-level chimeric karyotype. The patient's parents are cousins. To our knowledge, this patient is the first case diagnosed with congenital adrenal hyperplasia caused by hydroxylase deficiency and triple X syndrome. The uniqueness of this case is that this patient has two very rare genetic diseases, probably due to the marriage of close relatives.

Consensus of Chinese experts on strengthening personalized prevention and treatment of type 2 diabetes.

Up to now, there has not yet been guidance or consensus from Chinese experts in the field of personalized prevention and treatment of type 2 diabetes. In view of the above, the endocrinology diabetes Professional Committee of Chinese Non-government Medical Institutions Association, the integrated endocrinology diabetes Professional Committee of the integrated medicine branch of Chinese Medical Doctor Association, and the diabetes education and microvascular complications group of the diabetes branch of the Chinese Medical Association organized relevant experts to discuss and reach the "Chinese expert consensus on strengthening personalized prevention and treatment of type 2 diabetes" for reference in clinical practice.

Feasibility and safety of guidewire-balloon entrapment technique for recanalization of thoracic central vein occlusion in hemodialysis patients.

OBJECTIVE: To explore the feasibility and safety of Guidewire-Balloon Entrapment Technique (GBET) for the recanalization of thoracic central vein occlusions (TCVOs) in hemodialysis patients. METHODS: A retrospective observational study was conducted using data from 28 patients who required the establishment or maintenance of hemodialysis access and were treated with GBET for the recanalization of right-sided TCVOs from January 2017 to April 2021. Of the patients, 27 required tunneled cuffed catheter (TCC) placement or exchange, and 1 had an outflow tract occlusion of the Brescia-Cimino radio cephalic arteriovenous fistula (AVF). RESULTS: A total of 26 patients successfully underwent TCC exchange and placement using GBET; 1 patient underwent successful recanalization of an occlusion of the outflow tract of the right Brescia-Cimino AVF; and 1 patient underwent successful TCC placement in the left internal jugular vein (LIJV) after the failure of TCC placement in the right internal jugular vein (RIJV). The success rate for GBET was 27/28 (96.43%), and there were no major complications. CONCLUSION: GBET is a safe and effective method for the recanalization of right-sided TCVOs, especially for TCC exchange and placement, and can be used as a safe and easy approach for TCVO recanalization.