[Positive rates and distribution characteristics of pre-existing anti-human-leukocyte-antigen antibodies in patients with different hematological diseases].

Clinical data of 1 494 patients with hematological diseases who were scheduled to receive allogeneic hematopoietic stem cell transplantation and received the anti-human-leukocyte-antigen (HLA) antibody test for the first time at the First Affiliated Hospital of Soochow University from 2016 to 2018 was collected to analyze the positive rates and distribution characteristics of different types of pre-existing anti-HLA antibodies in patients with different hematological diseases. Among 1 494 patients with hematological diseases, there were 849 males and 645 females, aged [31 (17, 45)] years, and included 577 cases of acute myeloid leukemia (AML), 373 cases of acute lymphocytic leukemia (ALL), 234 cases of aplastic anemia (AA), 175 cases of myelodysplastic syndrome (MDS), and 135 cases of other diseases. The total positive rate of pre-existing anti-HLA antibodies was 25.1% (375/1 494), among which the positive rates of anti-HLA class Ⅰ, anti-HLA class Ⅱ, and anti-HLA class Ⅰ+Ⅱ antibodies were 11.2% (168/1 494), 4.9% (73/1 494), and 9.0% (134/1 494), respectively.The total positive rates of pre-existing anti-HLA antibodies in patients with MDS、AA、AML、ALL and other diseases were 40.6% (71/175), 30.8% (72/234), 26.2% (151/577), 12.3% (46/373), and 25.9% (35/135), respectively, with statistically significant difference (P<0.001). The positive rates of anti-HLA class Ⅰ, anti-HLA class Ⅱ, and anti-HLA class Ⅰ+Ⅱ antibodies in patients with different hematological diseases showed statistically significant differences (all P<0.001). Given the varying positive rates and distribution characteristics of pre-existing anti-HLA antibodies among patients with different hematological diseases, anti-HLA antibody test should be performed before receiving hematopoietic stem cell transplantation.

[SUV3 knockdown inhibits proliferation, migration, and invasion of hepatocellular carcinoma cells and induces PD-L1 expression].

Objective: To study the SUV3 gene role during the process of occurrence and advancement of hepatocellular carcinom. Methods: The The differences in SUV3 expression between hepatocellular carcinoma tissues and normal liver tissues were compared by analyzing transcriptome sequencing data from TCGA and GTEx databases. SUV3 knockdown in different hepatocellular carcinoma cells was performed using RNA interference technology. Overexpression vectors were constructed to overexpress SUV3 in different hepatocellular carcinoma cells. The SUV3 regulatory effect was studied on proliferation, migration, and invasion of hepatocellular carcinoma cells. A subcellular fraction isolation approach was used to investigate whether SUV3 knockdown resulted in the release of mitochondrial DNA into the cytoplasm. Quantitative reverse transcription PCR was applied to investigate whether SUV3 knockdown affected PD-L1 expression. The two groups were compared using a two-tailed t-test. Results: The TCGA database analysis revealed that SUV3 expression was higher in hepatocellular carcinoma tissues than in normal liver tissues, and the prognosis of patients with high SUV3 expression in hepatocellular carcinoma tissues was poor. The quantitative RT-PCR results showed that SUV3 expression was higher in hepatocellular carcinoma tissues than that in paracancerous liver tissue. The MTS assay showed that with SUV3 knockdown, the proliferation rate was significantly lower in hepatocellular carcinoma cells than that of the control hepatocellular carcinoma cells (P<0.01). The proliferation rate was significantly higher in SUV3-overexpressed hepatocellular carcinoma cells than that of control hepatocellular carcinoma cells (P<0.01). Cell scratch assay and cell migration and invasion assay showed that SUV3 knockdown inhibited the migration and invasion of hepatocellular carcinoma cells (P<0.01), while SUV3 overexpression promoted the migration and invasion of hepatocellular carcinoma cells (P<0.05). SUV3 Knockdown led to a decrease in the overall level of mtDNA (P<0.01) in accompanied by an increase in mtDNA level in the cytoplasm (P<0.01), indicating that SUV3 knockdown led to mitochondrial DNA leakage into the cytoplasm. SUV3 knockdown resulted in elevated PD-L1 expression (P<0.001), and overexpression of TREX1 in SUV3 knockdown cells decreased mtDNA levels in the cytoplasm and inhibited SUV3 knockdown, resulting in elevated PD-L1 expression, indicating that SUV3 knockdown induced PD-L1 expression by increasing cytoplasmic DNA levels. Conclusions: The SUV3 gene may play an oncogenic function in hepatocellular carcinoma cells.

[Swertiamarin ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis in mice by inhibiting intestinal epithelial cell apoptosis].

OBJECTIVE: To investigate the mechanism by which swertiamarin (STM) ameliorates CD-like colitis in mice. METHODS: A Caco-2 cell model of TNF-α-stimulated apoptosis was established and divided into three groups: Con, TNF-α and STM, and the effects of STM on apoptosis and barrier function were assessed by Tunel staining, western blotting, immunofluorescence, and transepithelial electric resistance (TEER). A mouse model of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) -induced CD-like colitis was established to assess the effects of STM on colitis, intestinal barrier function and epithelial cell apoptosis. The regulatory role of the PI3K/AKT pathway in STM-induced resistance to intestinal epithelial cell apoptosis was investigated in both the cell model and mouse models. RESULTS: TUNEL staining showed that in Caco-2 cells with TNF-α stimulation, STM treatment significantly reduced the percentage of TUNEL-stained cells (P<0.05). STM obviously reduced TNF-α-induced enhancement of cleaved-caspase 3 and Bax expressions (P<0.05), increased Bcl-2 expression (P<0.05), protected intestinal barrier integrity and function by restoring transepithelial electrical resistance (TEER) of the cells, promoted normal localization and expressions of the tight junction proteins (ZO1 and claudin 1) (P<0.05), and inhibited the expression of pro-inflammatory factors (IL-6 and CCL3) (P<0.05) in TNF-α-stimulated Caco-2 cells. In the mouse models, STM significantly alleviated TNBS-induced CD-like colitis and intestinal barrier dysfunction (P<0.05) as shown by improved weight loss, lowered Disease Activity Index (DAI) score and inflammation score, reduction of IL-6 and CCL3 release, and restoration of intestinal barrier permeability, colonic TEER, bacterial translocation, and localization and expressions of the tight junction proteins. Mechanistically, STM inhibited the expressions of p-PI3K and p-AKT in both the cell model and mouse model(P<0.05), and treatment with 740Y-P (a PI3K/AKT pathway activator) significantly attenuated the inhibitory effect of STM on TNF-α-induced apoptosis in Caco-2 cells (P<0.05). CONCLUSION: STM inhibits intestinal epithelial cell apoptosis at least in part by suppressing activation of the PI3K/AKT pathway to ameliorate intestinal barrier dysfunction and colitis in mice.

Identification of molecular subtypes for endometrial carcinoma using a 46-gene next-generation sequencing panel: a retrospective study on a consecutive cohort.

BACKGROUND: Traditional classification tools for endometrial carcinoma (EC), such as DNA sequencing, immunohistochemistry (IHC), or PCR, are cumbersome and time-consuming. Large next-generation sequencing (NGS) panels have simplified testing but are expensive. In this study, we propose a concise NGS panel as an effectively viable approach for classifying EC. MATERIALS AND METHODS: We retrospectively enrolled a consecutive EC cohort of hysterectomy with bilateral salpingo-oophorectomy from Fudan University Shanghai Cancer Center between 2020 and 2022. A 46-gene NGS panel was utilized to identify POLE exonuclease domain mutations, microsatellite instability-high (MSI-H), TP53 mutations, and other clinically relevant targets. RESULTS: Tumor tissue samples from 331 EC patients were evaluated, with 284 (85.8%) cases classified as endometrioid endometrial carcinoma. The median follow-up time was 32.6 months (n = 303), during which 23 patients experienced recurrence or disease progression. Using the concise NGS panel, patients were stratified into four molecular subgroups according to the World Health Organization classification criteria: POLE mut (n = 47; 14.2%), mismatch repair deficiency (dMMR) (n = 79; 23.9%), non-specific molecular profile (n = 148; 44.7%), and abnormal p53 expression (p53 abn) (n = 57; 17.2%). POLE mut displayed the most favorable prognosis, while p53 abn had the worst prognosis (P < 0.001). The concordance between NGS and IHC was 91.8% (269/293) for detecting MMR status and 65.3% (201/308) for detecting p53 status. Patients detected solely by NGS had significantly worse prognosis than those detected solely by IHC, indicating higher accuracy of the NGS panel. With the molecular subtyping information, adjuvant treatment plans for 19.6% of patients could potentially be altered, mainly concentrated in the POLE mut and p53 abn subtypes. This panel also aids targeted therapy and poly (ADP-ribose) polymerase (PARP) inhibitor-related gene mutation detection, as well as auxiliary genetic screening. CONCLUSION: Our study demonstrates that the concise NGS panel is an effective 'one-stop' strategy for precisely classifying EC with high clinical availability.

Use of birth weight as a predictor of genetic merit of subsequent growth traits in Duroc and Landrace pigs.

Analysis of correlation between the early testable phenotypes of piglets and the final performance of pigs can serve the early selection for breeding. The objectives of this study were to estimate the genetic parameters for birth weight (BtW), age (AGE) and backfat thickness (BF) up to 115 kg BW and to analyse the relationships among these three traits, and to estimate the accuracy of using BtW to predict estimated breeding values (EBVs) of AGE and BF in Landrace and Duroc pigs. Data on 26 614 Landrace and 19 984 Duroc pigs, born between 2001 and 2018, were collected from the core breeding group of a farm. All pigs were recorded for phenotypes including BtW, AGE and BF. The factors affecting these three traits were analysed using R v4.2.0 Software. The population genetic parameters and breeding values of three traits were estimated by using a multitrait animal model based on AI plate of DMU software. Heritabilities for BtW, AGE and BF were moderate to high for Landrace (0.437, 0.282and 0.137, respectively) and Duroc breeds (0.369, 0.279 and 0.148). BtW was genetically correlated with AGE and BF in Landrace (-0.213, 0.037) and Duroc (-0.214, 0.025). AGE was negatively genetically correlated with BF in both Landrace (-0.036) and Duroc (-0.057) pigs. The heritability of BtW, AGE and BF of Landrace pigs and Duroc pigs were 0.148, 0.182 and 0.075 and 0.168, 0.159 and 0.120, respectively, by taking into account of the litter effect. BtW was genetically correlated with AGE and BF in Landrace (-0.094, 0.002) and Duroc (-0.199, -0.052). AGE was negatively genetically correlated with BF in both Landrace (-0.034) and Duroc (-0.153) pigs. The variances between total individual BtW and AGE and BF were then used to predict the EBV of AGE and BF for individuals with AGE or BF phenotypes missing under 10-fold cross-validation. Prediction accuracy was calculated as the Kendall tau-b correlation coefficient between EBVs and EBVs via 10-fold cross-validation. Prediction accuracy for AGE and BF was 0.655 and 0.611 in Landrace, 0.665 and 0.617 in Duroc. After incorporation of the litter effect, the prediction accuracy for AGE and BF increased to 0.690 and 0.665 in Landrace and to 0.705 and 0.649 in Duroc. So, the EBV of AGE and BF phenotypes missing individuals could be predicted by using the available phenotypic data and the easily measured BtW, and litter effect could boost the accuracy of prediction.

[Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy].

Objective: To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy. Methods: This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group,a 1︰2 match was performed using the propensity score matching method,and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fishier's exact test were used to compare the data between the two groups,respectively. Results: After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant (t=-3.800,P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml;U=1 026.500,P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28)in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups(P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the groups(P=0.532,P=0.927). Conclusion: The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

[Analysis of clinical characteristics and curative effects of 169 patients with bilateral sudden sensorineural hearing loss].

Objective: To analyze the clinical characteristics, curative effect related factors and follow-up situation of bilateral sudden sensorineural hearing loss (BSSHL). Methods: The clinical data of 169 patients(338 ears) with BSSHL were retrospectively summarized, and the demographic characteristics, predisposing factors, concomitant symptoms and diseases, and audiological characteristics were statistically described. Additionally, influencing factors of curative effect and prognosis were statistically analyzed. Results: Among the 169 patients, 50.9% (86/169) of patients had at least one incentive, with cold and fatigue being the most common incentives(both 23/169). There were high rates of accompanying symptoms including tinnitus (150/169, 88.8%) and dizziness (100/169, 59.2%). Hypertension(49/169, 29.0%)and diabetes(23/169, 13.6%)were the most common concomitant diseases observed. Most cases exhibited all frequencies involvement, with flat type and total deafness type accounting for 83.1%(281/338 ears). The most common degree of hearing loss was total deafness(86/338 ears), with approximately 60.1%(203/338 ears) of the cases being severe or worse. The total effective rate of treatment was only 29.0%, but it increased to 39.5% for patients with course of disease≤14 days, however, when course of disease>30 days, the effective rate decreased sharply to 3.6%, showing a significant difference between these two groups(χ2=13.776,<0.01). Different types of hearing curves showed statistically significant difference in efficiency(χ2=14.782, P<0.01). Comparing the hearing improvements of 28 BSSHL patients from admission to discharge and from discharge to follow-up, it was found that the hearing improvement of the two groups showed statistically significant difference at the frequencies of L-250 Hz, L-500 Hz, R-125 Hz, R-250 Hz and R-500 Hz(Z value was -2.495, -3.083, -3.970, -3.388 and -3.264 respectively, all P<0.05). The proportion of patients with elevated serum IgE was much higher than that of the normal population. Conclusion: BSSHL patients suffer from serious hearing loss, and many also experience tinnitus and vertigo symptoms. Due to the poor efficiency of treatment, it is better for patients to be treated within 30 days of onset. For patients of hearing loss in the low frequency range, hearing improvement is more significant during hospitalization. And the occurrence of BSSHL may involve an immune mechanism.

A bright burst from FRB 20200120E in a globular cluster of the nearby galaxy M81.

Fast radio bursts (FRBs) are immensely energetic millisecond-duration radio pulses. Observations indicate that nearby FRBs can be produced by old stellar populations, as suggested by the localization of the repeating source FRB 20200120E in a globular cluster of M81. Nevertheless, the burst energies of FRB 20200120E are significantly smaller than those of other cosmological FRBs. Here, we report the detection of a bright burst from FRB 20200120E in 1.1 - 1.7 GHz, with a fluence of approximately 30 Jy ms, which is more than 42 times larger than the previously detected bursts near 1.4 GHz frequency. It reaches one-third of the energy of the weakest burst from FRB 20121102A and is detectable at a distance exceeding 200 Mpc. Our finding bridges the gap between nearby and cosmological FRBs and indicates that FRBs hosted in globular clusters can be bright enough to be observable at cosmological distances.

Experimental study on the effect of light source arrangements on the disinfection performance of upper-room 222 nm Far-UVC.

The air disinfection efficacy of upper-room 222 nm Far-UVC was experimentally investigated in a real-size chamber under well-mixed air conditions. Two bacteria (Escherichia coli, Staphylococcus epidermidis) and two bacteriophages (MS2, and P22) were selected for the test. The study considered different lamp source arrangements, including single and double sources, stationary and rotating operating modes, and an overlapping mode with a 45° irradiation angle. A numerical view-factor model was developed to analyze the irradiance distributions. Four irradiation angles, 30°, 45°, 60°, and 90°, were chosen. The results show that the lamps operating with an irradiation angle of 45° provide the highest chamber-averaged irradiance. This suggests an optimal irradiance level for a given room dimension, as inferred from the view factor model. Experimental results indicated that the overlapping mode with a 45° irradiation angle consistently outperformed both the stationary mode and rotating mode in disinfection. This can be attributed to the higher chamber-averaged irradiance, which is also supported by the numerical model predictions. The increment ratios ranged from 14.9 % to 42.9 % compared to the stationary mode. The susceptibility constants of Escherichia coli, Staphylococcus epidermidis, MS2, and P22 were measured as 0.572 m2/J, 0.099 m2/J, 0.060 m2/J, and 0.081 m2/J respectively.

Detecting pulmonary malignancy against benign nodules using noninvasive cell-free DNA fragmentomics assay.

BACKGROUND: Early screening using low-dose computed tomography (LDCT) can reduce mortality caused by non-small-cell lung cancer. However, ∼25% of the 'suspicious' pulmonary nodules identified by LDCT are later confirmed benign through resection surgery, adding to patients' discomfort and the burden on the healthcare system. In this study, we aim to develop a noninvasive liquid biopsy assay for distinguishing pulmonary malignancy from benign yet 'suspicious' lung nodules using cell-free DNA (cfDNA) fragmentomics profiling. METHODS: An independent training cohort consisting of 193 patients with malignant nodules and 44 patients with benign nodules was used to construct a machine learning model. Base models using four different fragmentomics profiles were optimized using an automated machine learning approach before being stacked into the final predictive model. An independent validation cohort, including 96 malignant nodules and 22 benign nodules, and an external test cohort, including 58 malignant nodules and 41 benign nodules, were used to assess the performance of the stacked ensemble model. RESULTS: Our machine learning models demonstrated excellent performance in detecting patients with malignant nodules. The area under the curves reached 0.857 and 0.860 in the independent validation cohort and the external test cohort, respectively. The validation cohort achieved an excellent specificity (68.2%) at the targeted 90% sensitivity (89.6%). An equivalently good performance was observed while applying the cut-off to the external cohort, which reached a specificity of 63.4% at 89.7% sensitivity. A subgroup analysis for the independent validation cohort showed that the sensitivities for detecting various subgroups of nodule size (<1 cm: 91.7%; 1-3 cm: 88.1%; >3 cm: 100%; unknown: 100%) and smoking history (yes: 88.2%; no: 89.9%) all remained high among the lung cancer group. CONCLUSIONS: Our cfDNA fragmentomics assay can provide a noninvasive approach to distinguishing malignant nodules from radiographically suspicious but pathologically benign ones, amending LDCT false positives.

Selective recovery of antimony from Sb-bearing copper concentrates by integration of alkaline sulphide leaching solutions and microwave-assisted heating: A new sustainable processing route.

The technical feasibility of leaching antimony from an antimony-bearing copper sulphide concentrate, using alkaline sulphide solutions and microwave-assisted and non-assisted heating technology, is investigated at a laboratory scale. The leaching test examines the influence of selective leaching reagent (Na2S and NaOH) concentrations, solid/liquid ratio, and temperature. The results indicate that antimony dissolution is highly selective (e.g. only Sb and As are leached), depending on the concentrations of leaching reagents and the leaching temperature. The influence of temperature on the mineral's dissolution, in the range 25-140 °C, is analysed from a thermochemical point of view using equilibrium databases. Under the optimal conditions: leaching agent: 250 g/L Na2S, 60 g/L NaOH, 2 h, 140 °C, with microwave assisted, the leaching efficiency of Sb reached 95.7 %. The antimony content in the copper concentrate is successfully reduced from 1.1 wt% to <0.2 wt% Sb, making it suitable for copper concentrate metallurgical processing. The study demonstrates that increasing temperature and NaOH/Na2S concentrations collectively enhance leaching efficiency, with a statistical significance, reducing both leaching time and the required temperature, compared to non-microwave-assisted leaching. Furthermore, it is established that excess free hydrogen sulphide ions ensure the efficient dissolution of the main impurities associated with penalties, such as antimony and arsenic, with limited copper and iron dissolution from the copper concentrate, predominantly chalcopyrite. Finally, an integrated hydrometallurgical process flowsheet for antimony removal and recovery from a sulphide copper concentrate is proposed.

Improved diet-based nutritional interventions can improve childhood obesity with the synergistic regulation of gut microbiota.

Childhood obesity is a crucial public health concern worldwide. Dietary intervention is the most common intervention for the treatment of obesity. Therefore, we tested an improved diet-based nutritional interventions to improve the childhood obesity and its gut microbiota. Thirty obese children received a 12-week intervention with the adjust-energy-restricted dietary pattern (A-CRD). Body composition was measured by bioelectrical impedance (Inbody S10) and faecal microbes were profiled by sequencing 16S rRNA. Compared to the NTB group (at 0 week), the NTA group (at 12 weeks) had a significantly greater decrease in body weight, body mass index (BMI) and percent body fat (PBF) ( P < 0.001, respectively), whereas skeletal muscle mass (SMM) and fat free mass (FFM) were not statistically significantly different ( P > 0.05). The gut microbiota was found significantly different between the NTB and NTA groups based on alpha and beta diversity. Bifidobacterium, Blautia, and Streptococcus was significantly increased, whereas Bacteroides and Megamonas was significantly decreased in the NTA group ( P < 0.05, respectively). Meanwhile, NTA group significantly increased the ability to produce short-chain fatty acids (SCFAs; e.g. acetic acid/total dietary energy) and changed he predictive metabolic functional features of the microbiota communities ( P < 0.05, respectively) than the NTB group. In conclusion, A-CRD can significantly improve childhood obesity, and the underlying mechanism may be its effect on gut microbiota and metabolism. Therefore, the diet-based nutrition intervention targeting gut microbiota will be more effective management of body weight and prevention of obesity. Chinese Clinical Trial Register: ChiCTR2300074571.

[3-Methyladenine alleviates early renal injury in diabetic mice by inhibiting AKT signaling].

OBJECTIVE: To explore the mechanism of 3-methyladenine (3-MA) for alleviating early diabetic renal injury. METHODS: Mouse models of streptozotocin (STZ) -induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks, respectively. Body weight and fasting blood glucose of the mice were recorded every week. After the treatments, the kidneys of the mice were collected for measurement kidney/body weight ratio, examination of glomerular size with PAS staining, and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry. SV40 MES 13 cells cultured in normal glucose (5.6 mmol/L) and high glucose (30 mmol/L) were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h, respectively, and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting. Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease (DKD) and 3-MA was performed, and the results were verified by Western blotting both in vivo and in vitro. RESULTS: In the diabetic mice, treatment with 3-MA produced a short-term hypoglycemic effect, reduced the kidney/body weight ratio and glomerular hypertrophy, and decreased the expressions of α­SMA and PCNA in the renal cortex. In the in vitro study, 3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose. The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD. Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells. CONCLUSION: 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.

[Research progress on the association between screen content and mental health issue in children and adolescents].

With the wide use of screen media, screen exposure shows a trend of younger age, and the screen exposure of children and adolescents has become a global public health issue of concern. Childhood and adolescence are important stages of growth and development, as well as critical periods of cognitive ability, emotional development and socialization. Previous studies have shown that screen time is closely related to the mental health of children and adolescents, but few studies have focused on the correlation between screen content and their mental health. The screen content for children and adolescents mainly comes from traditional TV and emerging interactive electronic media. Children and adolescents are highly sensitive to screen content. This paper summarizes the current situation of screen content for children and adolescents and reviews the correlation between screen content and their mental health issues. It also reveals the potential mechanism of the correlation between the two to provide a theoretical basis for the selection and supervision of screen content for children and adolescents.

A risk-prediction score about colorectal lesions based on the Chinese population of high-risk participants aged 50-65 years.

OBJECTIVES: The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC). STUDY DESIGN: Screening for colorectal lesions. METHODS: 14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set. RESULTS: In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001). CONCLUSION: Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.