[Sensitivity of colorectal cancer organoids to hyperthermic intraperitoneal chemotherapy with lobaplatin].

Objective: To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method: Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 µmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 µmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 µmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result: Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 µmol/L (IQR: 1846.09 µmol/L). The median IC50 for lobaplatin was 85.04 µmol/L (IQR: 305.01 µmol/L).The difference between the two groups was not statistically significant (Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%‒47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%‒92.3%): this difference is statistically significant (t=‒15.282, P<0.001). Conclusion: The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

[Analysis of factors influencing the success rate of organoid culture in 1231 cases of colorectal cancer].

Objective: To investigate the risk factors for organoid culture failure in colorectal cancer. Methods: This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples. Results: The median (range) duration of organoid culture was 7 (3-12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant (P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335-0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285-0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154-63.131,P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112-61.882, P=0.039) were identified as independent protective factors. Conclusions: The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

[The influence of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-time gynecological laparoscopic tumor surgery].

Objective: To investigate the effect of different blood pressure management schemes on the quality of postoperative anesthesia recovery in elderly patients undergoing long-term gynecological laparoscopic tumor surgery. Methods: A total of 57 patients who underwent gynecological tumor surgery in Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine from May to October 2022 were prospectively included. The patients were randomly divided into two groups: the precise blood pressure management group [group P, n=28, aged (69.9±3.6) years] and the control group [group C, n=29, aged (68.6±3.1) years]. Group P adopted a precise blood pressure management scheme, and systolic blood pressure (SBP) fluctuated within±10% of basal blood pressure during operation, while group C adopted a routine blood pressure management scheme, which maintained SBP fluctuation within±20% of basal blood pressure during operation, and SBP≥90 mmHg (1 mmHg=0.133 kPa). The main outcome measures were the quality of anesthesia recovery (QoR-40) scores of the two groups 24 hours after the operation. The secondary outcome measures included lactate clearance rate and blood glucose change 2 hours after the beginning of the operation and immediately after the operation, post anesthesia recovery score (PARS) and sedation-agitation scale (SAS) 5 min after extubation, intraoperative norepinephrine dosage, volume of fluid administered, blood loss and urine volume, creatinine clearance rate and urea nitrogen clearance rate 24 hours after the operation, anesthesia satisfaction score, length of hospital stay and hospitalization cost, etc. Results: The QoR-40 score of group P [M (Q1, Q3)] 24 hours after operation was 192 (190, 195), which was higher than that of group C [170 (163, 178)] (P<0.001). The lactate clearance rates 2 hours after the beginning of the operation and immediately after the operation in group P [M (Q1, Q3)] were 31.0% (14.9%, 43.3%) and 21.1% (3.1%, 38.2%), which were higher than those in group C [-12.5% (-43.1%, 11.8%) and -22.2% (-61.3%, -11.1%)] (both P<0.05). The changes in blood glucose 2 hours after the beginning of the operation and immediately after the operation in group P [M (Q1, Q3)] were [1.1 (0.9, 1.4) mmol/L and 1.4 (0.9, 1.9) mmol/L], which were higher than those in group C [0.2 (-0.2, 0.5) mmol/L and 0.2 (-0.2, 0.5) mmol/L] (both P<0.05). The intraoperative urine volume, PARS score and SAS score 5 min after extubation, and anesthesia satisfaction score in group P [M (Q1, Q3)] were 400 (300, 500) ml, 8 (8, 9), 4 (4, 4) and 8 (8, 9), respectively, which were higher than those in group C [200 (100, 300) ml, 7 (7, 8), 3 (3, 3) and 6 (6, 7), respectively] (all P<0.05). There were no statistically significant differences in norepinephrine dosage, volume of fluid administered, blood loss, creatinine clearance rate, urea nitrogen clearance rate, length of hospital stay and hospitalization cost between the two groups (all P>0.05). Conclusion: The precise blood pressure management scheme of maintaining SBP fluctuation within±10% of basal blood pressure in elderly patients undergoing long-time gynecological laparoscopic tumor surgery can significantly enhance the quality of postoperative anesthesia recovery, improve the patients' satisfaction, and facilitate the patients' postoperative rehabilitation.

[Mechanism of VPS26 gene promoting implant osseointegration through Wnt/ß-catenin pathway in hyperlipidemia rats].

Objective: To investigate the mechanism of VPS26 effect on osteogenesis and adipogenesis differentiation of rat bone marrow mesenchymal stem cells (BMSC) in high fat environment, and to explore the effect of VPS26 on implants osseointegration of high fat rats and ectopic osteogenesis in nude mice. Methods: BMSC were cultured under normal osteogenic induction (osteogenic group) and high-fat osteogenic induction (high-fat group).High-fat group was transfected with VPS26 enhancer and inhibitor, and the expression levels of osteogenesis related genes and adipogenesis related genes were examined. Osteogenesis and adipogenesis of BMSC were detected by alkaline phosphatase (ALP) staining and oil red O staining after 7 and 14 days of induction.In osteogenic group,the binding of VPS26 to ß-catenin was detected by immunofluorescence staining and immunoprecipitation, and dual luciferase reporter assay (TOP Flash) was used to analyze the TOP/FOP ratio. Eighteen male 12-week hyperlipidemic Wista rats (160-200 g) were implanted with implants, and six in each group were injected with VPS26 overexpression lentivirus (LV-VPS26 group), negative control lentivirus (LV-nc group) and saline (blank control group).Micro-CT analysis , HE and oil red O staining were used to evaluate the osseointegration of the implants and lipid droplets formation of the femur samples. Twenty female 6-week nude mice (30-40 g) were divided into five groups and subcutaneously implanted with osteogenic BMSC non-transfected and transfected LV-VPS26, LV-nc, shVPS26, and shscr lentivirus on the back. Samples were used to observe ectopic osteogenesis. Results: The mRNA expression levels of ALP in the high-fat group BMSC after overexpression of VPS26 (1.56±0.09) were significantly higher than those of the negative control (1.01±0.03) (t=10.09, P<0.001), while those of peroxisome proliferator-activated receptor-γ (PPAR-γ) (t=6.44, P<0.001) and fatty acid-binding protein4 (FABP4) (t=10.01, P<0.001) were lower than those of the negative control. Western blotting results showed that compared with the negative control, protein expression of ALP and Runt-related transcription gene 2 was enhanced in the high-fat group BMSC after overexpression of VPS26 while PPAR-γ and FABP4 were inhibited. ALP activity of BMSC in the high-fat group was stronger after overexpression of VPS26, and the formation of lipid droplets was weaker than that in negative control. The results of immunofluorescence, immunoprecipitation and dual luciferase reporter assays showed co-localization and interaction of VPS26 with ß-catenin and a significant 43.10% increase in the TOP/FOP ratio (t=-3.17, P=0.034). VPS26 overexpression enhanced osseointegration and decreased the number of lipid droplets in high-fat rat and enhanced ectopic osteogenesis of nude mice. Conclusions: VPS26 activated osteogenesis differentiation and inhibited adipogenic differentiation of BMSCs through Wnt/ß-catenin pathway, promoting osseointegration of high-fat rat implants and ectopic osteogenesis of nude mice.

Does parental autonomy support mediate the relation between parent and infant executive function? A study of mothers and fathers in the Netherlands and China.

Parenting skills, such as Autonomy Support (AS), have been proposed as a potential mechanism explaining the intergenerational contiguity of Executive Function (EF). However, few studies have focused on mothers and fathers among non-Western families. The current study investigated the role of maternal and paternal AS in the relation between parental EF and infant EF at 14 months of age among 123 Dutch and 63 Chinese first-time mothers and fathers and their infants. Multiple-group structural equation models were built for mothers and fathers separately with country as a grouping variable. Results showed that parental AS did not mediate the relation between parent EF and infant EF at 14 months. Mean-level differences were found in parental AS, maternal EF, and infant inhibition across countries, while no country differences were found in the relation between parent EF, AS and infant EF. Our findings suggested that individual differences in early EF may not be stable enough to be reliably predicted from parental factors across the Netherlands and China.

Association of rs35006907 Polymorphism with Risk of Dilated Cardiomyopathy in Han Chinese Population.

Background: Several investigations have demonstrated the association of MTSS1 with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both MTSS1 expression and the risk of dilated cardiomyopathy (DCM). Objective: Our study intended to investigate the relationship between rs35006907 and the risk of DCM in the Han Chinese population. Methods: A total of 529 DCM and 600 healthy controls were recruited. We conducted genotyping for rs35006907 in all participants. Gene association studies were performed to assess the association between rs35006907 and the risk of DCM. A series of functional assays including western blot, realtime PCR and firefly luciferase reporter gene assays were conducted to illuminate the underlying mechanism. Results: We found that rs35006907-A allele was significantly associated with reduced risk of DCM in additive (p= 0.004; OR=0.78; 95% CI=0.66-0.93) and recessive models (p= 0.0005; OR=0.56; 95%CI=0.41-0.78) when compared with the rs35006907-C allele. There were significant differences in the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) between rs35006907-CC/AC and AA genotypes. Furthermore, the variant rs35006907-A allele presented lower reporter gene activity, reduced mRNA and protein expression levels when compared with the C allele. Conclusions: Our findings demonstrated that rs35006907-C allele increased the risk of DCM in Han Chinese population. Besides, rs35006907-C displayed higher reporter gene activity and increased MTSS1 expression in human samples.

Analysis results of 169 cases of chorionic villus samples of missed abortion using high throughput sequencing.

OBJECTIVE: This study aimed to evaluate the use of high-throughput sequencing (HTS) technology to detect chromosomes in chorionic villus samples of missed abortion embryos and investigate its utility in the genetic diagnosis of missed abortion. PATIENTS AND METHODS: HTS was used to assess chorionic villus samples obtained from 169 patients with missed abortions from August 2020 to March 2022, at the Second Affiliated Hospital of Guangxi Medical University. The test results were statistically analyzed. To investigate the impact of advanced age on the incidence of chromosomal abnormalities, the patients were divided into two groups: elderly (≥35 years) and nonelderly pregnant women (<35 years). RESULTS: (1) Among the samples of 169 patients, 100 (59.17%) cases of chromosomal abnormalities were detected. Among these 100, 90 (90%) had chromosomal numerical abnormalities and 10 (10%) had chromosomal structural abnormalities. (2) Chromosomal numerical abnormality was abnormalities mainly included aneuploidy (92.22%, 83/90), with trisomy (62.22%, 56/90) and monosomy (22.22%, 20/90) accounting for the majority. The top three numerical abnormalities included 18 cases of Turner syndrome (monosomy X; 20%, 18/90), 10 cases of trisomy 16 (11.11%, 10/90), and 10 cases of trisomy 22 (11.11%, 10/90). (3) Villous chromosomal abnormalities were found in 48 (70.59%) elderly pregnant women, and 52 (51.48%) nonelderly pregnant women, with statistically significant differences (p < 0.05). CONCLUSIONS: (1) Chromosomal abnormality is an important cause of missed abortion, it majorly includes chromosomal numerical abnormality, of which most cases are of aneuploidy. (2) Advanced age may increase the risk of embryonic chromosomal abnormalities. (3) Villus chromosome detection using HTS has a positive value and can be used for analyzing and determining the causes of missed abortion.

Narrative coherence across the transition to parenthood: Primiparous parents' representations of their child in relation to parental sensitivity.

Narrative coherence reflects parents' ability to provide a believable, clear, relevant, and internally consistent story about their child. Parents demonstrating more narrative coherence have been theorized to show higher parental sensitivity, but this has not been examined in a normative sample, nor across the transition to parenthood, and only once in fathers. The aim of this study was to examine stability and change in narrative coherence across the transition to parenthood in mothers and fathers, as well as the relation between pre- and postnatal narrative coherence and postnatal parental sensitivity. The sample consisted of 105 primiparous expecting parents. Narrative coherence was measured at 36-weeks pregnancy and when the child was 4 months old, using the Five Minute Speech Sample procedure. Parental sensitivity was observed in three episodes. Results demonstrated that narrative coherence was moderately stable (correlations) across the transition to parenthood in fathers only. Both mothers' and fathers' narrative coherence improved over time. Furthermore, mothers and fathers were overall equally coherent, and maternal and paternal narrative coherence were positively interrelated during pregnancy only. Lastly, our findings showed weak evidence for the theorized link between narrative coherence and parental sensitivity: only postnatal narrative coherence predicted paternal sensitivity, only during free play. Our findings give new insight in the development of narrative coherence across the transition to parenthood, and how it relates to actual parenting. More research is needed to confirm our findings and further explore this topic.

Genome Canada precision medicine strategy for structured national implementation of epitope matching in renal transplantation.

Advances in immunology support the understanding that precise structural epitopes on the antibody-accessible region of the HLA molecule determine antigenicity and challenge the need for identity across the full HLA molecule to minimize graft immunogenicity. Retrospective studies confirm that quantitative measurement of epitope-level mismatching between donor and recipient is an informative marker of graft rejection and survival and suggest that prospective allocation of donor organs based on this principle may improve graft survival. Here we describe the process for rigorous prospective evaluation of this hypothesis in a formal national proof-of-concept program for epitope-based matching. This encompasses broad societal consultation to engage the public, patients and providers; the development of clear allocation policies with strategies to support candidates who may be difficult to match; molecular and sequencing methods and web-based calculators enabling rapid epitope typing and recipient selection; precise immunological monitoring of the graft response; information systems permitting real-time monitoring of clinical outcomes; and assessment of health benefit and economic cost. The results of this objective evaluation can then be provided to payers and policy-makers for review, and adoption if of proven benefit.

Nerve growth factor orchestrates NGAL and matrix metalloproteinases activity to promote colorectal cancer metastasis.

PURPOSE: Colorectal cancer (CRC) is one most cancer type of high incidence and high mortality rate. Metastasis play an important role in survival rate and life quality of colorectal cancer patients. Nerve growth factor (NGF) has been shown to be involved in the metastasis and deterioration in many cancers, but the detail mechanisms in promoting the metastasis of colorectal cancer remain unknown. In this study, we aimed to explore the mechanism of NGF promoting colorectal cancer metastasis to provide new insights for developing NGF anti-colorectal cancer drugs. METHODS: We examined the expression of NGF in human colorectal cancer by immunohistochemical staining, and Western blot to evaluate the relationship between NGF and colorectal cancer metastasis. Using biochemical experiments including wound healing assay, transwell migration and invasion assay, RT-PCR, Western blot and ELISA to explore the relative mechanism of NGF promoting colorectal cancer cells metastasis in vivo. RESULTS: Our results found that the high expression of NGF was related with high incidence of metastasis. The binding of NGF to TrkA phosphorylated TrkA, which activated MAPK/Erk signaling pathway increasing the expression NGAL to enhance the activity of MMP2 and MMP9, promoted colorectal cancer metastasis. CONCLUSION: Our finding demonstrated that NGF increased NGAL expression to enhance MMPs activity to promoted colorectal cancer cell metastasis by TrkA-MAPK/Erk axis.

The role of infant attention and parental sensitivity in infant cognitive development in the Netherlands and China.

Infant attention and parental sensitivity are important predictors of later child executive function (EF). However, most studies have investigated infant and parent factors in relation to child EF separately and included only mothers from Western samples. The current study examined whether both infant attention at 4 months and parental sensitivity at 4 and 14 months were related to infant EF (i.e., inhibition, working memory, and cognitive flexibility) at 14 months among 124 Dutch and 63 Chinese first-time mothers and fathers and their infants. Findings revealed that parental sensitivity at 4 months was not correlated with infant EF abilities at 14 months. However, infant attention at 4 months was significantly related to 14-month working memory, but not to inhibition and cognitive flexibility. Maternal sensitivity at 14 months was significantly related to 14-month inhibition, but not to working memory and cognitive flexibility. No country differences were found in the relation among 4-month infant attention, parental sensitivity, and EF outcomes. Results show that both infant and parent factors are associated with early EF development and that these correlates of early EF skills may be similar in Western and non-Western samples.

[Analysing pathogenic bacterial spectrum and drug resistance of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation].

Objective: To elucidate the clinical characteristics of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital and improves the survival of transplant patients with bloodstream infection. Methods: Two hundred and ten patients with allo-HSCT from the Department of Hematology were retrospectively analyzed between October 2014 and September 2019. Pathogen distribution, drug resistance, risk factors, and outcomes were investigated in 49 allo-HSCT patients with bloodstream infections. Results: Forty-nine of 210 patients with allo-HSCT had bloodstream infection, and 59 pathogenic microorganisms were identified, mainly Gram-negative bacteria (67.8%) , of which E. coli had the highest incidence (23.7%) , CRO accounted for 42.5%, and Grampositive bacteria accounted for 23.7% (without vancomycin or linezolid-resistant strain) . Additionally, fungi accounted for 8.5%. Univariate analysis suggested that the risk factors of bloodstream infection were gender, pretransplant disease status, and conditioning regimen. In contrast, multivariate analysis showed that bloodstream infection was mainly related to conditioning regimens. Further grouping results showed that 77.6% of patients with neutropenia had bloodstream infections, and 22.4% of patients with non-neutropenia had bloodstream infections; 81.0% of patients with active infections before transplantation had bloodstream infections, while bloodstream infection occurred in 16.9% of patients without active infection. Survival analysis showed that long-term survival of patients with bloodstream infection is shorter than that of patients without bloodstream infection and long-term survival of patients with CRO infection is shorter than that of patients without CRO infection. The survival of patients with neutropenia longer than 14 d is shorter than that of patients with neutropenia shorter than 14 d. Furthermore, there is no correlation between whether there is an active infection before transplantation and whether they are in a neutropenic state at the time of infection and survival. Conclusion: Our results suggest that effective prevention of bloodstream infections from drug-resistant bacteria, particularly CRO, shortening the duration of neutropenia, eradication of potential infections before transplantation, and patient-adaptive conditioning could reduce transplant-related mortality and improve prognosis.

Regulator of cullins-1 (ROC1) negatively regulates the Gli2 regulator SUFU to activate the hedgehog pathway in bladder cancer.

BACKGROUND: The regulator of cullins-1 (ROC1) is an essential subunit in the cullin-RING ligase (CRL) protein complex and has been shown to be critical in bladder cancer cell survival and progression. This study aimed to explore the molecular mechanism of ROC1 action in the malignant progression of bladder cancer. METHODS: This study utilized ex vivo, in vitro, and in vivo nude mouse experiments to assess the underlying mechanisms of ROC1 in bladder cancer cells. The expression of the components of the sonic hedgehog (SHH) pathway was determined by western blot analysis. ROC1 expression in human tumors was evaluated by immunohistochemistry. RESULTS: ROC1 overexpression promoted the growth of bladder cancer cells, whereas knockdown of ROC1 expression had the opposite effect in bladder cancer cells. Mechanistically, ROC1 was able to target suppressor of fused homolog (SUFU) for ubiquitin-dependent degradation, allowing Gli2 release from the SUFU complex to activate the SHH pathway. Furthermore, knockdown of SUFU expression partially rescued the ROC1 knockdown-suppressed SHH activity as well as cancer cell growth inhibition. In ex vivo experiments, tissue microarray analysis of human bladder cancer specimens revealed a positive association of ROC1 expression with the SHH pathway activity. CONCLUSION: This study demonstrated that dysregulation of the ROC1-SUFU-GLI2 axis plays an important role in bladder cancer progression and that targeting ROC1 expression is warranted in further investigations as a novel strategy for the future control of bladder cancer.

Attitudes about child maltreatment in China and the Netherlands.

BACKGROUND: Definitions of child maltreatment vary between studies, and few are informed by research in non-Western countries. OBJECTIVE: We examined attitudes about child maltreatment in China and the Netherlands. PARTICIPANTS AND SETTING: The sample consisted of 304 participants from three groups (mothers, fathers, and teachers) and two countries (China and the Netherlands). METHODS: Participants completed the Maltreatment Q-sort in which 90 items reflecting four types of child maltreatment (physical abuse, emotional abuse, physical neglect, and emotional neglect) are divided in 9 stacks of 10 cards from least (1) to most (9) damaging to the child. RESULTS: The average within-country (r = .57) and within-group (r = .58) agreement about the order of harmfulness of the behaviors did not differ from the average between-country (r = .49) and between-group (r = .53) agreement. Physical abuse was seen as the most harmful form of child maltreatment and emotional neglect as the least harmful form (pƞ2 = .88). Higher thresholds were found for labeling the behaviors as child maltreatment, and the perceived need for intervention by a professional than for the need for intervention by a non-professional (pƞ2 = .67). These thresholds were higher for Chinese than for Dutch participants (pƞ2 = .31). CONCLUSIONS: The areas of agreement found are promising because successful collaboration within and between countries and groups could lead to more successful prevention and intervention of child maltreatment. The difference between China and the Netherlands however, stresses the importance of cultural sensitivity when implementing child maltreatment prevention and intervention programs.

[Survival status and influencing factors of HIV/AIDS cases in Liuzhou, 2008-2018].

Objective: To understand the duration of survival and related influencing factors of HIV/AIDS patients in Liuzhou city. Methods: Both life table method and Kaplan-Meier method were used to calculate the average survival time of HIV/AIDS patients aged ≥15 years reported in Liuzhou city from 2008 to 2018. Factors related to the duration of HIV/AIDS patients were analyzed by univariate and multivariate Cox regression models. Results: A total of 14 856 patients with HIV/AIDS were involved in this study and with the average duration of survival time as 98.74 (95%CI: 97.73-99.75) months. The cumulative survival rates of 1, 3, 5 and 10 years were 77.0%, 72.0%, 68.0%, 61.0% respectively. Results from the multivariate Cox proportional risk regression analysis showed that factors as sex, level of education, age when HIV infection was confirmed, occupation, route of transmission, source of samples, results of the first CD(4) test and antiviral treatment were all related to the duration of survival to the HIV/AIDS patients. Conclusions: Strategies involving early detection of HIV infection, improvement of the CD(4) initial detection rate and early antiviral treatment will help to significantly reduce the risk of death in HIV/AIDS population. Focus should be on male, middle-aged and elderly (over 41 years old), junior high school education or below farmers and migrant worker populations.

Diagnostic accuracy of fasting plasma glucose as a screening test for gestational diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: Fasting plasma glucose (FPG) is suggested as a potential screening test for further confirmatory testing by oral glucose tolerance test (OGTT) for diagnosing gestational diabetes mellitus (GDM). The diagnostic accuracy of FPG has been investigated in several studies with varying results. This meta-analysis is done to evaluate the diagnostic accuracy of FPG for the screening of GDM. MATERIALS AND METHODS: We conducted a systematic search for all studies reporting the diagnostic accuracy of FPG with OGTT as the reference standard in the databases of Medline, Scopus, Cochrane and Embase from inception till January 2020. Quality assessment of diagnostic accuracy studies-2 tool was used to assess the quality of trials. RESULTS: 29 studies with 74,481 patients were included. Eleven studies used the cut-off values of 92mg/dl for FPG to diagnose GDM, whereas 10 studies used the value of 92 mg/dl. The pooled sensitivity and specificity of FPG for cut-off ≥92 mg/dl was 68.6% (95% CI: 51.8%-81.9%), and 93.2% (95% CI: 80.5%-97.8%) respectively. The AUC was 0.88 (95% CI: 0.79-0.94). The pooled sensitivity and specificity of FPG for cut-off ≥90 mg/dl was 58.5% (95% CI: 41.1%-73.9%), and 89.2% (95% CI: 78.5%-94.9%) respectively. The AUC was 0.83 (95% CI: 0.75-0.91). The overall quality of studies was moderate. CONCLUSIONS: To summarize, our study found that FPG may have a role in the screening of GDM among pregnant women with satisfactory sensitivity and specificity at a cut-off of 92 mg/dl. Further studies exploring its accuracy in different ethnic populations in reference to a standard OGTT are required to strengthen the evidence.

MiR-205-3p protects human corneal epithelial cells from ultraviolet damage by inhibiting autophagy via targeting TLR4/NF-κB signaling.

OBJECTIVE: MiRNA has been found to have therapeutic effect on corneal damage. This paper aimed to study the effect of miR-205-3p on corneal damage induced by ultraviolet (UV) radiation. MATERIALS AND METHODS: HCE cells were exposed to UV light and transfected. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to determine miRNA/mRNA and protein expression. CCK-8 assay, Edu incorporation experiment, and flow cytometry were used to separately measure cell activity, proliferation and apoptosis. LC3 puncta were researched by immunofluorescence experiment. TNF-α, IL-6 and IL-1ß levels in cells were detected by enzyme-linked immunosorbent assay (ELISA) kit. MDA, SOD, and GSH-PX levels were measured using detection kits. Reactive oxygen species (ROS) level was reflected by detecting DCFH-DA density. Luciferase activity assay was performed to verify the regulating relationship between miR-205-3p and TLR4. RESULTS: UV radiation decreased HCE cell viability, proliferation, and increased HCE cell apoptosis and autophagy (all p < 0.01). When exposed UV radiation, the overexpression of miR-205-3p group elevated HCE cells viability, proliferation and weakened HCE cells apoptosis and autophagy (all p < 0.01). MiR-205-3p inhibited inflammation and oxidative stress in HCE cells induced by UV radiation (p < 0.01). MiR-205-3p directly inhibited TLR4 expression. The upregulation of TLR4 significantly reversed the effects of miR-205-3p on HCE cells phenotypes induced by UV radiation (p < 0.01). CONCLUSIONS: MiR-205-3p protected HCE cells from UV damage by inhibiting autophagy via targeting TLR4.