m5 C and m6 A modification of long noncoding NKILA accelerates cholangiocarcinoma progression via the miR-582-3p-YAP1 axis.

Cholangiocarcinoma (CCA) is a severe malignancy originating from the bile duct and the second most common primary liver cancer. NF-kappa B interacting lncRNA (NKILA) is a functional lncRNA, which play important role in human cancers. However, the role and underlying mechanism of NKILA in CCA remains largely unknown. Here, our study demonstrated that NKILA was significantly upregulated in CCA tissues and cells. Overexpression of NKILA is associated with advanced TNM stage, lymph node and distant metastasis, and also indicated poor prognosis in CCA patients. Functionally, NKILA facilitated CCA growth and metastasis in vitro and in vivo. The 5-methylcytosine (m5 C) methyltransferase NSUN2 interacts with NKILA, increasing its m5 C level and promoting its interaction with YBX1. Moreover, NKILA physically interacted with and suppressed miR-582-3p, which was regulated by METTL3-mediated N6 -methyladenosine (m6 A) modification. Finally, we showed that YAP1 was a target of NKILA via miR-582-3p and NKILA functioned partially via YAP1 in CCA. Taken together, our findings indicate a novel regulatory mechanism of NKILA for promoting CCA progression and that NKILA may be a promising target for CCA treatment.

Cucurbituril-Ferrocene: Host-Guest Based Pretargeted Positron Emission Tomography in a Xenograft Model.

Pretargeted positron emission tomography is a macromolecule-driven nuclear medicine technique that involves targeting a preadministered antigen target-bound macromolecule with a radioligand in vivo, aiming to minimize the overall radiation dose. This study investigates the use of antibody based host-guest chemistry methodology for pretargeted positron emission tomography. We hypothesize that the novel pretargeting approach reported here overcomes the challenges the current pretargeting platforms have with the in vivo stability and modularity of the pretargeting components. A cucurbit[7]uril host molecule modified, anti-carcinoembryonic antigen antibody (M5A; CB7-M5A) and a 68Ga-radiolabeled ferrocene guest radioligand ([68Ga]Ga-NOTA-PEG3-NMe2-Fc) were studied as potential host-guest chemistry pretargeting agents for positron emission tomography in BxPC3 xenografted nude mice. The viability of the platform was studied via in vivo biodistribution and positron emission tomography. Tumor uptake of [68Ga]Ga-NOTA-PEG3-NMe2-Fc was significantly higher in mice which received CB7-M5A prior to the radioligand injection (pretargeted) (3.3 ± 0.7%ID/g) compared to mice which only received the radioligand (nonpretargeted) (0.2 ± 0.1%ID/g).

Prediction of 10-year atherosclerotic cardiovascular disease risk among community residents in Shanghai, China - a comparative analysis of risk algorithms.

BACKGROUND AND AIMS: The accuracy of various 10-year atherosclerotic cardiovascular disease (ASCVD) risk models has been debatable. We compared two risk algorithms and explored clustering patterns across different risk stratifications among community residents in Shanghai. METHODS AND RESULTS: A total of 28,201 residents (aged 40-74 years old) who were free of ASCVD were selected from the Shanghai Survey in China. The 10-year ASCVD risk was estimated by applying the 2013 Pooled Cohort Equations (PCEs) and Prediction for ASCVD Risk in China (China-PAR). The agreement was assessed between PCEs and China-PAR using Cohen's kappa statistics. The mean absolute 10-year ASCVD risk calculated by PCEs and China-PAR was about 10.0% and 6.0%, respectively. PCEs estimated that 44.9% of participants [with a 95% confidence interval (CI):44.0%-45.8%] were at high risk, while China-PAR estimated only 16.7% (95%CI:15.8%-18.0%) were at high risk. In both models, the percentage of high ASCVD risk was higher for participants who were older, men, less educated, current smokers, drinkers and manual workers. Among high-risk individuals, almost all participants (PCEs:90.5%; China-PAR:98.6%) had at least one risk factor; hypertension being the most prevalent. The concordance between PCEs and China-PAR was moderate (kappa:0.428, 95%CI: 0.420-0.434) with a better agreement for women (kappa:0.503,95%CI: 0.493-0.513) than for men (kappa:0.211,95%CI: 0.201-0.221). CONCLUSION: The proportion of participants with a 10-year ASCVD high risk predicted by China-PAR was lower than the results of the PCEs. The risk stratifications of the two algorithms were inconsistent in terms of demographic and life-behaviour characteristics.

Sleep quality of Shanghai residents: population-based cross-sectional study.

OBJECTIVE: To estimate the prevalence of poor sleep and its risk factors for adults living in a suburban area of Shanghai with rapid urbanization. METHODS: A total of 37,545 residents who were aged 20 to 74 years and from the "Peak Program," a community-based natural population cohort study, were included. Data on demographics, lifestyle, and physical health-related factors were collected using a face-to-face questionnaire interview. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and poor sleep was defined as a PSQI score above 7. RESULTS: The overall mean of PSQI score was 3.69 ± 2.57 while the prevalence of poor sleep was 8.3%. The prevalence of poor sleep quality was higher in participants who were older than 40 years, had less education, smoked tobacco, had anxiety, and had a chronic disease (p < 0.05 for all comparisons). After adjustment for confounding, a logistic regression model indicated that poor sleep was associated with advanced age, smoking, anxiety, cardiovascular and cerebrovascular diseases, respiratory diseases, and other chronic diseases (p < 0.05 for all comparisons). In addition, compared to women who were premenopausal, the naturally postmenopausal women (OR 1.675, 95% CI 1.44-1.94) and induced menopausal women (OR 2.26, 95% CI 1.81-2.82) were more likely to report poor sleep. CONCLUSION: The prevalence of poor sleep among individuals who lived in the Songjiang District of Shanghai and were aged 20 to 74 years was remarkably lower than in the general population of China. Poor sleep was generally more common in middle-aged and elderly residents and in those suffering from anxiety and chronic diseases. Regular exercise, anxiety relieving, and treatment improvement of different chronic diseases may help sleep better.

Association of Metabolic Syndrome and Its Components with Decreased Estimated Glomerular Filtration Rate in Adults.

BACKGROUND/AIMS: Metabolic syndrome (MetS) and its metabolic components, the common risk factors, may be involved in the development and progression of decreased estimated glomerular filtration rate (eGFR). The aim of this study was to examine the association of MetS and its metabolic components with eGFR status and severity among Chinese adults. METHODS: The population-based, cross-sectional study recruited a total of 33,300 Chinese adults (aged ≥18 years) from 4 study community sites in Songjiang District, Shanghai, between June 2016 and December 2017. Decreased eGFR was defined as a value of eGFR below 60 mL/min/1.73 m2. Weighted multiple logistic regression models were used to examine the association of MetS and its components with eGFR status and severity. RESULTS: After adjusting for potential confounders, subjects with MetS had an increased risk of decreased eGFR with an adjusted OR of 1.76 (95% CI 1.53-2.01), and subjects with increasing numbers of MetS components had a gradually increased risk for decreased eGFR (p trend <0.001). The multivariable-adjusted ORs (95% CI) of decreased eGFR were 1.66 (1.44-1.93) for abdominal obesity, 1.37 (1.18-1.60) for elevated triglycerides, 1.13 (0.96-1.33) for reduced high-density lipoprotein cholesterol, 0.84 (0.72-0.98) for elevated fasting glucose, and 1.92 (1.57-2.35) for elevated blood pressure (BP). Furthermore, these associations remained in most of the subgroups analyses. Significant associations between elevated BP and the risks of mildly, moderately, and severely decreased eGFR were also found. CONCLUSIONS: MetS was independently associated with an increased risk of decreased eGFR, and individual components of MetS each play a different role in decreased eGFR. Elevated BP may be an important risk factor for the progression of renal dysfunction or even chronic kidney disease.

Prevalence of tobacco related chronic diseases and its role in smoking cessation among smokers in a rural area of Shanghai, China: a cross sectional study.

BACKGROUND: Tobacco smoking is a recognized risk factor for many chronic diseases and previous study evidences have indicated that smokers receive smoking cessation service after the diagnosis of chronic diseases increases successful rate in quitting. But the prevalence of tobacco related chronic diseases (TCD) among smokers, as well as the role of TCD diagnosis in smoking cessation is still unclear in China. METHODS: From June 2016 to December 2017, we sampled 36, 698 residents aged over 18 years by a three stage sampling in Songjiang district, Shanghai. We conducted a cross-sectional study to understand the prevalence of TCD among smokers, and the role of TCD diagnosis in smoking cessation among ex-smokers as well as the smoking cessation attempt among current smokers. RESULTS: Over all, the prevalence of current smoking is 19.78% (48.36% for male and 0.22% for female). 15.93% of smokers have stopped smoking successfully (1, 376/8, 636). The prevalence of ten selected TCDs among smokers range from 0.63% (Chronic Obstructive Pulmonary Disease, COPD) to 36.31% (hypertension). All of 1, 376 ex-smokers had at least one kind of TCD, and 52.33% of them stop smoking after the diagnosis of TCD, the time interval between TCD diagnosis and smoking cessation ranges from 0 to 65 years, with a median of 9 years. Smokers with TCD had higher prevalence of quit smoking, and current smokers with TCD had higher smoking cessation attempt proportion. CONCLUSIONS: The prevalence of current smoking is still very high among male residents in rural area of Shanghai, and the occurrence of TCD even non-lethal one could provide an opportunity for doctors to assist the smoking cessation among smokers.

Mortality rates and the causes of death related to diabetes mellitus in Shanghai Songjiang District: an 11-year retrospective analysis of death certificates.

BACKGROUND: China is one of the countries with the highest prevalence of diabetes in the world. We analysed all the death certificates mentioning diabetes from 2002 to 2012 in Songjiang District of Shanghai to estimate morality rates and examine cause of death patterns. METHODS: Mortality data of 2654 diabetics were collected from the database of local CDC. The data set comprises all causes of death, contributing causes and the underlying cause, thereby the mortality rates of diabetes and its specified complications were analysed. RESULTS: The leading underlying causes of death were various cardiovascular diseases (CVD), which collectively accounted for about 30% of the collected death certificates. Diabetes was determined as the underlying cause of death on 28.7%. The trends in mortality showed that the diabetes related death rate increased about 1.78 fold in the total population during the 11-year period, and the death rate of diabetes and CVD comorbidity increased 2.66 fold. In all the diabetes related deaths, the proportion of people dying of ischaemic heart disease or cerebrovascular disease increased from 18.0% in 2002 to 30.5% in 2012. But the proportions attributed directly to diabetes showed a downtrend, from 46.7-22.0%. CONCLUSIONS: The increasing diabetes related mortality could be chiefly due to the expanding prevalence of CVD, but has nothing to do with diabetes as the underlying cause. Policy makers should pay more attention to primary prevention of diabetes and on the prevention of cardiovascular complications to reduce the burden of diabetes on survival.

Conditional control of gene function by an invertible gene trap in zebrafish.

Conditional mutations are essential for determining the stage- and tissue-specific functions of genes. Here we achieve conditional mutagenesis in zebrafish using FT1, a gene-trap cassette that can be stably inverted by both Cre and Flp recombinases. We demonstrate that intronic insertions in the gene-trapping orientation severely disrupt the expression of the host gene, whereas intronic insertions in the neutral orientation do not significantly affect host gene expression. Cre- and Flp-mediated recombination switches the orientation of the gene-trap cassette, permitting conditional rescue in one orientation and conditional knockout in the other. To illustrate the utility of this system we analyzed the functional consequence of intronic FT1 insertion in supv3l1, a gene encoding a mitochondrial RNA helicase. Global supv311 mutants have impaired mitochondrial function, embryonic lethality, and agenesis of the liver. Conditional rescue of supv311 expression in hepatocytes specifically corrected the liver defects. To test whether the liver function of supv311 is required for viability we used Flp-mediated recombination in the germline to generate a neutral allele at the locus. Subsequently, tissue-specific expression of Cre conditionally inactivated the targeted locus. Hepatocyte-specific inactivation of supv311 caused liver degeneration, growth retardation, and juvenile lethality, a phenotype that was less severe than the global disruption of supv311. Thus, supv311 is required in multiple tissues for organismal viability. Our mutagenesis approach is very efficient and could be used to generate conditional alleles throughout the zebrafish genome. Furthermore, because FT1 is based on the promiscuous Tol2 transposon, it should be applicable to many organisms.

Antitumor effect of fructose 1,6-bisphosphate and its mechanism in hepatocellular carcinoma cells.

We aimed to investigate the antitumor effect and mechanism of fructose 1,6-bisphosphate (F1,6BP) in a hepatocellular carcinoma cell line. HepG2 cells were treated with different concentrations of F1,6BP alone or in combination with antioxidant N-acetyl-L-cysteine (NAC) or catalase (CAT), and cell proliferation assays were performed. Nuclear morphology was observed by fluorescence microscopy after Hoechst staining, and apoptosis was measured with flow cytometry. Changes in reactive oxygen species (ROS) levels in HepG2 cells were detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. A colorimetric assay was adopted to determine the percentage of oxidized glutathione in these cells. CAT and glutathione peroxidase (GSH-Px) mRNA expression levels in HepG2 cells were measured by real-time fluorescence quantitative PCR. HepG2 cell proliferation was significantly inhibited by F1,6BP, accompanied by an increase in intracellular ROS levels and oxidized glutathione. Upregulated apoptosis and characteristic nuclear morphological changes were observed, and the expression of CAT and GSH-Px mRNA was increased after F1,6BP treatment. The antitumor effect of F1,6BP was significantly decreased after pretreatment with NAC and CAT in HepG2 cells. In conclusion, F1,6BP can induce the apoptosis of HepG2 cells. The mechanism involved may be associated with the generation of ROS, especially the production of H2O2.

Tetramethylpyrazine improves oxazolone-induced colitis by inhibiting the NF-κB pathway.

PURPOSE: Tetramethylpyrazine (TMP) is an effective Chinese plant-derived medicine for colitis in the clinic, but the underlying molecular mechanisms of its use remain poorly understood. The purpose of this study was to investigate the mechanisms involved in its therapeutic action. METHODS: A colitis mouse model was induced by oxazolone enema. TMP was administered at 80 mg/kg/day and sulphasalazine (SASP) was used as positive control and administered at 100 mg/kg/day for the treatment of colitis. On the fourth day after enema, mice were sacrificed. The inflammatory response was assessed by the disease activity index and histology. Colon mucosa was isolated and biochemically analyzed. In addition, in vitro studies were performed to evaluate the activity of TMP in Caco-2 cells. RESULTS: Our results showed that TMP improved the colonic inflammatory status as evidenced by histological findings, as well as SASP. These effects were associated with a decrease in nucleus translocation of NF-κB. Paired with this inhibitive activity, there was a decrease in downstream signaling, such as C-MYC, iNOS and COX-2. In vitro assays revealed that TMP inhibited NF-κB translocation and its downstream production of inflammatory factors, such as TNF-α, IL-6 and IL-8, and that ROS production that was induced by LPS in Caco-2 cells. CONCLUSION: TMP improved the colitis induced by oxazoline, and its activity was associated with inhibition of NF-κB translocation, and subsequent inhibition of pro-inflammatory factor production and oxidative stress.

Oleanolic acid induces apoptosis of MKN28 cells via AKT and JNK signaling pathways.

CONTEXT: Oleanolic acid (OA) belongs to the triterpenoid compound group existing widely in food, medicinal herbs and other plants. Its effects on gastric cancer cells and the mechanisms involved have not been investigated. OBJECTIVE: This study aimed to substantiate whether OA induces apoptosis of gastric cancer cell line (MKN28) and to elucidate the molecular mechanism involved. MATERIALS AND METHODS: Cell viability was assessed by MTT assay within the range of 0-160 µg/mL. The effects of OA (5, 10 and 20 µg/mL) on apoptosis of MKN28 cells were evaluated by flow cytometry, DNA fragmentation and mitochondrial membrane potential assays. Western blot and FQRT-PCR assays were used to investigate the mechanism of cell apoptosis induced by OA (5 and 10 µg/mL). RESULTS: OA evidently inhibited cell viability with IC50 of 44.8 and 15.9 µg/mL at 12 and 24 h, respectively. Furthermore, OA increased JNK phosphorylation, decreased AKT phosphorylation, but did not affect p38 and ERK phosphorylation in MKN28 cells. In contrast, OA also significantly enhanced the mRNA expression levels of caspase 3, caspase 9 and Apaf-1 in MKN28 cells. CONCLUSION: OA induces apoptosis of MKN28 cells via the mitochondrial pathway regulated by AKT and JNK signaling pathways.

Treatment Advances in Lung Cancer with Leptomeningeal Metastasis.

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.

Subtype recognition and identification of a prognosis model characterized by antibody-dependent cell phagocytosis-related genes in breast cancer.

BACKGROUND: Breast cancer (BC) is a heterogeneous tumor with a variety of etiology and clinical features. Antibody-dependent cell phagocytosis (ADCP) is the last step of immune checkpoint inhibition (ICI), and macrophages detect and recognize tumor cells, then destroy and engulf tumor cells. Despite the large number, negative regulators that inhibit phagocytic activity are still a key obstacle to the full efficacy of ICI. PATIENTS AND METHODS: An ADCP-related risk score prognostic model for risk stratification as well as prognosis prediction was established in the Cancer Genome Atlas (TCGA) cohort. The predictive value of ADCP risk score in prognosis and immunotherapy was also further validated in the TCGA along with International Cancer Genome Consortium cohorts. To promote the clinical application of the risk score, a nomogram was established, with its effectiveness verified by different methods. RESULTS: In this study, the genes collected from previous studies were defined as ADCP-related genes. In BC patients, two ADCP-related subtypes were identified. The immune characteristics and prognostic stratification were significant different between them. CONCLUSIONS: We identified two subtypes associated with ADCP gene expression in breast cancer. They have significant differences in immune cells, molecular functions, HLA family genes, immune scores, stromal scores, and inflammatory gene expression, which have important guiding significance for the selection of clinical treatment methods. At the same time, we constructed a risk model based on ADCP, and the risk score can be used as a good indicator of prognosis, providing potential therapeutic advantages for chemotherapy and immunotherapy, thus helping the clinical decision-making of BC patients.

Synergistic acceleration of machine learning and molecular docking for prostate-specific antigen ligand design.

Prostate-specific antigen (PSA) serves as a critical biomarker for the early detection and continuous monitoring of prostate cancer. However, commercial PSA detection methods primarily rely on antigen-antibody interactions, leading to issues such as high costs, stringent storage requirements, and potential cross-reactivity due to PSA variant sequence homology. This study is dedicated to the precise design and synthesis of molecular entities tailored for binding with PSA. By employing a million-level virtual screening to obtain potential PSA compounds and effectively guiding the synthesis using machine learning methods, the resulting lead compounds exhibit significantly improved binding affinity compared to those developed before by researchers using high-throughput screening for PSA, substantially reducing screening and development costs. Unlike antibody detection, the design of these small molecules offers promising avenues for advancing prostate cancer diagnostics. Furthermore, this study establishes a systematic framework for the rapid development of customized ligands that precisely target specific protein entities.

The safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in non-small cell lung cancer patients with oncogenic alterations.

Background: The anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunotherapy has been extensively used in patients with non-small cell lung cancer (NSCLC) in which the tumors are negative for oncogenic alterations. However, whether PD-1/PD-L1 blockade therapy could be applicable in patients harboring oncogenic mutations is largely unknown. Methods: In this retrospective study, we analyzed the safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in a NSCLC cohort of 84 patients who harbored oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), k-Ras, RET, HER2 and BRAF. The patients were followed up till disease progression or death. The adverse effects associated with the treatment were carefully evaluated and timely interrupted. Results: There were 50 patients harboring EGFR mutations, 17 patients with k-Ras mutation, 2 patients with ALK rearrangement, 6 patients with RET rearrangement, 6 patients with HER2 exon20 insertion and 3 patients with BRAF V600E mutation. About 58.8% of the k-Ras mutant patients responded to the combinational treatment. The median progression-free survival (mPFS) of the k-Ras cohort was 14 months, with the 12-month median overall survival (mOS) ratio and the 24-month OS ratio of 86.7% and 75.8%, respectively. Patients with EGFR exon21 L858R mutation or RET rearrangement tended to have a more favorable response, while patients harboring ALK rearrangement, HER2 exon20 insertion and BRAF V600E mutation did not respond well to anti-PD-1 inhibitor-based combinational therapy. The incidence of treatment-related toxicity was 52.3% and the most common immune-related adverse events (irAEs) were PD-1 inhibitors-related hypothyroidism and pneumonitis. The PD-L1 status and lung immune prognostic index (LIPI) could be used as biomarkers dictating therapeutic outcomes of the combinational therapy. Conclusions: The anti-PD-1 inhibitor-based combinational therapy elicited exciting anti-tumor efficacy and prolonged patient survival with manageable adverse effects in NSCLC patients harboring oncogenic alterations. The PD-L1 status and LIPI could be used as a biomarker predicting response to anti-PD-1 inhibitor-based combinational treatment in these patients.

[Application of umbilical venous catheter combined with peripherally inserted central catheter in very low birth weight infants].

OBJECTIVE: To study the application of umbilical venous catheter (UVC) combined with peripherally inserted central catheter (PICC) in very low birth weight infants (VLBWIs). METHODS: A retrospective analysis was performed on the VLBWIs in the neonatal intensive care unit who received UVC combined with PICC (catheter group, n=63) or did not receive the catheter treatment (non-catheter group, n=38) to compare the differences in nosocomial infection, weight gain, and length of hospital stay between the two groups. RESULTS: The rate of nosocomial infection was 17% in the catheter group and 24% in the non-catheter group (P>0.05). Compared with the non-catheter group, the catheter group had a significantly higher weight gain (11.7±2.0 g/kg•d vs 10.6±2.3 g/kg•d; P<0.05) and a significantly shorter length of hospital stay (40±11 days vs 45±14 days; P<0.05). There was no significant difference in the incidence of complications between the two groups. CONCLUSIONS: Compared with those not receiving catheter treatment, the VLBWIs receiving UVC combined with PICC have a markedly higher weight gain and a markedly shorter length of hospital stay and show a declining trend in the rate of nosocomial infection.

[High-risk factors for parenteral nutrition-associated cholestasis in very low birth weight infants].

OBJECTIVE: To investigate the high-risk factors for parenteral nutrition-associated cholestasis (PNAC), which is the most common complication of parenteral nutrition for infants, in very low birth weight infants (VLBWIs). METHODS: Retrospective analysis was performed on the clinical and laboratory data of 204 VLBWIs who received parenteral nutrition for over 2 weeks in the neonatal intensive care unit from August 2006 to December 2011. The infants'liver function was evaluated periodically before and after Parenteral nutrition. Univariate analysis and multivariate analysis were performed in the observation (PNAC) and control (without PNAC) groups. RESULTS: PNAC occurred in 46 (22.5%) of the 204 VLBWIs. Univariate analysis showed that continuous positive airway pressure (CPAP) ventilation, respiration failure, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) were significantly increased in the observation group compared with the control group. The observation group had lower birth weights, longer duration of ventilation, later breast feeding beginning, longer duration of fasting, longer duration of parenteral nutrition, and higher cumulated amino acid and lipid emulsion intake. Logistic regression analysis revealed that duration of fasting was a high-risk factor for PNAC (OR=1.115, 95%CI: 1.031-1.207). CONCLUSIONS: Many risk factors are associated with PNAC. Early enteral nutrition and short duration of parenteral nutrition are helpful in preventing the incidence of PNAC in VLBWIs.

A Regression Model to Predict Linezolid Induced Thrombocytopenia in Neonatal Sepsis Patients: A Ten-Year Retrospective Cohort Study.

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

Assessing Individual Risk for High-Risk Early Colorectal Neoplasm for Pre-Selection of Screening in Shanghai, China: A Population-Based Nested Case-Control Study.

OBJECTIVE: To identify people with high-risk early colorectal neoplasm is highly desirable for pre-selection in colorectal cancer (CRC) screening in low-resource countries. We aim to build and validate a risk-based model so as to improve compliance and increase the benefits of screening. PATIENTS AND METHODS: Using data from the Shanghai CRC screening cohort, we conducted a population-based nested case-control study to build a risk-based model. Cases of early colorectal neoplasm were extracted as colorectal adenomas and stage 0-I CRC. Each case was matched with five individuals without neoplasm (controls) by the screening site and year of enrollment. Cases and controls were then randomly divided into two groups, with two thirds for building the risk prediction model and the other one third for model validation. Known risk factors were included for risk prediction models using logistic regressions. The area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow chi-square statistics were used to evaluate model discrimination and calibration. The predicted individual risk probability was calculated under the risk regression equation. RESULTS: The model incorporating age, sex, family history and lifestyle factors including body mass index (BMI), smoking status, alcohol, regular moderate-to-intensity physical activity showed good calibration and discrimination. When the risk cutoff threshold was defined as 17%, the sensitivity and specificity of the model were 63.99% and 53.82%, respectively. The validation data analysis also showed well discrimination. CONCLUSION: A risk prediction model combining personal and lifestyle factors was developed and validated for high-risk early colorectal neoplasm among the Chinese population. This risk-based model could improve the pre-selection for screening and contribute a lot to efficient population-based screening in low-resource countries.

Soy Isoflavones Intake and Obesity in Chinese Adults: A Cross-Sectional Study in Shanghai, China.

This study was designed to examine the association of soy isoflavones (SI) intake with different body measurements indicative of obesity in Chinese adults of Shanghai, a population consuming foods rich in SI. This study used baseline data from the Shanghai Gaofeng cohort study. SI intake was measured by using a self-reported food frequency questionnaire (FFQ). A restricted cubic spline (RCS) was performed to examine the possible nonlinear relationship of SI intake with obesity. A logistic regression model was applied to estimate the odds ratios (OR) and 95% confidence interval (CI). Compared with the lowest tertile group of SI intake, the highest tertile group had a lower prevalence of obesity and central obesity. The OR for overall obesity was 0.91 (95% CI: 0.85, 0.98) in the highest versus the lowest SI tertile group; the associations differed by sex and menopausal status. A negative association was also observed between SI intake and central obesity, and a significant modifying effect of sex was found on the association. No significant interactions were observed between SI intake and physical activity (PA) levels. Our results suggest that Chinese adults with higher dietary intake of SI may be less likely to be obese, particularly for postmenopausal women.