Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Sex differences in the associations between relative fat mass and all-cause and cardiovascular mortality: A population-based prospective cohort study.

BACKGROUND AND AIMS: The novel sex-specific anthropometric equation relative fat mass (RFM) is a new estimator of whole-body fat %. The study aimed to investigate the predictive role of RFM in cardiometabolic abnormalities, cardiovascular disease (CVD), all-cause and cardiovascular mortality, and explored potential sex differences. METHODS AND RESULTS: The study analyzed data from 26,754 adults in NHANES 1999-2010, with a median follow-up of 13.8 years. The correlation between RFM and body composition as well as fat distribution assessed by dual-energy X-ray absorptiometry was investigated. Weighted multivariable generalized linear models, Cox proportional hazards models and restricted cubic spline were applied to investigate the predictive role of RFM in metabolic markers, cardiovascular risk factors, CVD, all-cause and cardiovascular mortality. RFM exhibited a robust correlation with both whole-body fat % and trunk fat %. Higher RFM exhibited a stronger association with impaired glucose homeostasis, serum lipids, the incidence of hypertension, and coronary heart disease in males, while a stronger association with C-reactive protein in females. A U-shaped association between RFM and all-cause mortality was observed only in males. The hazard ratio (HR) of all-cause and cardiovascular mortality in males increased rapidly when RFM exceeded 30. However, in females, the HR of all-cause and cardiovascular mortality fluctuated until RFM exceeded 45, after which it increased rapidly. CONCLUSION: RFM was a sex-specific estimator for both general and central obesity, sex-specific differences in predicting cardiometabolic abnormalities and adverse events using RFM might be partially attributed to differences in body composition and fat distribution between sexes.

Validity of food and nutrient intakes assessed by a food frequency questionnaire among Chinese adults.

BACKGROUND: Studies regarding the validity of the food frequency questionnaire (FFQ) and the food composition table (FCT) are limited in Asian countries. We aimed to evaluate the validity of a 64-item FFQ and different methods of constructing the FFQ FCTs for assessing dietary intakes of foods and nutrients among adults in eastern China. METHODS: A total of 2325 participants (aged 56.2 ± 14.9 years, 51.6% female) from nine cities in Zhejiang province who completed a 64-item FFQ and 3-day 24-hour dietary recalls (24HRs) in 2015 were included. Eight FFQ FCTs were generated covering food items and specific weights estimated using professional knowledge, representative 24HRs data, or the Chinese FCT (CFCT). Energy-adjusted intakes of foods and nutrients were estimated by residual and energy density methods. Spearman correlation coefficients (SCCs) of intakes of 14 food groups and 17 nutrients between FFQ and 24HRs were calculated to evaluate the overall validity of FFQ. RESULTS: The average intakes of most food groups and nutrients assessed with FFQ were higher than those assessed using the 24HRs. For the food groups, the averaged energy-adjusted (residual method) SCC between FFQ and 24HRs was 0.27, ranging from 0.14 (starch-rich beans) to 0.49 (aquatic products). For nutrient assessment, the weighted FCT (WFCT) performs the best, and the averaged energy-adjusted (residual method) SCC was 0.26, ranging from 0.16 (iron) to 0.37 (potassium). Similar correlations with 24HRs were observed when using other FFQ FCT in the calculation of nutrient intakes. CONCLUSION: The 64-item Chinese FFQ and the WFCT were reasonably valid to assess the dietary intakes of certain foods and nutrients among adults in eastern China.

Comprehensively evaluating the relationships between marital status and other family factors with cardiovascular disease and long-term overall mortality in the elderly: a study of 48 510 Chinese individuals.

BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.

Structure Reveals the Impact of Surface Charge Distribution on the Phase Separation and Aggregation of Slr0280.

Liquid-liquid phase separation (LLPS) plays a key role in the regulation of life activities. Here, we reported a protein from Synechocystis sp. PCC 6803 and annotated as Slr0280. To obtain a water-soluble protein, we deleted the N-terminus transmembrane domain and named it Slr0280Δ. Slr0280Δ with high concentration can undergo LLPS at a low temperature in vitro. It belongs to the phosphodiester glycosidase family of proteins and has a segment of a low-complexity sequence region (LCR), which is thought to regulate the LLPS. Our results show that electrostatic interactions impact the LLPS of Slr0280Δ. We also acquired the structure of Slr0280Δ, which has many grooves on the surface with a large distribution of positive and negative charges. This may be advantageous for the LLPS of Slr0280Δ through electrostatic interactions. Furthermore, the conserved amino acid (arginine at position 531) located on the LCR is important for maintaining the stability of Slr0280Δ as well as LLPS. Our research indicated that the LLPS of proteins can be transformed into aggregation by changing the surface charge distribution.

Two-stage equalization for ultra-fast RSOP and inter symbol interference compensation based on a simplified Kalman filter.

We propose a two-stage equalization based on a simplified Kalman filter, which is used to solve the rapid rotation of the state of polarization (RSOP) that is caused by lightning strikes on optical cables and the extra inter symbol interference (ISI) introduced in the system. By analyzing the special expression of matrix coefficient in the Kalman filter under polarization demultiplexing, the simplified idea of a Kalman filter is provided, and its updating process is transformed into a kind of multiple-input-multiple-output (MIMO) structure algorithm. At the same time, the second stage finite impulse response filter is used to solve the ISI that is difficult to be solved by a Kalman filter. The performance of the proposed algorithm was tested in a coherent system of 28Gbaud PDM-QPSK/16QAM. The results confirm that on the basis of lower complexity than a Kalman filter, the proposed algorithm reduces its complexity by more than 30% compared to traditional MIMO equalization algorithm under the premise of linear operation, and which also can handle RSOP of 20 Mrad/s. When the system suffers from the extra ISI due to the limited device bandwidth, the optical signal to noise ratio of the proposed algorithm is about 4 dB lower than the Kalman filter at the same bit error rate.

Association of the number of natural teeth with dietary diversity and nutritional status in older adults: A cross-sectional study in China.

AIM: To investigate the association of the number of natural teeth with overall dietary diversity and nutritional status in a nationally representative study among older adults in China. MATERIALS AND METHODS: A cross-sectional analysis was conducted among community-dwelling adults aged 65 years or older from the Chinese Longitudinal Healthy Longevity Study. According to the self-reported number of natural teeth, participants were categorized into ≥20, 10-19, 1-9 natural teeth, and edentulous. Dietary diversity score (DDS) was constructed based on intake frequencies of 10 food groups assessed by a simplified food frequency questionnaire. The geriatric nutritional risk index was used to measure the malnutrition status (i.e., normal, mild malnutrition, and moderate-to-severe malnutrition) among a subgroup of participants. Linear and multinomial logistic regression models were used to examine the corresponding associations. RESULTS: Among 54,796 study participants, the mean (SD) age was 87.86 (11.45) years, 82.7% had poor dentition (<20 natural teeth), and 27.3% wore dentures. After multivariable adjustment, participants with poor dentition had lower DDSs (ßedentulous  = -0.39, 95% confidence interval [CI], -0.48, -0.30; ß1-9 teeth  = -0.46, 95% CI, -0.55, -0.37; ß10-19 teeth  = -0.36, 95% CI, -0.46, -0.26) than those with 20 natural teeth or more. For individual food items, edentulous, 1-9 and 10-19 natural teeth were associated with lower odds of regular intake of fresh fruits, fresh vegetables, meat, fish and aquatic products, eggs, legumes, preserved vegetables, tea, and garlic, but higher odds of regular intake of sugar and sweets. Among participants with poor dentition, individuals without dentures had lower intake frequencies of most food groups than those wearing dentures. In addition, poor dentition was related to lower odds of normal nutritional status (odds ratio = 0.49, 95% CI, 0.27, 0.89). CONCLUSIONS: Older adults with poor dentition had significantly lower dietary diversity and worse nutritional status. Future studies are warranted to identify effective interventions to improve the dietary quality and nutrition status among partially and fully edentulous individuals, including those with Stage IV periodontitis.

Prevalence and prognostic importance of malnutrition, as assessed by four different scoring systems, in elder patients with heart failure.

BACKGROUND AND AIMS: The lack of standard diagnostic criteria in elder patients with heart failure (HF) makes it challenging to diagnose and manage malnutrition. We aimed to explore the prevalence of malnutrition, its associations and prognostic significance among elder patients with HF using four different nutritional scoring systems. METHODS AND RESULTS: Consecutively presenting patients aged ⩾65 years, diagnosed with HF, and admitted to HF care unit of Fuwai Hospital CAMS&PUMC (Beijing, China) were assessed for nutritional indices. In total, 1371 patients were enrolled (59.4% men; mean age 72 years; median NT-proBNP 2343 ng/L). Using scores for the prognostic nutritional index (PNI) ≤38, controlling nutritional status (CONUT) score >4, geriatric nutritional risk index (GNRI) ≤91, and triglycerides, total cholesterol, and body weight index (TCBI) ≤1109, 10.4%, 18.3%, 9.2%, and 50.0% of patients had moderate or severe malnutrition, respectively. There was a strong association between worse scores and lower body mass index, more severe symptoms, atrial fibrillation, and anemia. The mortality over a median follow-up of 962 days (interquartile range (IQR): 903-1029 days) was 28.3% (n = 388). For those with moderate or severe condition, 1-year mortality was 35.2% for PNI, 28.3% for CONUT, 28.0% for GNRI, and 19.1% for TCBI. Malnutrition, defined by any of the included indices, showed added prognostic value when incorporated into a model and included preexisting prognostic factors (C-statistic: 0.711). However, defining malnutrition by the CONUT score yielded the most significant improvement in the prognostic predictive value (C-statistic: 0.721; p < 0.001). CONCLUSION: Malnutrition is prevalent among elder patients with HF and confers increased mortality risk. Among the nutritional scores studied, the CONUT score was most effective in predicting the mortality risk. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov; Unique Identifier: NCT02664818.

Successful pregnancy in a female with embryonal rhabdomyosarcoma of the cervix who received biopsy and chemotherapy alone without recurrence after 16 years: a case report and literature review.

BACKGROUND: Embryonal rhabdomyosarcoma (ERMS) of the uterine cervix is rare, but the population affected is mostly underage females. The scope of surgery has now evolved from extensive to limited, and organ-preserving surgery combined with chemotherapy is recommended to preserve the patient's fertility. However, reports of birth outcomes are rare. CASE: A minor woman with cervical ERMS who underwent only an outpatient biopsy of the lesion had no residual lesion on subsequent multipoint cervical biopsy and refused radical surgery or cervical conization, after which the patient received a nonclassical regimen of chemotherapy. The patient stopped the chemotherapy on her own, but the patient conceived spontaneously 16 years later with a good pregnancy outcome and no recurrence. CONCLUSIONS: This case suggests that preservation of reproductive function is often feasible in immature women with cervical ERMS, and the prognosis is usually good as long as the primary tumour can be surgically removed and the lesion is free of residual disease. We also look forward to reports of subsequent growth and pregnancy outcomes in other children with reproductive tract RMS. In cervical ERMS, accurate evaluation of the disease and development of an individualized treatment plan are crucial, and the protection of reproductive function and psychological well-being deserves special attention.

Multimorbidity burden and developmental trajectory in relation to later-life dementia: A prospective study.

INTRODUCTION: This study assessed the associations of multimorbidity burden and its developmental trajectory with later-life dementia. METHODS: Among 5923 Health and Retirement Study participants, major chronic conditions including hypertension, diabetes mellitus, cancer, lung diseases, heart disease, stroke, psychological disorders, and arthritis were self- or proxy-reported in 1994-2008. Dementia diagnosis was self- or proxy-reported in 2008-2018. We used Cox regression to assess the associations of multimorbidity with incident dementia. RESULTS: During follow-up (median = 8 years), 701 participants developed dementia. Each additional chronic condition in 2008 was related to 15% (confidence interval: 9% to 22%) higher hazard of dementia. Multimorbidity trajectories in 1994-2008 were classified as "rapid growth", "steady growth", "slow growth", and "no new condition" by the group-based trajectory modelling methods. Compared to "no new condition", the "rapid growth" trajectory was related to 32% (3% to 69%) higher dementia risk. CONCLUSIONS: Both multimorbidity burden and its developmental trajectory were prospectively associated with risk of dementia.

Meta-analysis of arbidol versus lopinavir/ritonavir in the treatment of coronavirus disease 2019.

OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.

Regulator of calcineurin 1 is a novel RNA-binding protein to regulate neuronal apoptosis.

Posttranscriptional regulation of gene expression plays an important role in the maturation, transport, stability and translation of coding and noncoding RNAs. RNA-binding protein (RBP) is a key factor of the regulation. Regulator of calcineurin 1 (RCAN1) is a multifunctional protein involved in neurodegeneration, mitochondrial dysfunction, inflammation and protein glycosylation, and plays an important role in the pathogenesis of Down syndrome and Alzheimer's disease. In this report, we discovered that RCNA1 is a novel RNA-binding protein. A 23 nucleotide sequence of adenine nucleotide translocator (ANT1) mRNA was identified as the binding motif of RCAN1. Furthermore, we found that R1SR13, as the RNA aptamer of RCAN1 identified by SELEX, blocked RCAN1-induced inhibition of the nuclear factor of activated T cells (NFAT) and NF-κB signaling pathways, and reduced neuronal apoptosis. Taken together, our results demonstrate that RCAN1 is a novel RNA-binding protein and the RNA aptamer of RCAN1 plays a neuroprotective role.

Does a long interval between neoadjuvant chemoradiotherapy and surgery benefit the clinical outcomes of locally advanced rectal cancer? A systematic review and meta analyses.

PURPOSE: The study aims to systematically evaluate the clinical efficacy after 8 weeks (long interval, LI) between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer. METHODS: The PubMed database, EMBASE database, and the Cochrane Library (deadline: September 25, 2021) were searched to select clinical studies that compared two intervals between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: after 8 weeks (long interval, LI) and within 8 weeks (short interval, SI). The included studies were screened and evaluated according to the inclusion and exclusion criteria, and meta-analysis was performed by RevMan 5.3 software. RESULTS: Eighteen studies were included, with 9070 cases in the LI group and 14,207 cases in the SI group. The analysis results showed that the pathologic complete response (PCR) rate in the LI group was higher than that in the SI group (P < 0.00001). There was no significant difference in the R0 resection rate (P = 0.85), anal preservation rate (P = 0.89), morbidity rate (P = 0.60), anastomotic leakage rate (P = 0.06), operation time (P = 0.58), local recurrence rate (P = 0.56), distant metastasis rate (P = 0.32), or overall survival (OS) rate (P = 0.17) between the two groups. CONCLUSION: A longer interval between neoadjuvant chemoradiotherapy and surgery can improve the PCR rate; however, it has no significant impact on the clinical efficacy or long-term prognosis. Due to some limitations in the number and quality of the studies, these findings still need to be further verified by multicenter, large-sample high-quality RCTs in the future.

Prognostic utility of the prognostic nutritional index combined with serum sodium level in patients with heart failure.

BACKGROUND AND AIMS: Both malnutrition and hyponatremia (serum sodium <135 mmol/L) can be induced by the impaired absorption function of the edematous intestinal wall caused by heart failure (HF) and are prognostic factors of mortality in HF. However, little is known about the interrelationship of nutritional status and hyponatremia in mortality risk prediction in HF. METHODS AND RESULTS: This study enrolled 2882 HF patients admitted to the HF care unit of Fuwai Hospital, Beijing, China from 2008 to 2018; 71.3% were male and the mean age was 56.64 ± 15.96 years. Nutritional status was assessed by prognostic nutritional index (PNI), calculated as serum albumin (g/L) + 5 × total lymphocyte count (109/L). Lower PNI indicates worse nutritional status. Patients were divided into 8 groups based on baseline PNI quartiles (Q1: <43.6, Q2: 43.6-48.55, Q3: 48.55-63.25, Q4: >63.25) and sodium level (normal sodium and hyponatremia). After adjustment, patients in the PNI Q1 associated with hyponatremia had a 2.12-fold higher risk of all-cause death (95% confidence interval [CI]: 1.67-2.70) compared with those in the PNI Q4 with normal sodium. A refinement in risk prediction was observed after adding PNI quartile and serum sodium category to the original model (ΔC-statistic = 0.018, 95% CI: 0.007-0.025; net re-classification index = 0.459, 95% CI: 0.371-0.548; integrated discrimination improvement = 0.025, 95% CI: 0.018-0.032). CONCLUSION: HF patients with both the lowest PNI quartile and hyponatremia are at higher risk of all-cause mortality. The combination of PNI and serum sodium level enhanced the predictive value for all-cause mortality in hospitalized HF patients. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov; Unique Identifier: NCT02664818.

Hydrogen Bond Organic Frameworks as a Novel Electrochemiluminescence Luminophore: Simple Synthesis and Ultrasensitive Biosensing.

Nowadays, continuous efforts have been devoted to searching highly efficient electrochemiluminescence (ECL) emitters for applications in clinical diagnosis and food safety. In this work, triazinyl-based hydrogen bond organic frameworks (Tr-HOFs) were synthesized by N···H hydrogen bond self-assembly aggregation, where 6,6'-(1,4-phenylene)bis(1,3,5-triazine-2,4-diamine) (phenyDAT) was prepared via the cyclization reaction and behaved as a novel ligand. Impressively, the resulting Tr-HOFs showed strong ECL responses with highly enhanced ECL efficiency (21.3%) relative to the Ru(bpy)32+ standard, while phenyDAT hardly showed any ECL emission in aqueous phase. The Tr-HOFs innovatively worked as a new ECL luminophore to construct a label-free biosensor for assay of kanamycin (Kana). Specifically, the ECL response greatly weakened upon assembly of captured DNA with ferrocene (cDNA-Fc) onto the Tr-HOFs-modified electrode, while the ECL signals were adversely recovered by releasing linked DNA (L-DNA) from double-stranded DNA (dsDNA, hybridization of aptamer DNA (aptDNA) with L-DNA) due to the specific recognition of Kana with the aptDNA combined by the linkage of L-DNA and cDNA-Fc on the electrode. The as-built sensor showed a broadened linear range (1 nM-10 µM) and a limit of detection (LOD) down to 0.28 nM, which also displayed satisfactory results in the analysis of Kana in the milk and diluted human serum samples. This work offers a novel pathway to design an ECL emitter with organic molecules, holding great promise in biomedical analysis and food detection.

The electrochemiluminescence coreactant accelerator of metal-organic frameworks grafted with N-(aminobutyl)-N-(ethylisoluminol) for the ultrasensitive detection of chloramphenicol.

In this work, metal-organic frameworks (MOFs) are utilized as effective ECL coreactant accelerator to enhance the ECL responses of N-(aminobutyl)-N-(ethylisoluminol) (ABEI). Zn-based MOFs (MOF-Zn-1) were prepared by chelating Zn ions with melamine and thiophenedicarboxylic acid (TPDA), which observably accelerated the electrocatalytic oxidation of tripropylamine (TPA). Then, ABEI-MOF-Zn-1 as a high-performance ECL emitter was synthesized via an amide reaction between ABEI and mercaptopropionic acid (MPA) modified MOF-Zn-1. Strikingly, the ABEI-MOF-Zn-1 showed the 18-fold increase in the ECL signals relative to pure ABEI by using TPA as a coreactant. Moreover, ferrocene (Fc) as a quencher was first linked with capture DNA (cDNA), and then used to modify the ABEI-MOF-Zn-1, thereby constructing a label-free ECL biosensor. After the linkage between chloramphenicol (CAP) and aptamer DNA (aptDNA), the ECL response was definitely recovered by releasing L-DNA from double-stranded DNA (dsDNA, hybridization of aptDNA and L-DNA). The resultant sensor showed a wide linear range of 1.00 nM-0.10 mM (R2 = 0.99) and a low limit of detection (LOD) down to 0.11 nM for detecting CAP. This work developed a novel pattern to design an efficient ECL enhanced emitter, coupled by expanding its potential applications in clinical diagnosis.

Development and validation of nomograms for epithelial ovarian cancer: a SEER population-based, real-world study.

Aim: To develop and internally validate nomograms to predict the overall survival (OS) and the cancer-specific survival (CSS) of patients with epithelial ovarian cancer (EOC). Methods: A total of 9001 EOC patients diagnosed between 2010 and 2013 were randomly divided into the training (n = 6301) and validation (n = 2700) cohorts. Nomogram and bootstrap validation were used to assess the predictive values of the models, including discrimination, calibration and clinical benefit. Results: In the validation cohort, the concordance statistic values were 0.733 for OS and 0.747 for CSS. Calibration plots and decision curve analyses demonstrated moderate accuracy and clinical applicability. Conclusion: Nomograms were user-friendly tools for guiding clinical treatment and estimating prognosis.

Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics.

Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.

A novel cysteine-sparing G73A mutation of NOTCH3 in a Chinese CADASIL family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disease leading to stroke and vascular dementia. CADASIL is an inherited small blood vessel disease caused by mutations in the gene encoding the neurogenic locus notch homolog protein 3 (NOTCH3). NOTCH3 is large type I membrane receptor mainly expressed in vascular smooth muscle cells and pericytes. Most identified mutations result in insert or deletion of a cysteine residue within the EGF-like repeats. To date, some cases with a cysteine-sparing mutant have been described. Genetic analysis revealed a novel mutation in NOTCH3 in a CADASIL family. Molecular analysis revealed its potential pathogenic mechanism in causing CADASIL. In this paper, we present a Chinese family with a novel cysteine-sparing mutation in exon 3 (c.218G>C, p.G73A) of the NOTCH3 gene. Family carriers of the same mutation presented with symptoms and imaging abnormalities characteristic of CADASIL. The location of glycine 73 in between C5-C6 disulfide bond of EGF-like domain 1 shows high conservation from humans to zebra fish. It has previously been suggested that the aggregate-prone property of mutant NOTCH3 contributes to a cytotoxic effect in the pathogenic mechanism underlying CADASIL. Here, we investigated the pathogenic mechanism of the new mutation in vitro using HEK293 cells transfected with either a wild-type (WT) or c.218G>C (p.G73A) NOTCH3ECD plasmids, and we found p.G73A NOTCH3ECD was more prone to form aggregation and resistant to degradation. Moreover, the p.G73A NOTCH3ECD compromised cell viability by promoting apoptosis. Two known CADASIL mutants R133C and R75P showed similar results with G73A mutants. Our study here identified G73A as a new mutation in NOTCH3 to cause CADASIL and revealed that the G73A mutation and two known mutants R75P and R133C decreased NOTCH3 protein turnover and induced cell death.

Calculating the overall survival probability in patients with cervical cancer: a nomogram and decision curve analysis-based study.

BACKGROUND: Cervical cancer has long been a common malignance troubling women. However, there are few studies developing nomogram with comprehensive factors for the prognosis of cervical cancer. Hence, we aimed to build a nomogram to calculate the overall survival (OS) probability in patients with cervical cancer. METHODS: Data of 9876 female patients in SEER database and diagnosed as cervical cancer during 2010-2015, was retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression model were applied to select predicted factors and a nomogram was developed to visualize the prediction model. The nomogram was compared with the FIGO stage prediction model. Harrell's C-index, receiver operating curve, calibration plot and decision curve analysis were used to assess the discrimination, accuracy, calibration and clinical utility of the prediction models. RESULT: Eleven independent prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, primary site surgery, regional lymph node surgery, radiotherapy and chemotherapy, were used to build the nomogram. The C-index of the nomogram was 0.826 (95% CI: 0.818 to 0.834), which was better than that of the FIGO stage prediction model (C-index: 0.785, 95% CI: 0.776 to 0.793). Calibration plot of the nomogram was well fitted in 3-year overall OS prediction, but overfitting in 5-year OS prediction. The net benefit of the nomogram was higher than the FIGO prediction model. CONCLUSION: A clinical useful nomogram for calculating the overall survival probability in cervical cancer patients was developed. It performed better than the FIGO stage prediction model and could help clinicians to choose optimal treatments and precisely predict prognosis in clinical care and research.