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Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Patients with early-stage TNBCs have distinct likelihood of distant recurrence. Current therapeutic guidance is still limited.Methods: We extracted transcriptome data for 189 pathologically confirmed pT1-2N0M0 TNBC patients at Fudan University Shanghai Cancer Center. Candidate mRNAs were filtered, which was followed by differential expressed mRNAs analysis, survival analysis, and LASSO Cox regression model. All-subsets regression program was used for constructing a multi-mRNA signature in the training set (n=159); the accuracy and prognostic value were then validated using an independent validation set (n=158). Results: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues. Early-stage TNBCs are featured of basal-like and immune-suppressed subtype and homologous recombination ability deficiency. We developed a prognostic signature contained seven mRNAs from transcriptome data (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2). In both the training (n=159) and validation cohorts (n=158), the signature could identify patients with relatively high recurrence risks and serve as an independent prognostic factor. The signature had better prognostic value than traditional clinicopathological features in both sets. Among the seven mRNAs, TMEM101 is highly expressed in TNBC and represents a potential therapeutic target. Inhibition of TMEM101 impaired tumor progression.Conclusions: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. Clinical and genomic low risk TNBC patients may have the opportunity to avoid adjuvant chemotherapy

Background An early indicator for monitoring the effect of adjuvant treatment after lung cancer surgery is urgently needed. The study was to explore the effects of epithelial cell adhesion molecule (EpCAM) of circulating tumor cells (CTCs) in NSCLC patients with postoperative adjuvant chemotherapy. Methods Two drugs (platinum-containing chemotherapeutics + platinum-free chemotherapeutics) first-line chemotherapy regimen were given after surgery. MRNA of EpCAM was detected. Chest computed tomography, head computed tomography and abdominal B-ultrasound were reviewed before the first and third chemotherapy. Results EpCAM in CTCs from peripheral blood between the recurrent group and the non-recurrent group at 1 day before surgery, first, second and third adjuvant chemotherapy were no significant differences (P>0.05). Only one day before the fourth adjuvant chemotherapy treatment, it showed significant difference between the recurrent group and the non-recurrent group (P=0.008). There was a significant difference between the time of imaging diagnosis of recurrence or metastasis and the time of monitoring the expression level of EpCAM in CTCs from peripheral blood (P

BACKGROUND Previous studies indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relationship between circulating selenium and risk of first stroke remains inconclusive. OBJECTIVE We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. METHODS In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. RESULTS During a median follow-up duration of 4.5 years (IQR, 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline (≥ 7.7 (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, versus

Patients with Zellweger spectrum disorder (ZSD) commonly present with vision loss due to mutations in PEX genes required for peroxisome assembly and function. Here, we evaluate PEX1 retinal gene augmentation therapy in a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) of the most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.HsPEX1.HA) and control AAV8.CMV.EGFP vectors were administered by subretinal injection in contralateral eyes of early (5-week-old)- or later (9-week-old)-stage retinopathy cohorts. HsPEX1.HA protein was expressed in the retina with no gross histologic side effects. Peroxisomal metabolic functions, assessed by retinal C26:0 lysophosphatidylcholine (lyso-PC) levels, were partially normalized after therapeutic vector treatment. Full-field flash electroretinogram (ffERG) analyses at 8 weeks post-injection showed a 2-fold improved retinal response in the therapeutic relative to control vector-injected eyes. ffERG improved by 1.6- to 2.5-fold in the therapeutic vector-injected eyes when each cohort reached 25 weeks of age. At 32 weeks of age, the average ffERG response was double in the therapeutic relative to control vector-injected eyes in both cohorts. Optomotor reflex analyses trended toward improvement. These proof-of-concept studies represent the first application of gene augmentation therapy to treat peroxisome biogenesis disorders and support the potential for retinal gene delivery to improve vision in these patients.

Little information is available on the association between brachial-ankle pulse wave velocity (baPWV) and the risk of stroke in Chinese H-type hypertension patients. Therefore, our study aimed to assess this association between baseline baPWV and short-term risk of first stroke and to propose a cutoff value of baPWV that could predict near cerebrovascular events. A total of 9787 hypertension patients without preexisting stroke who underwent baPWV measurement were included. The primary end points were first symptomatic stroke. Secondary end points were first ischemic stroke and first hemorrhagic stroke. During a median follow-up of 20.8 months, there was a total of 138 first strokes including 123 first ischemic strokes and 15 first hemorrhagic strokes. When baPWV was categorized in quartiles, the higher risks of first stroke (HR = 1.52; 95% CI: 1.05-2.21) and first ischemic stroke (HR = 1.53; 95% CI: 1.03-2.26) were found in participants in quartile 4 (≥21.31 m/s), compared with those in quartile 1-3 (

We aimed to evaluate the relationship of plasma 25-hydroxyvitamin D3 (25[OH]D3) with the risk of new-onset proteinuria and examine the possible effect modifiers in patients with hypertension and without chronic kidney disease at baseline.This is a post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial. A total of 1655 patients with hypertension, who had plasma 25(OH)D3 measurements, as well as without proteinuria and with an estimated glomerular filtration rate of ≥60 mL/min/1.73 mThe mean (standard deviation) 25(OH)D3 level at baseline was 18.6 (7.5) ng/mL. The median follow-up duration was 4.4 years. Overall, there was a significant inverse association between plasma 25(OH)D3 and the risk of new-onset proteinuria (per standard deviation increment; [odds ratio] OR: 0.70; 95% confidence interval [CI]: 0.50, 0.97). Accordingly, when 25(OH)D3 was assessed as quartiles, a significantly lower risk of new-onset proteinuria was found in participants in quartiles 3-4 (≥17.8 ng/mL; OR: 0.45; 95% CI: 0.23, 0.87), compared with those in quartile 1 (13.1 ng/mL). Furthermore, a stronger inverse relationship of plasma 25(OH)D3 and new-onset proteinuria was observed in nondiabetic participants (per standard deviation increment; OR: 0.57; 95% CI: 0.39, 0.83; vs. diabetics: OR: 1.48; 95% CI: 0.67, 3.28; P for interaction = 0.028).There was a significant inverse association between plasma 25(OH)D3 and the risk of proteinuria in patients with hypertension, especially in those without diabetes.

BackgroundThe purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors.MethodsWe conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25–64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings.Results393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1–Q3: ConclusionsHigh fasting blood glucose may be significantly associated with risk of new-onset hypertension in Chinese women, especially in women with higher total cholesterol. Further randomized studies are needed to confirm our findings.

AIM The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p

OBJECTIVE We aimed to investigate the prospective association between self-perceived psychological stress and first stroke, and examine possible effect modifiers among adults with hypertension. METHODS A total of 20,688 hypertensive adults with information on self-perceived psychological stress at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). Participants were randomly assigned to a double-blind treatment of receiving a single tablet daily with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. Follow up visits occurred every 3 months after randomization. Psychological stress was measured with a one-item 3-point rating scale. The primary outcome was first stroke (fatal or nonfatal). RESULTS The median treatment period was 4.5 years. Compared with participants with low levels of psychological stress, those with high psychological stress had a significantly higher risk of first stroke (adjusted HR, 1.40; 95%CI: 1.01, 1.94) or first ischemic stroke (adjusted HR, 1.45; 95%CI: 1.01, 2.09). Moreover, a stronger positive relationship between psychological stress and first stroke was found in participants with time-averaged mean arterial pressure (MAP)

Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. Of 112 patients, median age at T-VEC initiation was 69 years (range 21–93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.

The current study aimed to explore the association between carotid intima-media thickness (CIMT) and cognitive function assessed by the Mini-Mental State Examination (MMSE) and to examine possible effect modifiers in hypertensive patients. A total of 14,322 hypertensive participants (mean age 64.2 ± 7.4 years; 40.9% male) from the China Stroke Primary Prevention Trial (CSPPT) were included in the final analysis. CIMT was measured by ultrasound, and data were collected at the last follow-up visit; MMSE was used to evaluate cognitive function. Nonparametric smoothing plots, multivariate linear regression analysis, subgroup analyses and interaction testing were performed to examine the relationship between the CIMI and cognitive function and effect modification. The mean CIMT was 0.74 ± 0.11 mm, and the mean MMSE score was 23.5 ± 4.8. There was a significant interaction (P interaction < 0.05) in both male and female populations stratified by age (

Online teaching has both opportunities and challenges. The main issues that are emphasized in this study is on how to grasp and adapt to the situation, strengthen training and policy incentives, establish quality assurance supervision and inspection as well as linkage mechanism, and actively explore the reform mode. From the perspective of management, taking Baoshan University in Yunnan Province as an example, this article summarizes the practical experience of online teaching, analyzes the shortcomings of online teaching, explores the online and offline hybrid teaching, and promotes local colleges to reform their teaching mode.

● Our retrospective cohort study aimed to elucidate which factors (nasal surgery: septoplasty or functional endoscopic sinus surgery (FESS), palate surgery: uvulopalatal flap (UPF) or palatal muscle resection (PMR)), demography, polysomnography, Friedman stage, drug-induced sleep endoscopy (DISE) results) influence the success of surgery in patients who had been operated to treat obstructive sleep apnea (OSA). ● We used seven machine learning (ML) models (logistic regression-based models (lasso, elastic net (EN), ridge), tree-based models (bagging, random forest (RF), support vector machine (SVM), and neural networks (NN)). ● Among the seven models, their performances were first ranked by the area under the receiver operating characteristic curve (AUC): lasso (0.8317), EN (0.7500), SVM (0.7163), bagging (0.7115), random forest (0.7115), NN (0.6923) and ridge (0.6538), which shows that lasso had the best performance. ● Tonsil grade and Nasopharynx Oropharynx Hypopharynx and Larynx (NOHL) classification of the epiglottis in DISE were selected as the most important variables in all models including lasso. ● Through the novel ML technique, the surgical success rate of OSA is ultimately dependent on tonsil grade and NOHL classification of the epiglottis in DISE regardless of the type of nasal or palate surgery.

Coronavirus disease 2019 (COVID-19), an acute infectious disease, which is characterized by influenza, fever, cough and dyspnea. Up to now, the pathogenic mechanism and radical cure treatment for COVID-19 are still unknown. However, COVID-19 could lead to pneumonia, multiple organ failure and even death with disease development. During the period of February 10 and March 26, 2020, we admitted and treated three COVID-19 patients complicated with acute myocardial infarction. As we all know, acute myocardial infarction is a kind of disease that induces myocardial ischemia necrosis and leads to high mortality. Through the three COVID-19 patients complicated with acute myocardial infarction, we have strengthened our nursing experience. Thus, we wish to share our nursing experience with these cases by analyzing the etiology of three patients with coronavirus disease 2019 (COVID-19) complicated with acute myocardial infarction in this paper. First, we retrospectively analyzed the clinical data, including patient complaints, diagnosis, treatment, and prognosis, of three patients with COVID-19 complicated with acute myocardial infarction admitted to Ward II, Department of Infectious Diseases III, Huoshenshan Hospital, Wuhan, Hubei Province, China, between February 10 and March 26, 2020. Then, we searched for relevant literature, analyzed etiology, and summarized the nursing measures taken. For COVID-19 patients with a high risk of acute myocardial infarction, nurses should stay vigilant, closely monitor any change in condition, and implement early measures to maintain vital signs and enable timely visits with specialists. Finally, we importantly found that these nursing measures are keys to managing the patient's condition, improving patient outcomes, and increasing the chance of treatment success.

Background The Affordable Care Act's Medicaid expansion is associated with earlier diagnosis and improved care among lower socioeconomic status populations with cancer, but its impact on melanoma is undefined. Objective To determine the association of Medicaid expansion with stage of diagnosis and use of sentinel lymph node biopsy in nonelderly adult patients with newly diagnosed clinically localized melanoma. Methods Quasi-experimental, difference-in-differences retrospective cohort analysis using data from the National Cancer Database from 2010 to 2017. Patients from expansion versus nonexpansion states and diagnosed before (2010-2013) versus after (2014-2017) expansion were identified. Results Of 83,322 patients, 46.6% were female, and the median age was 55 years (interquartile range, 49-60). After risk adjustment, Medicaid expansion was associated with a decrease in the diagnosis of T1b stage or higher melanoma (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.88-0.98; P = .011) and decrease in uninsured status (OR, 0.61; 95% CI, 0.52-0.72; P Limitations Retrospective study using a national database. Conclusion In this study of patients with clinically localized melanoma, Medicaid expansion was associated with a decrease in the diagnosis of later T-stage tumors.

A variety of microRNAs (miRNAs) are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, the role of miR‐10a‐5p in the progression of HCC remains unclear. Therefore, the purpose of this study was to determine the role of miR‐10a‐5p in the development of HCC and the possible molecular mechanism. miR‐10a‐5p expression in HCC tissues and plasma from patients was detected by quantitative real‐time polymerase chain reaction. Migratory changes in HCC cells were detected after the overexpression of miR‐10a‐5p. Epithelial–mesenchymal transition (EMT)‐related proteins were detected by Western blot. Finally, through luciferase assay and rescue experiments, the mechanism by which miR‐10a‐5p regulates its downstream gene, human spindle and kinetochore‐associated complex subunit 1, SKA1 and the interaction between these molecules in the development of HCC were determined. The expression of miR‐10a‐5p was markedly downregulated in HCC tissues, cell lines, and plasma. The overexpression of miR‐10a‐5p significantly inhibited the migration, invasion, and EMT of HCC cells. Furthermore, SKA1 was shown to be a downstream gene of miR‐10a‐5p. SKA1 silencing had the same effect as miR‐10a‐5p overexpression in HCC. In particular, the overexpression of SKA1 reversed the inhibitory effects of miR‐10a‐5p in HCC. Taken together, low miR‐10a‐5p expression is associated with HCC progression. miR‐10a‐5p inhibits the malignant development of HCC by negatively regulating SKA1.

Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults. A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose 0.05). Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components. Level III, a well-designed cohort.

Preoperative biopsy (PBx) is often recommended for retroperitoneal sarcoma (RPS), but its utilization rate and impact on perioperative management and outcomes remains undefined. Using the National Cancer Database, patients who underwent resection of non-metastatic RPS were identified (2006–2014). Patients who did and did not undergo PBx of the primary tumor were compared using propensity matching, and factors associated with survival were assessed by multivariable analysis. Of 2620 patients, 1110 (42.4%) underwent PBx. Factors significantly associated with performance of PBx included male sex [odds ratio (OR) 1.2, P = 0.035], tumor size ≤ 5 cm (OR 1.5, P = 0.012), tumor size > 5 to ≤ 10 cm (OR 1.3, P = 0.009), non-well-differentiated liposarcoma histology (OR 2.0, P ≤ 0.001), and treatment at a high-volume center (OR 1.3, P = 0.021). Receipt of PBx was significantly associated with administration of neoadjuvant radiation (OR 8.8, P < 0.001) or systemic therapy (OR 3.3, P < 0.001), radical surgical resection (OR 1.6, P < 0.001), and complete tumor resection (OR 1.5, P < 0.003). Neoadjuvant radiation [hazard ratio (HR) 0.7, P = 0.003] and complete tumor resection (HR 0.6, P < 0.001) were significantly associated with improved overall survival (OS). Performance of PBx was not associated with OS (HR 1.1, P = 0.070), and following propensity matching, 5-year OS did not differ between the two groups (56.5% PBx vs 58.4% no PBx, P = 0.247). A minority of patients with non-metastatic RPS undergo PBx. PBx does not negatively impact survival, but may indirectly improve outcomes in select patients by virtue of receipt of neoadjuvant therapy and attainment of complete tumor resection.

One hundred and eleven youth with mental ill-health underwent systematic clinical, laboratory and actigraphy monitoring to report associations between 24-h sleep–wake patterns and cardiometabolic risk factors. Multiple linear regression analyses, controlling for medication usage and class, age and sex, found significant associations between: later sleep onset and BMI; standard variation (SV) in the sleep offset with both insulin values and the updated homeostatic model assessment of insulin resistance (HOMA2-IR) values; and the SV of the sleep midpoint with both poorer fasting insulin, and HOMA2-IR values. Further longitudinal research is required to determine the causative relationships between 24-h sleep–wake cycle patterns, and cardiometabolic outcomes.

We aimed to investigate the association between neutrophil counts and first stroke and examine possible effect modifiers among treated hypertensive adults. This is a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). A total of 11,878 hypertensive adults with data on neutrophil counts at baseline were included in the current study. The primary outcome was first stroke. During a median follow-up of 4.5 years, 414 (3.5%) participants experienced a first stroke, including 358 with ischemic stroke, 55 with hemorrhagic stroke and one with uncertain type of stroke. Compared with participants in quartile 1 (

Background Although tumor size and mitotic rate are established prognostic factors for worse survival in patients undergoing surgical resection for gastric gastrointestinal stromal tumors, the impact of microscopic margins, or R1 resection, is not completely established. Methods Patients who received no neoadjuvant therapy and underwent surgical resection for stage I to III gastric gastrointestinal stromal tumors were identified from the 2010 to 2013 National Cancer Database and divided into 2 cohorts, R0 and R1 resections. Cox proportional hazards ratio and Kaplan Meier survival estimates were utilized to analyze 5-y overall survival. Results Of 2,084 patients, those with R1 resection (57, 2.7%) were more likely to have tumors >10 cm (28.1% vs 11.9%, odds ratio 3.51, P = .017) and stage III disease (26.3% vs 11.2%, odds ratio 2.26, P = .047). Although margin status was associated with higher risk tumors, it was not associated with receipt of adjuvant therapy. After multivariate Cox regression, R1 and R0 patients did not have a difference in 5-y overall survival (82.5% vs 88.6%, hazards ratio 1.26, P = .49). When stratified by stage of disease, there remained no difference in survival across all stages when comparing R1 and R0 patients. Conclusion Positive microscopic margins are uncommon but do not appear to impact survival outcomes in patients with resected localized gastric gastrointestinal stromal tumors.

Background The COVID-19 pandemic has resulted in large-scale healthcare restrictions to control viral spread, reducing operating room censuses to include only medically necessary surgeries. The impact of restrictions on which patients undergo surgical procedures and their perioperative outcomes is less understood. Methods Adult patients who underwent medically necessary surgical procedures at our institution during a restricted operative period due to the COVID-19 pandemic (March 23-April 24, 2020) were compared to patients undergoing procedures during a similar time period in the pre-COVID-19 era (March 25-April 26, 2019). Cardinal matching and differences in means were utilized to analyze perioperative outcomes. Results 857 patients had surgery in 2019 (pre-COVID-19) and 212 patients had surgery in 2020 (COVID-19). The COVID-19 era cohort had a higher proportion of patients who were male (61.3% vs. 44.5%, P

Summary Background We aimed to evaluate the relationship of body mass index (BMI) and waist circumference (WC) with the risk of new-onset hyperuricemia, and examine possible effect modifies in general hypertensive patients. Methods A total of 10 611 hypertensive patients with normal uric acid (UA) concentrations ( Results During a median follow-up duration of 4.4 years, 1663 (15.7%) participants developed new-onset hyperuricemia. When analyzed separately, increased BMI (≥25 kg/m2, quartile 3–4; OR, 1.46; 95% CI: 1.29–1.65), or increased WC (≥85 cm for females, quartile 3–4; OR, 1.24; 95% CI: 1.08–1.42; and ≥84 cm for males, quartile 3–4; OR, 1.30; 95% CI: 1.01–1.67) were each significantly associated with higher risk of new-onset hyperuricemia. When WC was forced into the model with BMI simultaneously, its significant association with new-onset hyperuricemia disappeared in females ( Conclusions Higher BMI, but not WC, is significantly and independently associated with an increased risk of new-onset hyperuricemia among hypertensive patients.

Background/Objective Recent prospective studies have shown poorer oncologic outcomes following minimally invasive surgery, which has led many surgeons to deeply inspect their practices. We reviewed our experience and evaluated the results of radical hysterectomy in patients with early stage cervical cancer. Methods This retrospective study included patients with early stage cervical cancer (Ia1 - IIa1) who were treated with radical hysterectomy from May 2006 to Dec 2016. Patients were divided into three groups according to the surgical approach: radical abdominal hysterectomy (RAH), laparoscopic radical hysterectomy (LRH), and robot-assisted radical hysterectomy (RRH). Results Learning curves of each type of surgery were obtained using the cumulative sum method. Survival rates were compared using Kaplan–Meier curves. To analyze the learning curve of a single surgeon, 89 patients were selected from the whole population. Learning curves of each group showed two distinct phases. The minimum number of cases required to achieve surgical improvement were 16 in RAH, 13 in LRH, and 21 in RRH. Progression-free survival (PFS) and overall survival did not vary between RAH and minimally invasive surgery (MIS) (p = .828 and p = .757, respectively). However, when stratified by the phases of the learning curves, patients included in the early phase of MIS showed a poorer PFS (p = .014). Conclusions Surgical proficiency could significantly affect the oncologic outcome in MIS. A prospective study regarding sufficient surgical competence is necessary for elaborate analysis of the feasibility of minimally invasive radical hysterectomy.

Multiauthority ciphertext-policy attribute-based encryption (MA-CP-ABE) is a promising technique for secure data sharing in cloud storage. As multiple users with same attributes have same decryption privilege in MA-CP-ABE, the identity of the decryption key owner cannot be accurately traced by the exposed decryption key. This will lead to the key abuse problem, for example, the malicious users may sell their decryption keys to others. In this paper, we first present a traceable MA-CP-ABE scheme supporting fast access and malicious users’ accountability. Then, we prove that the proposed scheme is adaptively secure under the symmetric external Diffie–Hellman assumption and fully traceable under the q -Strong Diffie–Hellman assumption. Finally, we design a traceable and revocable MA-CP-ABE system for secure and efficient cloud storage from the proposed scheme. When a malicious user leaks his decryption key, our proposed system can not only confirm his identity but also revoke his decryption privilege. Extensive efficiency analysis results indicate that our system requires only constant number of pairing operations for ciphertext data access.

Background and aims Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. Methods Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. Results There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: β = − 0.50, P β = − 0.14, P = 0.087; CT: β = − 0.20, P = 0.011; TT: β = − 1.19, P P for difference P for difference P for difference = 0.757). Conclusions Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer., Chinese breast cancer patients have not been well represented in clinical sequencing studies. Here the authors analyse the mutational landscape of 1,134 Chinese breast cancer patients, finding actionable targets and a higher prevalence of p53 and Hippo pathway mutations compared to Western cohorts.

Introduction The worldwide prevalence of diabetes has been increasing for decades; diabetes can lead to serious health problems and even death, but the effects of maintaining low fasting blood glucose (FBG) remain controversial. The purpose of this study was to investigate the relationship between FBG levels and all-cause mortality in a long-term follow-up cohort and to find a relatively safe range of FBG levels. Methods This study included 17,902 adults from a community-based cohort study in rural China who were prospectively followed from 2003 to 2018. Generalized estimating equations were used to evaluate the association between FBG and all-cause mortality, adjusting for pertinent covariates and auto-correlations among siblings. Results A total of 1053 (5.9%) deaths occurred during 15 years of follow-up. There was a significant U-shaped association between all-cause mortality and FBG. Compared with the reference group (FBG of 5.6 –

Background Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. As the clinical course can be variable, prognostic markers are needed to better stratify patients. Prior literature, composed of small series with limited sample size, has demonstrated that tumor-infiltrating lymphocytes (TILs) are an important prognostic marker in MCC. To validate these findings on a population level, we sought to analyze and report the prognostic value of TILs in a large national data set. Materials and Methods A retrospective observational cohort study was conducted of patients with nonmetastatic MCC from 2010 to 2015 using the National Cancer Database. Individual variables trending toward significance using a univariable analysis were included in a multivariable Cox proportional hazards model to assess their independent effect on overall survival (OS). TILs were subclassified into none, nonbrisk, and brisk and the survival analysis was performed. Propensity score–weighted multivariable analysis (PS MVA) was performed to adjust for additional confounding. Results A total of 2,182 patients met inclusion criteria: 611 (28.0%) were identified as having TILs present, and 1,571 (72.0%) had TILs absent in the tumor. On MVA, subdivision of TIL status into nonbrisk (hazard ratio [HR], 0.750; 95% confidence interval [CI], 0.602–0.933) and brisk (HR, 0.499; 95% CI, 0.338–0.735) was associated with incrementally improved OS compared with no TILs. The association of nonbrisk and brisk TILs with improved OS was retained on PS MVA (Nonbrisk: HR, 0.720; 95% CI, 0.550–0.944; Brisk: HR, 0.483; 95% CI, 0.286–0.814). Conclusion The presence of nonbrisk and brisk TILs is associated with incrementally improved OS in patients with nonmetastatic MCC in a large national data set. This pathologic feature can aid with risk stratification, estimation of prognosis, and, importantly, decision-making with respect to treatment intensification in high-risk patients. Implications for Practice Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous malignancy with variable clinical course. Prognostic markers are needed to better risk stratify patients. We present the largest retrospective observational cohort study of patients with nonmetastatic MCC using the National Cancer Database. Our analysis demonstrates an association between increasing degrees of tumor-infiltrating lymphocytes and incrementally improved survival. These conclusions improve pathologic risk stratification, and decision-making with respect to treatment intensification. Intensification may include adjuvant radiation therapy to the primary site after wide excision despite small tumor size, to the nodal basin in sentinel lymph node-negative patients, or offering closer follow-up.

Purpose Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. Materials and methods Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. Results The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. Conclusions Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

Body mass index (BMI) and waist-to-hip ratio (WHR) have been reported to be causally associated with cardiometabolic diseases in adults in European populations. However, this causality was less explored in East Asian populations and in children. Our study aimed to explore and compare the causal associations of general obesity (measured by BMI) and central obesity (measured by WHR) with cardiometabolic traits.We performed a Mendelian randomization (MR) analysis in 2030 unrelated children from two independent case-control studies in Beijing, China. BMI-associated single nucleotide polymorphisms (SNPs) and WHR-SNPs identified by previous genome-wide association studies were used as genetic instruments to examine the casual associations of BMI and WHR with cardiometabolic traits, including glycemic traits, blood lipids, and blood pressure. Each 1-SD increase in BMI and WHR were significantly associated with 0.111 mmol/L and 0.110 mmol/L increase in log-transformed fasting insulin (FINS), 0.049 and 0.060 increase in log-transformed HOMA-β, 0.112 and 0.108 increase in log-transformed HOMA-IR, 0.009 mmol/L and 0.015 mmol/L increase in log-transformed triglyceride, and 15.527 mmHg and 7.277 mmHg increase in systolic blood pressure, respectively (all P 0.05). The receiver operating characteristic curves showed that WHR had a stronger effect on FINS, HOMA-β, HOMA-IR, and triglyceride than BMI (all P 0.05).Using the MR method, we found that the genetic predisposition to higher BMI or WHR was associated with altered cardiometabolic traits in Chinese children. When compared with general obesity, central obesity might have stronger effects on glycemic traits and blood lipids among children.

The association between sleep conditions and arterial stiffness remains inconclusive. We aimed to investigate the relationship of sleep duration and quality with brachial-ankle pulse-wave velocity (baPWV) in hypertensive patients. A total of 14,485 hypertensive adults were included in this cross-sectional analysis. Information about sleep duration and quality was obtained via questionnaire. A baPWV level ≥1800 cm/s was defined as indicative of arterial stiffness. Compared with participants with a sleep duration β = 13.7 cm/s; 95% CI: 3.9, 23.5) and a nonsignificantly higher prevalence of arterial stiffness (39.7% vs. 33.0%; OR, 1.08; 95% CI: 0.99–1.19). Similarly, compared with participants with good or medium sleep quality, participants with poor sleep quality had a significantly higher baPWV level (β = 16.3 cm/s; 95% CI: 0.1, 32.6) and a nonsignificantly greater prevalence of arterial stiffness (36.6% vs. 35.3%; OR, 1.13; 95% CI: 0.97–1.32). When sleep duration and quality were examined jointly, participants with a sleep duration ≥8 h and/or poor sleep quality had a significantly higher baPWV level (β = 14.4 cm/s; 95% CI: 5.3, 23.4) and a greater prevalence of arterial stiffness (38.8% vs. 32.7%; OR, 1.10; 95% CI: 1.01–1.20) than those with a sleep duration

Transfusion guidelines have been established for severe anemia, but limited data is available regarding the utility of preoperative transfusion. This study evaluates the predictive factors and relative value of preoperative transfusion in oncologic patients with moderate anemia undergoing abdominal surgery. Using the American College of Surgeons National Surgical Quality Improvement Program database, adult patients with moderate anemia (hematocrit 21–27%) who underwent non-emergent abdominal oncologic resection from 2005 to 2017 were identified. Preoperative transfusion and non-transfused patients were propensity score matched based on baseline covariates. Outcomes were compared using univariate and Poisson regression analysis. Of 6222 patients, preoperative transfused (N = 1000, 16.1%) patients were more likely to have bleeding disorders (12.1% vs 6.7%, p

AIMS To investigate the association of baseline serum uric acid (UA) with new-onset diabetes, and to explore the possible effect modifiers in Chinese adults with hypertension. MATERIALS AND METHODS A total of 14 943 hypertensive patients with available UA measurements and without diabetes at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). Participants were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0 mmol/L at the exit visit. RESULTS Over a median follow-up of 4.5 years, 1623 participants (10.9%) developed diabetes. Overall, there was a positive association between baseline UA and new-onset diabetes in women (per SD increment; adjusted odds ratio [OR] 1.14, 95% confidence interval [CI] 1.07, 1.23), but not in men (adjusted OR 1.01, 95% CI 0.92, 1.10). Moreover, a stronger positive association between baseline UA and new-onset diabetes was found among women with lower time-averaged on-treatment systolic blood pressure during the treatment period (

Background Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. Methods Patients with American Joint Committee on Cancer (8th edition) stage I–IV MCC treated at our institution were identified (1/1/2008–2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. Results Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20–66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). Conclusions Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.

Jiuzhaigou, located in the transitional area between the Qinghai–Tibet Plateau and the Sichuan Basin, is highly prone to geological hazards (e.g., rock fall, landslide, and debris flow). High-performance-based hazard prediction models, therefore, are urgently required to prevent related hazards and manage potential emergencies. Current researches mainly focus on susceptibility of single hazard but ignore that different types of geological hazards might occur simultaneously under a complex environment. Here, we firstly built a multi-geohazard inventory from 2000 to 2015 based on a geographical information system and used satellite data in Google earth and then chose twelve conditioning factors and three machine learning methods—random forest, support vector machine, and extreme gradient boosting (XGBoost)—to generate rock fall, landslide, and debris flow susceptibility maps. The results show that debris flow models presented the best prediction capabilities [area under the receiver operating characteristic curve (AUC 0.95)], followed by rock fall (AUC 0.94) and landslide (AUC 0.85). Additionally, XGBoost outperformed the other two methods with the highest AUC of 0.93. All three methods with AUC values larger than 0.84 suggest that these models have fairly good performance to assess geological hazards susceptibility. Finally, evolution index was constructed based on a joint probability of these three hazard models to predict the evolution tendency of 35 unstable slopes in Jiuzhaigou. The results show that these unstable slopes are likely to evolve into debris flows with a probability of 46%, followed by landslides (43%) and rock falls (29%). Higher susceptibility areas for geohazards were mainly located in the southeast and middle of Jiuzhaigou, implying geohazards prevention and mitigation measures should be taken there in near future.

To evaluate the association between plasma retinol levels with all‐cause mortality and investigate the possible effect modifiers in general hypertensive patients with no previous cardiovascular disease (CVD). This case‐control study was nested in the China Stroke Primary Prevention Trial (CSPPT), a randomized, double‐blind, controlled trial conducted in 32 communities in Anhui and Jiangsu provinces in China. The current study included 617 cases of all‐cause mortality and 617 controls matched on age (≤1 year), sex, treatment group, and study site. All‐cause mortality was the main outcome in this analysis, which included death due to any reason. The median follow‐up duration was 4.5 years. Overall, there was a U‐shaped relation of plasma retinol with all‐cause mortality. In the threshold effect analysis, the risk of all‐cause mortality significantly decreased with the increase in plasma retinol (per 10 μg/dL increments: OR, 0.73; 95% CI: 0.61‐0.87) in participants with plasma retinol

We aimed to investigate the association of brachial–ankle pulse wave velocity (baPWV) with carotid plaque presence and carotid plaque number in a Chinese hypertensive population. A total of 13,554 hypertensive subjects from the China Stroke Primary Prevention Trial (CSPPT) were recruited. Arterial stiffness and carotid plaque were evaluated by baPWV and B-mode ultrasonography, respectively. Multivariate logistic regression analysis was used to determine the correlation of baPWV and carotid plaque presence. Multinomial logistic regression analysis was used to determine the correlation of baPWV and carotid plaque number. Further interactions between baPWV and carotid plaque presence were examined using subgroup analysis. Continuous baPWV was positively correlated with carotid plaque presence (OR = 1.05, 95% CI: 1.04–1.07) and carotid plaque number (one- to two-plaque group: OR = 1.04, 95% CI: 1.02–1.06; three-or-more-plaque group: OR = 1.09, 95% CI: 1.07–1.12). When baPWV was classified into quartiles, with the lowest quartile as reference, the ORs for having one, two, or three or more plaques increased in parallel with the quartiles of baPWV, indicating a dose-dependent effect. In a subgroup analysis, the association of baPWV and carotid plaque presence was more pronounced among younger participants (OR: 1.14 vs. 1.06 and 1.03 for the age groups P for interaction

Objective Data on the association between visit-to-visit variability (VVV) in blood pressure (BP) and the risk of stroke among hypertensive patients with chronic kidney disease (CKD) is limited. We aimed to evaluate the relation of VVV in BP with the risk of stroke, and examine any possible effect modifiers in hypertensive patients with mild-to-moderate CKD. Methods This is a post-hoc analysis of the China Stroke Primary Prevention Trial. A total of 3091 patients with estimated glomerular filtration rate 30-60 ml/min per 1.73 m and/or proteinuria at baseline, without occurring stroke and with BP measurements of at least two visits from randomization to the 12-month visit were included. The main VVV in BP was expressed as SD. The primary outcome was first stroke. Results The median subsequent treatment duration was 3.7 years. After multivariable adjustment, including baseline SBP and mean SBP during the first 12-month follow-up, there was a significantly positive relationship of SD SBP with the risk of subsequent first stroke (per SD increment; odds ratio, 1.41; 95% confidence interval: 1.17-1.69) and first ischemic stroke (odds ratio, 1.55; 95% confidence interval: 1.26-1.90). Results were consistent across various subgroups, including age, sex, baseline SBP, treatment compliance, and mean SBP, concomitant usage of calcium channel blocker during the first 12-month follow-up period. Similar trends were also found for coefficient of variation SBP, and SD or coefficient of variation DBP. However, there was no significant association between BP variability and first hemorrhagic stroke. Conclusion In hypertensive adults with mild-to-moderate CKD, visit-to-visit variability in BP was significantly associated with the risk of subsequent first stroke.

We aimed to evaluate the relationship of plasma Mg with the risk of new-onset hyperuricaemia and examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric acid (UA) Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 1685 participants were included in the present study. The main outcome was new-onset hyperuricaemia defined as a UA concentration ≥417 μmol/l in men or ≥357 μmol/l in women. The secondary outcome was a change in UA concentration defined as UA at the exit visit minus that at baseline. During a median follow-up duration of 4·3 years, new-onset hyperuricaemia occurred in 290 (17·2 %) participants. There was a significantly inverse relation of plasma Mg with the risk of new-onset hyperuricaemia (per sd increment; OR 0·85; 95 % CI 0·74, 0·99) and change in UA levels (per sd increment; β −3·96 μmol/l; 95 % CI −7·14, −0·79). Consistently, when plasma Mg was analysed as tertiles, a significantly lower risk of new-onset hyperuricaemia (OR 0·67; 95 % CI 0·48, 0·95) and less increase in UA levels (β −8·35 μmol/l; 95 % CI −16·12, −0·58) were found among participants in tertile 3 (≥885·5 μmol/l) compared with those in tertile 1 (

OBJECTIVE The study objectives were to characterize surgical outcomes for malignant small bowel obstruction (MaSBO) as compared to other small bowel obstructions (SBO) and to develop a prediction model for postoperative mortality for MaSBO. SUMMARY BACKGROUND DATA MaSBO is a morbid complication of advanced cancers for which the optimal management remains undefined. METHODS Patients who underwent surgery for MaSBO or SBO were identified from the National Surgical Quality Improvement Program (2005-2017). Outcomes [30-day morbidity, unplanned readmissions, mortality, postoperative length of stay (LOS)] were compared between propensity score-matched MaSBO and SBO patients. An internally validated prediction model for mortality in MaSBO patients was developed. RESULTS Of 46,706 patients, 1612 (3.5%) had MaSBO. Although MaSBO patients were younger than those with SBO (median 63 vs 65 years, P < 0.001), they were otherwise more clinically complex, including a higher proportion with recent weight loss (22.0% vs 4.0%, P < 0.001), severe hypoalbuminemia (18.6% vs 5.2%, P < 0.001), and cytopenias. After matching (N = 1609/group), MaSBO was associated with increased morbidity [odds ratio (OR) 1.2, P = 0.004], but not readmission (OR 1.1, P = 0.48) or LOS (incidence rate ratio 1.0, P = 0.14). The odds of mortality were significantly higher for MaSBO than SBO (OR 3.3, P < 0.001). A risk-score model predicted postoperative mortality for MaSBO with an optimism-adjusted Brier score of 0.114 and area under the curve of 0.735. Patients in the highest-risk category (11.5% of MaSBO population) had a predicted mortality rate of 39.4%. CONCLUSION Surgery for MaSBO is associated with substantial morbidity and mortality, necessitating careful patient evaluation before operative intervention.

Increased meningitis caused by extensively drug-resistant bacillary presents a significant challenge in antibiotic selection. The aim of our study was to evaluate the efficacy and safety of polymyxin in the treatment of post-neurosurgical meningitis due to the extensively drug-resistant bacillary in children. We performed a retrospective study on post-neurosurgical meningitis caused by the extensively drug-resistant bacillary in children, who were treated with polymyxin for ≥ 3 days. Among five post-neurosurgical meningitis cases that were included, the children were infected by Acinetobacter baumannii (n = 3), Klebsiella pneumonia (n = 1), and Pseudomonas aeruginosa (n = 1). The drug susceptibility test showed that they were extensively drug-resistant bacillary. Two patients received intravenous polymyxin E. Three children received intravenous combined with intraventricular injection of polymyxin B. One patient infected by Klebsiella pneumonia eventually died of septic shock. No serious adverse effects of polymyxin were observed. Polymyxin is a safe and effective therapy for post-neurosurgical, multidrug-resistant bacillary meningitis in children.

Background Intronic pentanucleotide insertion in the sterile alpha motif domain-containing 12 gene was recently identified as the genetic cause of familial cortical myoclonic tremor with epilepsy type 1. Objectives We thereafter conducted a multimodal MRI research to further understand familial cortical myoclonic tremor with epilepsy type 1. Methods We enrolled 31 patients carrying heterozygous pathogenic intronic pentanucleotide insertion in the sterile alpha motif domain-containing 12 gene and 31 age- and sex-matched healthy controls. We compared multimodal MRI metrics, including voxel-based morphometry, fractional anisotropy of diffuse tensor imaging, frequency-dependent percent amplitude fluctuation, and seed-based functional connectivity of resting-state functional MRI. Results Significant decreased gray matter volume was found in the cerebellum. Percent amplitude fluctuation analysis showed significant interaction effect of "Frequency by Group" in three regions, including the vermis VIII, left cerebellar lobule VIII, and left precentral gyrus. Specifically, the lowest-frequency band exhibited significant increased percent amplitude fluctuation in patients in the two cerebellar subregions, whereas the highest-frequency band exhibited decreased percent amplitude fluctuation in the precentral gyrus in patients. Discriminative analysis by support vector machine showed a mean accuracy of 82% (P = 1.0-5 ). An increased functional connectivity between vermis VIII and the left precentral gyrus was found in patients with familial cortical myoclonic tremor with epilepsy type 1. A positive correlation between the percent amplitude fluctuation in the left cerebellar lobule VIII and duration of cortical tremor was also found. Conclusion The cerebellum showed both structural and functional damages. The distinct change of spontaneous brain activity, that is, increased ultra-low-frequency amplitude in the cerebellum and the decreased higher-frequency amplitude in the motor cortex, might be a pathophysiological feature of familial cortical myoclonic tremor with epilepsy type 1. © 2020 International Parkinson and Movement Disorder Society.

To investigate the relationship between previous cesarean section (C/S) and risk for post-molar gestational trophoblastic neoplasia (GTN).Data from patients who were treated for hydatidiform moles between 1995 and 2016 were retrospectively reviewed. Patient age, gravidity, parity, abortion history, gestational age, pretreatment beta-human chorionic gonadotropin (HCG), previous molar pregnancy, clinical symptoms, enlarged uterus, theca lutein cyst, type of GTN, World Health Organization risk score, chemotherapy, and mode of delivery were recorded. Hazard ratios (HR) and 95% confidence intervals (CI) for variables associated with the occurrence of post-molar GTN and invasive mole were estimated by univariate and multivariate Cox proportional hazards models.From 1995 to 2016, 182 patients were diagnosed with molar pregnancy and underwent treatment. Patients with previous C/S (C/S group) had higher age (37.0 vs 32.8. p = 0.004), gravidity (3.1 vs 2.0, p 0.001), and parity (1.6 vs 0.9, p 0.001) than patients without previous C/S (non-C/S group). Post-molar GTN (43.5 vs 26.5%, p 0.001), invasive mole (21.7 vs 3.7%, p 0.001), hysterectomy (28.3 vs 6.6%, p 0.001), and chemotherapy (45.7 vs 28.7%, p = 0.03) were more frequent in the C/S group. In multivariate analysis, independent risk factors for post-molar GTN were previous C/S (HR 5.1, 95% CI 2.1-12.7), abortion history (HR 6.3, 95% CI 2.5-15.6), and pretreatment β-hCG (HR 1.3, 95% CI 1.1-1.6).In this study, C/S was a strong risk factor for occurrence of post-molar GTN and invasive mole. Aggressive treatment, such as multi-agent chemotherapy or hysterectomy, can be considered for hydatidiform moles in patients with a C/S history.