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The male abnormal gene family 21 (imab21/i), was initially identified iniC. elegans/i. Since its identification, studies from different groups have shown that it regulates development of ocular tissues, brain, heart and liver. However, its functional mechanism remains largely unknown. Here, we demonstrate that Mab21L1 promotes survival of lens epithelial cells. Mechanistically, Mab21L1 upregulates expression of αB-crystallin. Moreover, our results show that αB-crystallin prevents stress-induced phosphorylation of p53 at S-20 and S-37 through abrogating the activation of the upstream kinases, ATR and CHK1. As a result of suppressing p53 activity by αB-crystallin, Mab21L1 downregulates expression of Bak but upregulates Mcl-1 during stress insult. Taken together, our results demonstrate that Mab21L1 promotes survival of lens epithelial cells through upregulation of αB-crystallin to suppress ATR/CHK1/p53 pathway.

Summary Background The use of magnetically controlled capsules for gastroscopy is in the early stages of clinical adoption. We aimed to evaluate the safety and efficacy of a fully automated magnetically controlled capsule endoscopy (FAMCE) system in clinical practice for gastroscopy and small bowel examination. Methods We did a prospective, comparative study to evaluate the safety and efficacy of FAMCE. Patients from two hospitals in Chongqing, China were consecutively enrolled. Eligible participants were aged 18–80 years with suspected gastric pathology and no previous surgery. Participants underwent FAMCE for screening of gastric lesions, then conventional transoral gastroscopy 2 h later, and stomach examination results were compared. The primary outcome was the rate of complete detection of gastric anatomy landmarks (cardia, fundus, body, angulus, antrum, and pylorus) by FAMCE. Secondary outcomes were the time required for gastric completion by FAMCE, the rate of detection of gastric lesions by FAMCE compared with conventional transoral gastroscopy, and the rate of complete small bowel examination. Adverse events were also evaluated. The study was registered in the Chinese Clinical Trial Registry, ChiCTR2000040507. Findings Between May 12 and Aug 17, 2020, 114 patients (mean age 44·0 years [IQR 34·0–55·0]; 63 [55%] female) were enrolled. The rate of complete detection of gastric anatomical structures by FAMCE was 100% (95% CI 99·3–100·0). The concordance between FAMCE and conventional transoral gastroscopy was 99·61% (99·45–99·78). The mean completion time of a gastroscopy with FAMCE was 19·17 min (SD 1·43; median 19·00, IQR 19·00–20·00), compared with 5·21 min (2·00; 5·18, 3·68–6·45) for conventional transoral gastroscopy. In 114 enrolled patients, 214 lesions were detected by FAMCE and conventional transoral gastroscopy. Of those, 193 were detected by both modalities. FAMCE missed five pathologies (four cases of gastritis and one polyp), whereas conventional transoral gastroscopy missed 16 pathologies (12 cases of gastritis, one polyp, one fundal xanthoma, and two antral erosions). FAMCE was able to provide a complete small bowel examination for all 114 patients and detected intestinal lesions in 50 (44%) patients. During the study, two (2%) patients experienced adverse events. No serious adverse events were recorded, and there was no evidence of capsule retention. Interpretation The performance of FAMCE is similar to conventional transoral gastroscopy in completion of gastric examination and lesion detection. Furthermore, it can provide a complete small bowel examination. Therefore, FAMCE could be effective method for examination of the gastrointestinal tract. Funding Chinese National Key Research and Development Program.

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder with an autosomal recessive inherited pattern. It is mainly characterized by deficiencies in lysosome-related organelles, such as melanosomes and platelet-dense granules, and leads to albinism, visual impairment, nystagmus, and bleeding diathesis. A small number of patients will present with granulomatous colitis or fatal pulmonary fibrosis. At present, mutations in ten known genetic loci (HPS1–11) have been identified to be the genetic cause of HPS. In this study, we enrolled a consanguineous family who presented with typical HPS phenotypes, such as albinism, visual impairment, nystagmus, and bleeding diathesis. Whole-exome sequencing and Sanger sequencing were applied to explore the genetic lesions of the patient. A novel homozygous frameshift mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 was identified and cosegregated in the family members. Furthermore, real-time PCR confirmed that the mutation decreased the expression of HPS3, which has been identified as the disease-causing gene of HPS type 3. According to ACMG guidelines, the novel mutation, resulting in a premature stop codon at amino acid 442, is a pathogenic variant. In summary, we identified a novel mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 in a family with HPS. Our study expanded the variant spectrum of the HPS3 gene and contributed to genetic counseling and prenatal genetic diagnosis of the family.

To observe the effect of fire needling on psoriasis-like lesion and the signal transducer and activator of transcription 3 (STAT3) pathway in mice and compare the therapeutic effect between different interventions of fire needling therapy (surrounding technique of fire needling, fire needling at "Dazhui" [GV 14] and "Zusanli" [ST 36]).Thirty male BALB/c mice were randomized into a blank group, a model group, a dexamthasone group, a surrounding technique group and an acupoint group, 6 mice in each one. Except the blank group, the mice in the rest groups were established as psoriasis-like lesion model by topical application with imiquimod cream, once daily, consecutively for 8 days. From day 4 to day 8, in the dexamthasone group, gastric infusion with 0.2 mL dexamthasone was administered, once daily. On day 4, 6 and 8, in the surrounding technique group, fire needling was exerted around the skin lesion; and fire needling was applied to "Dazhui" (GV 14) and "Zusanli" (ST 36) in the acupoint group, once a day. The changes in skin lesion on the dorsal parts of mice were observed in each group to score the psoriasis area and severity index (PASI). Using HE staining, the dermal morphological changes and epidermal thickness were observed in the mice of each group. The positive expression of proliferating cell-associated antigen Ki-67 was determined by immunofluorescence. Immunohistochemistry method was used to determine the expressions of , and T cells of skin tissue in each group. Using real-time PCR, the expressions of interleukin (IL)-17, IL-22, tumor necrosis factor α(TNF-α) mRNA were determined. Western blot method was adopted to determine the protein expressions of STAT3 and p-STAT3 in skin tissue in each group.Compared with the blank group, the scores of each item and the total scores of PASI, as well as the epidermal thickness were all increased in the mice of the model group (Fire needling therapy improves skin lesion severity in imiquimod induced psoriasis-like lesion of the mice, which is probably related to the inhibition of STAT3 pathway activation and the decrease of Th17 inflammatory factors expression. The systemic regulation of fire needling at "Dazhui" (GV 14) and "Zusanli" (ST 36) is superior to the local treatment.

Background Unlike N-terminal pro-B-type natriuretic peptide (NT-proBNP), which have been extensively studied, little is known about the role of N-terminal pro-C-type natriuretic peptide (NT-proCNP) for predicting survival post transcatheter aortic valve replacement (TAVR). Methods A total of 309 patients were included in the analysis. Patients were grouped into quartiles (Q1–4) according to the baseline NT-proCNP value. Blood for NT-proCNP analysis was obtained prior to TAVR procedure. The primary endpoint was mortality after a median follow-up of 32 months. Multivariable Cox proportional hazards regression models analyzed prognostic factors. The predictive capability was compared between NT-proBNP and NT-proCNP using receiver operator curve (ROC) analysis. Results A total of 309 subjects with the mean age of 76.8 ± 6.3 years, among whom 58.6% were male, were included in the analysis. A total of 58 (18.8%) patients died during follow-up. Cox multivariable analyses indicated society of thoracic surgeons (STS)-score was a strong independent predictor for mortality (hazard ratio (HR) 1.08, 95% confidential interval (CI) 1.05–1.12, P P = 0.025) and All-cause mortality (HR 1.01, 95% CI 1.00–1.03, P = 0.027), whereas NT-proBNP showed a small effect size on mortality. ROC analysis indicated that NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with left ventricular ejection fraction (LVEF) P = 0.0453]. Conclusions NT-proCNP and STS-Score were the independent prognostic factors of mortality among TAVR patients. Furthermore, NT-proCNP was superior to NT-proBNP for TAVR risk evaluation in patients with LVEF Trial registration NCT02803294, 16/06/2016.

Context As a major active iridoid glycoside from Gardenia jasminoides J. Ellis (Rubiaceae), geniposide possesses various pharmacological activities, including anti-platelet aggregation and anti-inflammatory action. Objectives This study explores the effect of geniposide in diabetic wound model by anti-inflammatory action. Materials and methods Diabetic rodent model in Wistar rats was induced by streptozotocin combined with high-fat feed. The selected rats were divided into control group, the diabetic model group and geniposide subgroups (200, 400 and 500 mg/kg), and orally administrated once daily with saline or geniposide. Wound area and histochemical indicators were measured on day 7 after continuous administration, to assess lesion retraction, inflammatory cells and fibroblasts. Results Geniposide notably enhanced lesion retraction by 1.06–1.84 times on day 7 after surgical onset in diabetic rats (p

Diabetic neuropathic pain (DNP) is a troublesome diabetes complication all over the world. P2X3 receptor (P2X3R), a purinergic receptor from dorsal root ganglion (DRG), has important roles in neuropathic pain pathology and nociceptive sensations. Here, we investigated the involvement of DRG P2X3R and the effect of 2 Hz electroacupuncture (EA) on DNP. We monitored the rats’ body weight, fasting blood glucose level, paw withdrawal thresholds, and paw withdrawal latency, and evaluated P2X3R expression in DRG. We found that P2X3R expression is upregulated on DNP, while 2 Hz EA is analgesic against DNP and suppresses P2X3R expression in DRG. To evaluate P2X3R involvement in pain modulation, we then treated the animals with A317491, a P2X3R specific antagonist, or α β-me ATP, a P2X3R agonist. We found that A317491 alleviates hyperalgesia, while α β-me ATP blocks EA’s analgesic effects. Our findings indicated that 2 Hz EA alleviates DNP, possibly by suppressing P2X3R upregulation in DRG.

To evaluate the efficacy of trabeculo-canalectomy in treating glaucoma patients, a retrospective investigation of 53 glaucoma patients (53 eyes) who underwent trabeculo-canalectomy was conducted at the First Affiliated Hospital of Nanjing Medical University, China, from April 2017 to January 2019. Intraocular pressure (IOP), visual acuity, surgical success rates, medications, and complications were monitored at post-operative 1 day, 1 week, 1, 3, 6, 12 and 24 months. Surgical success criteria were defined as 6 mm Hg≤IOP≤21 mmHg with or without additional medications. Our results showed that average IOP was statistically significant between pre-operative visit and each follow-up visit (all P

Background Information on possible donor-derived transmission events in China is limited. We evaluated the impacts of liver transplantation from infected deceased-donors, analyzed possible donor-derived bacterial or fungal infection events in recipients, and evaluated the etiologic agents’ characteristics and cases outcomes. Methods A single-center observational study was performed from January 2015 to March 2017 to retrospectively collect data from deceased-donors diagnosed with infection. Clinical data were recorded for each culture-positive donor and the matched liver recipient. The microorganisms were isolated and identified, and antibiotic sensitivity testing was performed. The pathogens distribution and incidence of possible donor-derived infection (P-DDI) events were analyzed and evaluated. Results Information from 211 donors was collected. Of these, 82 donors were infected and classified as the donation after brain death category. Overall, 149 and 138 pathogens were isolated from 82 infected donors and 82 matched liver recipients, respectively. Gram-positive bacteria, Gram-negative bacteria, and fungi accounted for 42.3% (63 of 149), 46.3% (69 of 149), and 11.4% (17 of 149) of pathogens in infected donors. The incidence of multidrug-resistant bacteria was high and Acinetobacter baumannii was the most concerning species. Infections occurred within the first 2 weeks after liver transplantation with an organ from an infected donor. Compared with the noninfection recipient group, the infection recipient group experienced a longer mechanical ventilation time (P = .004) and intensive care unit stay (P = .003), a higher incidence of renal dysfunction (P = .026) and renal replacement therapy (P = .001), and higher hospital mortality (P = .015). Possible donor-derived infection was observed in 14.6% of cases. Recipients with acute-on-chronic liver failure were more prone to have P-DDI than recipients with other diseases (P = .007; odds ratio = 0.114; 95% confidence interval, .025–.529). Conclusions When a liver recipient receives a graft from an infected deceased-donor, the postoperative incidence of infection is high and the infection interval is short. In addition, when a possible donor-derived, drug-resistant bacterial infection occurs, recipients may have serious complications and poor outcomes.

To observe the effect of moxibustion on skin lesions and immune inflammatory response in psoriasis mice, and to explore the possible mechanism of moxibustion for psoriasis.A total of 32 male BALB/c mice were randomly divided into a normal group, a model group, a moxibustion group and a medication group, 8 mice in each group. Psoriasis model was induced by applying 5% imiquimod cream on the back for 7 days in the model group, the moxibustion group and the medication group. At the same time of model establishment, the moxibustion group was treated with suspension moxibustion on skin lesions on the back, 20 min each time, once a day; the medication group was treated with 1 mg/kg methotrexate tablet solution by gavage, once a day. Both groups were intervened for 7 days. The daily changes of skin lesions were observed, and the psoriasis area and severity index (PASI) score was evaluated; the histopathological changes of skin lesions were observed by HE staining; the positive expression of proliferating cell nuclear antigen (PCNA) and T lymphocyte surface marker CDThe increased and hypertrophy scale, dry skin, red and swollen epidermis and obvious infiltration were observed in the model group, and each score and total score of PASI were higher than those in the normal group (Moxibustion could effectively improve the scale and infiltration of skin lesions in psoriasis mice. Its mechanism may be related to inhibiting inflammatory response and regulating immunity.

To establish an animal model of reflux renal damage through bladder outlet obstruction.Sixty male C57BL/6 mice aged 6-8 weeks were randomly assigned to a control group, a sham operation group, and a partial bladder outlet obstruction (PBOO) group, with 20 mice in each group. Laparotomy were performed on the PBOO mice under anesthesia in order to separate the bladder necks and to perform guided partial ligation of the bladder neck with a metal rod of 0.3 mm diameter. Mice in the sham operation group had laparotomy and had their bladder necks separated without ligation. The control group did not receive any treatment. 7 days after the surgery, 12 surviving mice were randomly selected from each group to observe the general changes of the bladder, ureter, renal pelvis and kidney. Retrograde urography was performed through the bladder. Kidney tissues were extracted for histopathological analysis. The expression levels of Vimentin, proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were examined with Western blot, immunohistochemistry and immunofluorescence staining tests, respectively.Compared with the control and sham operation group, the bladder, ureter, and renal pelvis of the mice in the PBOO group were significantly enlarged, vesicoureteral reflux was more obvious, the kidney volume and mass increased (After PBOO, the bladder, ureter, and kidney of the mice showed obvious morphological alteration and presented reflux renal fibrosis-like damage. This can be used as an animal model to study the pathological alteration mechanism and therapeutic measures of renal fibrosis caused by bladder outlet obstruction.

West Nile virus (WNV) was first isolated in mainland China from mosquitoes in Jiashi County, Kashgar Region, Xinjiang in 2011, following local outbreaks of viral meningitis and encephalitis caused by WNV. To elaborate the epidemiological characteristics of the WNV, surveillance of WNV infection in Kashgar Region, Xinjiang from 2013 to 2016 were carried out. Blood and CSF samples from surveillance human cases, blood of domestic chicken, cattle, sheep and mosquitoes in Kashgar Region were collected and detected. There were human 65 WNV Immunoglobulin M (IgM) antibody positive cases by ELISA screening, 6 confirmed WNV cases by the plaque reduction neutralization test (PRNT) screening. These cases occurred mainly concentrated in August to September of each year, and most of them were males. WNV-neutralizing antibodies were detected in both chickens and sheep, and the positive rates of neutralizing antibodies were 15.5% and 1.78%, respectively. A total of 15,637 mosquitoes were collected in 2013–2016, with Culex pipiens as the dominant mosquito species. Four and 1 WNV-positive mosquito pools were detected by RT-qPCR in 2013 and 2016 respectively. From these data, we can confirm that Jiashi County may be a natural epidemic foci of WNV disease, the trend highlights the routine virology surveillance in WNV surveillance cases, mosquitoes and avian should be maintained and enhanced to provide to prediction and early warning of outbreak an epidemic of WNV in China.

The Schistosoma japonicum fatty acid-binding protein (FABP) is used in the cell membrane to absorb and transport fatty acids, which cannot be resynthesized by the organism and combined with hydrophobic ligands. Among the 5 stages of the worm life cycle examined, FABP messenger ribonucleic acid (mRNA) expression was highest in male adult worms, followed by the liver-stage schistosome, and was the lowest in the lung-stage schistosome. The fabp gene-coding region was cloned and expressed to obtain recombinant S. japonicum FABP (rSjFABP) with a molecular weight of approximately 18 kDa. Mice were then immunized against rSjFABP to prepare anti-FABP serum. Using immunohistochemical techniques, FABP protein was found to localize to the eggshell, parenchyma, and digestive tract. Double-stranded RNA-mediated knockdown of FABP mRNA by RNA interference decreased the number of transcripts by >70%. Moreover, the egg production rate decreased, whereas the abnormal egg ratio was significantly increased in the FABP-silenced group compared with the negative control group (P < 0.05). These results demonstrate that FABP localizes in adults and in various stages. FABP contributes to the egg-laying capacity of adults, which may be related to the reproductive function of S. japonicum.

Atherosclerosis, the major risk of cardiovascular events, is a chronic vascular inflammatory disease. Pterostilbene is a naturally occurring dimethylated analogue of resveratrol and has recently been demonstrated to be beneficial against cardiovascular diseases. However, the underlying mechanisms of pterostilbene on atherosclerosis remain elusive. Experimental atherosclerosis was induced by a high-fat diet (HFD) in apolipoprotein E knockout (ApoE-/-) mice. Pterostilbene was administered intragastrically for 16 weeks. We found that pterostilbene significantly attenuated thoracic and abdominal atherosclerotic plaque formation in HFD-fed ApoE-/-mice, accompanied by modulated lipid profiles and reduced production of proinflammatory cytokines (including IL-6, IFN-γ, and TNF-α). In addition, pterostilbene restored vascular redox balance in thoracic and abdominal aorta, evidenced by enhanced catalase (CAT) expression and activities, and decreased malondialdehyde and H2O2 production. Notably, pterostilbene specifically induced CAT expression and activities in the vascular smooth muscle cells (VSMCs) of thoracic and abdominal aorta. In vitro, pterostilbene markedly promoted the expression and activity of CAT and decreased ox-low-density lipoprotein (LDL)-mediated VSMC proliferation and intracellular H2O2 production, which was abolished by CAT siRNA knockdown or inhibition. Pterostilbene-induced CAT expression was associated with inhibition of Akt, PRAS40, and GSK-3β signaling activation and upregulation of PTEN. Our data clearly demonstrated that pterostilbene exerted an antiatherosclerotic effect by inducing CAT and modulating the VSMC function.

Background: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial encephalomyopathy caused by multiple mtDNA abnormalities. There is little information about the changes of ocular fundus with CPEO. The aim of this work was to measure and evaluate changes in the macular retinal thickness and optic nerve head in patients with CPEO using spectral-domain optical coherence tomography and to compare the findings with those of healthy individuals. Methods: Totally, 18 CPEO patients were enrolled in this study. Healthy volunteers matched for gender, age, and diopter settings were included as a control group. The retinal thickness of macular central fovea, inner and outer retinal layer thickness of perifoveal macular, optic nerve head parameters, and peripapillay retinal nerve fiber layer thickness (pRNFLT) for all included cases were measured using spectral-domain optical coherence tomography. A paired t test was used to compare the differences in the studied parameters between the two groups. The correlations between macular retinal thickness, pRNFLT, disease duration, and age of onset were also analyzed. Results: Among the macular parameters, retinal thickness of macular central fovea (t = -2.135, P < 0.05) and outer retinal layer thickness (t = -1.994, P < 0.05) of patients in the CPEO group were statistically significant lower than those of patients in the normal control group. For the optic nerve head parameters, the patients in the CPEO group showed a larger rim volume (t = -2.499, P < 0.05) and nerve head volume (t = -2.103, P < 0.05). The overall pRNFLT of patients in the CPEO group was statistically significant lower than that of patients in the control group (t = -4.125, P < 0.05). The comparison of pRNFLT in eight sectors showed that the pRNFLT of patients in the CPEO group was statistically significant lower than that of the control group mainly in the inferior and temporal sectors. The degree of pRNFL defect negatively correlated with the disease duration (r = -0.583, P < 0.05). Conclusions: The retinal thickness of patients with CPEO was significantly thinner, which was mostly the outer retina. The patients’ optic discs had a low volume and the loss of the retinal nerve fiber layer was obvious. With the extension of the disease duration, the retinal nerve fiber layer defect was even more significant. Key words: Optical coherence tomography; Chronic progressive external ophthalmoplegia; Retina; Nerve fiber layer

BACKGROUND Cerebellar fastigial nucleus electrical stimulation (FNS) in rats has been shown to protect against brain ischemia/reperfusion (I/R) damage. Activation of telomerase has been reported to provide neuroprotection in animal models of stroke. OBJECTIVE The aim of this study was to explore whether precondition FNS increases the expression of telomerase reverse transcriptase (TERT) and telomerase activity in rats after cerebral I/R injury. METHODS One day after continuous stimulation of the fastigial cerebellar nucleus for 1 h, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h, 48 h and 72 h, while the I/R control groups received the same treatment without FNS. Ischemic lesion volumes were measured following TTC staining. The number of apoptotic cells was measured by using TUNEL assays. Subsequently, telomerase activity was examined by using TRAP-silver staining. Additionally, the expression level of TERT mRNA was assessed by using real-time fluorescence quantitative PCR. Finally, the expression of TERT protein was measured by using Western blotting. RESULTS The results of our study demonstrated that FNS significantly decreased infarct volumes and improved neurological deficits when compared with the I/R control group. The telomerase activity in the I/R + FNS group was significantly increased compared with that in the I/R control group, particularly in the 24 h reperfusion subgroup (P

To retrospectively evaluate the value of MR features based on Liver Imaging Reporting and Data System (LI-RADS ver.2017) for identifying the status of cytokeratin (CK) 19 expression of HCC before surgery.A total of 201 patients with 207 HCCs who underwent MR imaging were reviewed retrospectively. MR features based on LI-RADS ver.2017 as well as clinical data were compared between CK19-positive (n = 51) and CK19-negative (n = 156) HCCs groups. Potential predictive parameters were identified by univariate and multivariate logistic regression analysis and diagnostic odds ratios (ORs) were recorded.MR features including targetoid appearance (p = 0.001) was more frequently observed while non-peripheral "washout" (p 0.0001) and non-rim arterial phase hyper-enhancement (p 0.0001) were found less frequently in CK19-positive HCCs compared to CK19-negative HCCs. At multivariate analysis, serum alphafetoprotein (AFP)20 ng/ml (OR = 5.9) and targetoid appearance (OR = 4.2) and non-peripheral "washout" (OR = 0.2) were significant independent predictors of CK19-positive HCCs.Targetoid appearance and absence non-peripheral "washout" combined with elevated AFP were useful for differentiating CK19-positive HCCs from CK19-negative HCC.

Rationale & Objective Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. Study Design Multicenter prospective cohort study. Setting & Participants 458 PD patients were enrolled and followed up for 2 years. Predictors Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. Outcomes The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. Analytical Approach Multivariable linear regression models. Results The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (β values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. Limitations A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. Conclusions In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

Hemiplegic gait is the most common sequela of stroke. Patients with hemiplegic gait are at a risk of falling because of poor balance. The theory of cognitive-motor networks paved the way for a new field of research. However, the mechanism of the relationship of cognition with gait or posture control networks is unclear because of the dynamic characteristics of walking and changing postures. To explore differences in the balance function and fall risk between patients with and without cognitive impairment after stroke, we utilized the Berg balance scale, Timed “Up and Go” test, and 10 m walking test. Patients were divided into two groups: the observation group (16 patients, female 6 and male 10), comprising patients with cognitive impairment after stroke, and the control group (16 patients, female 7 and male 9), comprising patients without cognitive impairment after stroke. We found that patients with cognitive impairment had worse balance function and a higher risk of falls. They needed a longer time to turn around or sit down. Our findings indicated that posture control in turning around and sitting down required more cognitive resources in daily life.

The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), known as neural melanocortin receptors, have been implicated to be critical components of the hypothalamic leptin-melanocortin pathway and related to obesity pathogenesis. In contrast to extensive evidence from physiologic, biological, genetic studies demonstrating that MC4R is a critical regulator in obesity, whether MC3R mutation causes obesity is still controversial. In the present study, we screened for coding variants in the MC3R gene of 176 obese individuals (mean BMI 34.84 ± 0.19 kg/m2) and 170 lean controls (mean BMI 20.70 ± 0.08 kg/m2) to assess the prevalence of MC3R mutations in a Chinese cohort. Two novel mutations, A33D (c.C98 > A) and A259T (c.G775 > A), were identified in two subjects with morbid obesity, respectively. A259T was also identified in the carrier's sibling. In vitro functional studies showed that A33D was defective in the cAMP signaling pathway, whereas A259T MC3R had defective maximal binding and cAMP generation in response to NDP- and α-MSH, likely due to decreased cell surface expression. In addition, we showed that A33D and A259T were biased receptors and defect in constitutive activation of ERK1/2 signaling through MC3R might be a cause for morbid obesity. Our sequencing and co-segregation studies combined with comprehensive functional analysis demonstrated that A259T might be predisposing to obesity. Further investigations in larger cohorts will be needed in order to define this association and the specific phenotypic characteristics resulting from these mutations.

Background As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women. Methods and findings In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children’s Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups. Conclusions In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation. Trial registration Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study)., He-Feng Huang and colleagues describe outcomes for infants born to women with COVID-19 early in the outbreak in China., Author summary Why was this study done? Previous studies suggest COVID-19 infections in pregnant women are not more severe than in women of similar age. However, little is known about the outcome of neonates born to COVID-19-infected women. What did the researchers do and find? We analyzed the clinical features of all pregnant women with COVID-19 infection delivered in 2 of the 5 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and their neonates. Among the 30 neonates born to 29 pregnant COVID-19-infected women (1 set of twins), 5 were diagnosed as having COVID-19 (2 confirmed and 3 suspected), and the other 12 neonates presented radiological features of pneumonia, but none were diagnosed with pneumonia. Three neonates developed necrotizing enterocolitis, although none of them were premature. What do these findings mean? A considerable number of, but not all, neonates born to COVID-19-infected women developed COVID-19 (5/30) or had pneumonia-like radiological features (17/30). Intrapartum precaution should not be underestimated, and intrauterine transmission should be considered based on current evidence. Term neonates born to COVID-19-infected women are vulnerable to develop necrotizing enterocolitis.

Neuronal intranuclear inclusion disease is a rare hereditary neurodegenerative disease characterized by localized eosinophilic intracytoplasmic inclusion bodies in cells of the nervous system and internal organs. This disorder is frequently missed or misdiagnosed, as there is significant heterogeneity of its clinical presentation. Recently, genetic sequencing has revealed complex links between neuronal intranuclear inclusion disease and other neurodegenerative diseases, potentially explaining the diversity of clinical manifestations. Herein, we describe the case of a 68-year-old male Chinese patient who was initially diagnosed with Parkinson's disease based on classic symptomatology and ¹²³I-metaiodobenzylguanidine scintigraphy results and was subsequently treated with oral methyldopa for 3 years. He developed a paroxysmal tic before he presented to our hospital for treatment after a convulsive seizure. Brain magnetic resonance imaging identified signal hyperintensity at the corticomedullary junction on diffusion-weighted imaging. Skin biopsy results and genetic testing confirmed a revised diagnosis of neuronal intranuclear inclusion disease. This report highlights that patients clinically diagnosed with Parkinson's disease may actually be in the early stages of neuronal intranuclear inclusion disease, suggesting that patients with suspected Parkinson's disease should also be screened for this disease.

Objective To forecast the future burden and its attributable risk factors of infective endocarditis (IE). Method We analyzed the disease burden of IE and its risk factors from 1990 to 2019 using the Global Burden of Disease 2019 database and projected the disease burden from 2020 to 2030 using a Bayesian age-period-cohort model. Results By 2030, the incidence of IE will increase uncontrollably on a global scale, with developed countries having the largest number of cases and developing countries experiencing the fastest growth. The affected population will be predominantly males, but the gender gap will narrow. The elderly in high-income countries will bear the greatest burden, with a gradual shift to middle-income countries. The incidence of IE in countries with middle/high-middle social-demographic indicators (SDI) will surpass that of high SDI countries. In China, the incidence rate and the number of IE will reach 18.07 per 100,000 and 451,596 in 2030, respectively. IE-associated deaths and heart failure will continue to impose a significant burden on society, the burden on women will increase and surpass that on men, and the elderly in high-SDI countries will bear the heaviest burden. High systolic blood pressure has become the primary risk factor for IE-related death. Conclusions This study provides comprehensive analyses of the disease burden and risk factors of IE worldwide over the next decade. The IE-associated incidence will increase in the future and the death and heart failure burden will not be appropriately controlled. Gender, age, regional, and country heterogeneity should be taken seriously to facilitate in making effective strategies for lowering the IE disease burden.

Background Posterior capsular opacification (PCO) is the main complication after intraocular lens (IOL) implantation in cataract surgery, which is the result of lens epithelial cell (LEC) adhesion, proliferation and migration on the IOL and at the lens capsule interface. Hydrophilic surface modification, such as surface heparinization, decreases the cell adhesion, which has been commercialized and used clinically. However, clinical long-term observation results show no significant difference between the pristine and heparinized IOLs. Methods To prevent PCO over the long time span, we modified the IOLs with an antiproliferative drug-loaded hydrophilic coating. The antiproliferative drug doxorubicin (DOX)-incorporated chitosan (CHI) nanoparticle was fabricated by sodium tripolyphosphate (TPP) gelation. Such antiproliferative drug-loaded CHI-TPP-DOX nanoparticles (CTDNP) were used as one of the building blocks to prepare polyelectrolyte multilayer with heparin (HEP) via layer-by-layer assembly, obtaining (HEP/CTDNP)n multilayers. The assembly process was characterized by quartz crystal microbalance with dissipation (QCM-D). The drug release behavior of the coating was investigated by ultra-HPLC (UPLC). In vitro cell experiments were carried out to monitor the effects of multifunctional coatings on cellular adhesion, proliferation and migration. And the intraocular implantation was performed on rabbits to evaluate the in vivo PCO inhibitory effect of such surface-functionalized IOLs. Results The positively charged CTDNP was successfully prepared by ionic gelation. The QCM-D results indicate the successful preparation of the (HEP/CTDNP)n multilayer film. Drug release profiles showed that surface-multifunctionalized IOL had drug-sustained release properties. In vitro cell culture results showed significant inhibition of adhesion, proliferation and migration of LECs after surface modification. The in vivo results showed that the IOLs with multifunctionalized surface can effectively reduce the posterior hyperplasia and Soemmering’s ring (SR) formation. Conclusion These findings suggested that such multifunctionalized drug-eluting IOLs can effectively reduce the posterior hyperplasia and SR formation when intraocular implantation has a major impact on reducing PCO incidence. Thus they have a great potential in improving patient vision recovery and maintenance., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/selJKG6NMZk

Non-motor symptoms (NMS) are important prodromal characteristics of Parkinson's disease (PD). However, the incidence of NMS in first-degree relatives, such as siblings of PD patients, is still unknown.A total of 98 PD patients of the Affiliated Hospital of Yangzhou University were recruited; 210 siblings of these patients were included in a first-degree relatives (FDR) group and 250 healthy individuals were included in a control group. Various scales were used to assess NMS, including depression, anxiety, cognitive function, sleep status, constipation, daytime sleepiness, Rapid-Eye-Movement Sleep Behavior Disorder (RBD), and Restless Legs Syndrome (RLS).NMS were more common in the PD group than the control group. The incidence of anxiety (OR = 3.434, 95%CI: 2.058-5.731, P 0.001), depression (OR = 2.438, 95%CI: 1.289-4.609, P = 0.005), and RBD (OR = 4.120, 95%CI: 1.897-8.945, P 0.001) was higher in the FDR group than the control group. There were non-significant differences in constipation, cognitive impairment, sleep disorder, daytime sleepiness, and RLS between the two groups. The incidence of RLS in FDR of PD with an age of onset60 years was higher than in the controls (OR = 2.273, 95%CI: 1.107-4.667, P = 0.023).Siblings of PD are more likely to suffer from anxiety, depression and RBD than the general population. RLS is more common in siblings of PD with onset age60 than in the general population. It is speculated that PD patients and their siblings have common pathogenic genetic factors and early living environment for neurodegeneration.

Periprosthetic osteolysis belongs to osteolytic diseases, which often occur due to an imbalance between osteoclast and osteoblast number or activity. Fraxetin, a natural plant extract, inhibits osteoblast apoptosis and has therapeutic potential for treating osteolytic diseases. However, data pertaining to the effects of fraxetin on osteoclasts are limited. In the present study, it was demonstrated that the inhibition of osteoclastogenesis by fraxetin had an important role on the therapy of titanium particle‑induced osteolysis in vivo. In addition, fraxetin was demonstrated to suppress receptor activator of nuclear factor‑κB ligand (RANKL)‑mediated osteoclast differentiation and bone resorption in vitro in a dose‑dependent manner. Fraxetin inhibited osteoclast differentiation and function through the suppression of p38 signaling and subsequently, the suppression of osteoclast‑specific gene expression, including tartrate‑resistant acid phosphatase, nuclear factor of activated T‑cells, cytoplasmic 1, and cathepsin K. In conclusion, fraxetin administration may have potential as a treatment method for periprosthetic osteolysis and other osteolytic diseases.

Essential hypertension is a leading global public health issue, billions of people suffered from it every year. Recently, multiple evidence suggests that DNA methylation play an important role in regulating blood pressure. Here, we tested the risk for essential hypertension conferred by single nucleotide polymorphisms (SNPs) within DNA methyltransferase 1 (DNMT1). Three loci (rs2228611, rs2228612, and rs16999593) were selected to be analyzed in 3410 cases and 1307 normal controls in southern Chinese aged 60 or above. No significant association with essential hypertension was observed for rs2228612 and rs16999593. A higher risk of essential hypertension was found in the minor A allele of rs2228611 in the codominant and recessive model (P < 0.05). After stratified by sex, this association was found in male but not female. Furthermore, this difference was abolished after BMI adjustment in the whole population and reduced in male. In addition, the mutation rate of rs2228611 was higher in the obesity group compared with the normal weight group of male. Intriguingly, rs2228611 was also a risk factor of essential hypertension in normal weight male. These findings indicated that rs2228611 might contribute to male hypertension via BMI-dependent mechanisms in obesity male and BMI-independent mechanisms in normal weight male.

BACKGROUND Waist-to-height ratio (WHtR) is proposed as a simple and effective screening tool for abdominal obesity and cardiovascular disease risk factors. The present study examined the profiles of blood pressure (BP) among children and adolescents categorized by WHtR cutoffs. PATIENTS AND METHODS A total of 28 074 (14 015 boys and 14 059 girls) students aged 7-17 years participated in the study. Height, waist circumference and BP of all patients were measured, and WHtR was calculated. Relatively high blood pressure (RHBP) status was defined as systolic BP and/or diastolic BP of at least the 95th percentile for age and sex. All patients were divided into three groups (low, moderate and high) according to their WHtR. BP level and the prevalence of RHBP among the three groups were compared. RESULTS In both boys and girls, significant differences in BP level and the prevalence of RHBP were observed among the three groups (P

miR-1271 is a multifunctional post-translational modulator, which is involved in several diseases. However, the association between microRNA (miR)‑1271 and fibronectin 1 (FN1) remains to be fully elucidated in neuroglioma. In the present study, it was hypothesized that a post‑translational mechanism of miR‑1271 regulates the expression of FN1 in the progression of neuroglioma. The present study aimed to investigate the clinical significance and underlying molecular mechanisms of miRNA‑1271 in the development of glioma. The miR‑1271 levels in glioma tissues and cell lines were assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). miR‑1271 mimics and inhibitors were transfected to gain or loss of miR‑1271 function. Cell proliferation was analyzed by using an MTT assay. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The mRNA and protein levels were assessed by RT‑qPCR and western blotting. The results showed that miR‑1271 was downregulated in glioma tumor tissues and cell lines. In addition, it was demonstrated that low levels of miR‑1271 in patients with glioma were correlated with low survival rate. In vitro, the cell viability was significantly suppressed following transfection with miRNA‑1271 mimics and increased following transfection with the miRNA‑1271 inhibitor. The miRNA‑1271 mimics induced cell apoptosis and the miRNA‑1271 inhibitor suppressed cell apoptosis in H4 and U251 cell lines. Furthermore, the 3'‑untranslated region of FN1 was bound by miR‑1271. Therefore, it was concluded that miR‑1271 inhibited glioma cell growth by targeting FN1, and a low level of miR‑1271 in glioma tumor tissues was associated with lower survival rates in patients with glioma.

Background Waist-to-height ratio (WHtR) is proposed as a simple, valid and convenient measure of abdominal obesity and health risks in practice. The present study examined the distribution of nutritional status among children and adolescents categorized by WHtR cut-offs. Methods A total of 30,459 students (15,249 boys and 15,210 girls) aged 7–18years participated in the study. Height, weight and waist circumference (WC) of all subjects were measured, body mass index (BMI) and WHtR were calculated. The grades of nutritional status (thinness, normal weight, overweight and obesity) was defined by the international BMI cut-offs. All subjects were divided into three groups (low, moderate and high) according to their WHtR, BMI level and the distribution of nutritional status among the three groups were compared. Results In both boys and girls, significant differences in BMI level and the nutritional status were observed among the three groups. Children and adolescents aged 7–18years in the ‘high WHtR group' (≥0.5) had higher BMI than those in the ‘low WHtR group' ( 2 for boys and 5.24–9.51kg/m 2 for girls. ‘low WHtR group' had higher prevalence of thinness, and ‘high WHtR group' had higher prevalence of overweight and obesity. The optimal distribution of nutritional status is found in the ‘moderate WHtR group' (between 0.4 and 0.5) with the highest proportion of normal weight and low prevalence of thinness and obesity. Conclusion WHtR is associated with nutritional status, which could be an indicator of nutritional status and early health risk. It is necessary to develop optimal boundary values in the future.

Background A study to evaluate the prevalence of uric acid (UA) nephrolithiasis with dual-energy CT (DECT) and explore the risk factors for kidney stones in primary gout patients. Methods Eighty-four consecutive gout patients underwent urinary tract ultrasonography or DECT to confirm the existence of kidney stones. Urine and blood samples were also taken for laboratory analysis. Results Forty-one subjects (48.8%) had nephrolithiasis diagnosed; 38 had a kidney stone. Thirty-two of the 38 patients underwent a DECT scan, and 27 patients had nephrolithiasis in DECT. Among them, 63.0% (17/27) and 14.8% (4/21) of the patients had pure UA and UA-based mixed stone, respectively, and 22.2% (6/27) had a non-UA stone. Those with nephrolithiasis suffered from more frequent acute attacks and had longer disease durations of gout. At least one urine biochemical abnormality was found in 81% of patients. Forty-four (55.0%) patients presented hypomagnesuria. Forty-three (51.8%) patients had low urine volume. Unduly acidic urine (UAU) was present in 36 patients (44.4%). Hyperuricosuria was only found in ten (12.2%) patients. In comparison to the non-lithiasic group, the lithiasic group was more likely to have a UAU. Binary logistic regression showed that female gender was a protective factor, while disease duration of gout and low urine pH were risk factors for nephrolithiasis. Conclusion Our results indicated that nephrolithiasis, especially UA stones, were more common than previous reports in gout patients indicated, and that disease duration of gout, and low urine pH, were risk factors for nephrolithiasis.

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations. Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing). Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher trough SDC (1.20 ± 0.50 ng/mL) than recommended trough SDC for heart failure patients. Trough SDC was not significantly influenced by mutations of OATP1B1 388A>G (P = .890), 521T>C (P = .054), and OATP1B3 699G>A (P = .854). Patients with OATP1B1 521T>C mutant-type carrier had slightly higher trough SDC (0.98 ± 0.53 ng/mL) than those with wild-type carrier (0.74 ± 0.40 ng/mL) when they have repaired renal function. Heart failure patients with severe renal dysfunction (GFRC mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring.

Background: Patients with chronic kidney disease experience a high burden of sleep disorders, and there are associations between sleep disorders and cognitive impairment. Objectives: Based on our previous cross-sectional survey on cognitive impairment in peritoneal dialysis, we further explored the relationship between sleep disorders and cognitive impairment, and predictors for declining cognitive function. Method: We conducted a multicenter prospective cohort study enrolling 458 clinically stable patients on peritoneal dialysis who were then followed up for 2 years.Demographic data, comorbidities, depression, and biochemistry data were collected at baseline. Sleep disorders including insomnia, restless legs syndrome, sleep apnea syndrome, excessive daytime sleepiness, possible narcolepsy, sleep walking and nightmares, and possible rapid eye movement behavior disorders were assessed using a panel of specific sleep questionnaires at baseline and in a second survey. Global cognitive function was measured at baseline and in a second survey, using the Modified Mini-Mental State Examination. Specific cognitive domains were evaluated using Trail-Making Test Forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status were used to asses immediate and delayed memory, visuospatial skills, and language ability. Results: Sleep disorders were common among peritoneal dialysis patients. The prevalence of cognitive impairment evaluated by the Modified Mini-Mental State Examination (3MS) increased from 19.8 to 23.9%. Possible narcolepsy was associated with decreased Modified Mini-Mental State Examination scores at baseline. During follow-up, sleepwalking and nightmares were associated with higher risks of declined delayed memory in the longitudinal study. Conclusions: Possible narcolepsy was associated with general cognitive dysfunction, and sleep walking and nightmares were risk factors for impaired delayed memory.

To investigate the mechanisms through which myocyte large-conductance CaMiddle cerebral arteries (MCA) were obtained from 8-week-old male Wistar rats after anaesthetized. Middle cerebral arterial smooth muscle cells were enzymatically isolated. Whole cell recording mode of patch clamp technique was used to measure the current density of BK① Melatonin markedly increased the whole-cell BKMelatonin mediates vasodilation of MCA through the activation of BK

Previous studies compared ocular aberration and visual quality after small-incision lenticule extraction (SMILE) and Q value-guided femtosecond laser-assisted in situ keratomileusis (Q-FS-LASIK), but anterior corneal surface aberration properties are poorly known. This study aimed to compare the changes in anterior corneal surface aberration after SMILE versus Q-FS-LASIK. This was a prospective, observational cohort study. Patients with myopia and myopic astigmatism underwent SMILE or Q-FS-LASIK at Hangzhou MSK Eye Hospital between January 2015 and November 2015. High order aberration (HOA), primary spherical aberration (PSA), primary coma aberration (PCA), primary vertical coma aberration (PVCA), and primary horizontal coma aberration (PHCA) were assessed using pre- and postoperative Sirius scanning. Both surgery were associated with significant increases in postoperative HOA, PSA, and PCA (both groups P .05). In the Q-FS-LASIK group (n = 73), the variations in HOA and PCA were no longer significant after postoperative day 1 (P > .05). In the SMILE group, the 3-month changes in PCA were not correlated with spherical, spherical equivalent (SE), and spherical plus cylinder measurements. Cylinder measurements were not correlated with HOA, PSA, and PCA. In the Q-FS-LASIK group, the 3-month changes in PCA correlated with spherical, SE, and spherical plus cylinder measurements. Both SMILE and Q-FS-LASIK resulted in an increase in HOA, PSA, and PCA at postoperative day 1, but Q-FS-LASIK introduced lower HOA and showed better stability. Spherical measurement was related to PSA.

Patient empowerment has been shown to have some positive impacts on self-efficacy, self-esteem, and recovery. However, information about the empowerment needs of patients after a percutaneous coronary intervention is scarce. The aim of this study was to develop a Chinese-language instrument to measure empowerment needs of such patients. The initial instrument was generated based on a literature review and interviews with patients after a percutaneous coronary intervention procedure. Content validity was tested with a panel of experts using the Delphi method. In total, 226 patients were recruited for psychometric tests using the revised instrument. Expert authority coefficient was 0.92, and content validity index was 0.95. The internal consistency reliability was demonstrated by Cronbach's α coefficients (0.86 for the total score, 0.66-0.74 for the dimensions). The newly developed 19-item, five-dimension instrument has shown satisfactory validity (face/content validity and construct validity) and internal consistency reliability. The instrument could help clinical nurses who have close contact with patients after a percutaneous coronary intervention to gain a better understanding of their empowerment needs and could help develop appropriate health education to address such needs.

Objectives: Our research investigated the relationship between childhood leukemia and breastfeeding in the P. R. of China. Methods: We conducted a retrospective case-control study from March 2008 to April 2017 at the Children’s Hospital of Zhejiang University, Zhejiang province, P. R. of China, which reviewed 958 children who had been diagnosed with leukemia in case group and 785 healthy children in control group. Data were obtained from medical records, and if the medical records were incomplete, we called mothers of children by phone to complete the data. Results: Breastfeeding reduces the risk of childhood leukemia; the effect is greater, if feeding continued for 7–9 months (p = 0.002). In addition, we suggest that some factors such as maternal age, smoking during pregnancy, abortion history, genetic factors, parents use of hair dye, and the history of using birth control pills before pregnancy can increase the risk of childhood leukemia. Conclusions: This study indicates that promoting breastfeeding for 7–9 months may help lower the childhood leukemia incidence. Our study firstly demonstrates that breastfeeding has protective effects against childhood leukemia in the P. R. of China. Abbreviations: ALL: Acute lymphocytic leukemia; AML: Acute myeloid leukemia

PURPOSE: To develop a dual-RF, dual-echo, three-dimensional ultrashort echo-time (UTE) pulse sequence and bone-selective image reconstruction for rapid high-resolution craniofacial MRI. METHODS: The proposed pulse sequence builds on recently introduced dual-RF UTE imaging [Johnson et al, MRM, 2017]. While yielding enhanced bone specificity by exploiting high sensitivity of short T(2) signals to variable RF pulse widths, the parent technique exacts a two-fold scan time penalty relative to standard dual-echo UTE. In the proposed method, the parent sequence’s dual-RF scheme was incorporated into dual-echo acquisitions while radial view angles are varied every pulse-to-pulse repetition period. The resulting four echoes (two for each RF) were combined via view-sharing to construct two sets of k-space datasets, corresponding to short and long TEs, respectively, leading to a two-fold increase in imaging efficiency. Further, by exploiting the sparsity of bone signals in echo-difference images, acceleration was achieved by solving a bone-sparsity constrained image reconstruction problem. In vivo studies were performed to evaluate the effectiveness of the proposed acceleration approaches in comparison to the parent method. RESULTS: The proposed technique achieves 1.1 millimeter isotropic skull imaging in 3 min without visual loss of image quality, compared to the parent technique (scan time = 12 min). Bone-specific images and corresponding 3D renderings of the skull were found to depict the expected craniofacial anatomy over the entire head. CONCLUSION: The proposed method is able to achieve high-resolution volumetric craniofacial images in a clinically practical imaging time, and thus may prove useful as a potential alternative to computed tomography.

Background Depression has been recognized as a risk factor for cognitive impairment (CI) from cross-sectional datasets. This multicenter prospective study investigated the association between depression and cognitive decline in peritoneal dialysis (PD) patients. Methods This multicenter prospective cohort study included 458 PD patients who were followed up for 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function, Trail-Making Tests A and B for executive function, subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skill, and language ability. Depression was assessed using Zung's Self-Rating Depression Scale. Results During the 2-year follow-up, patients with moderate/severe depression at baseline showed a significant decline in global cognitive function (80.5 ± 15.2 vs 76.6 ± 15.5, p = 0.008), while patients without depression or with mild depression kept a stable global cognitive function. In the meantime, patients without depression showed significant improvements in immediate memory, visuospatial skill, and language ability. However, no significant improvement in these parameters was shown in depression groups. In multivariable linear regression analysis, depression at baseline was a significant predictor of worsening global cognitive function, whether depression was analyzed as a continuous variable (odds ratio [OR] = -0.14, 95% confidence interval [CI] -0.27, -0.01, p = 0.031) or a rank variable (OR = -1.88, 95% CI -3.30, -0.45, p = 0.010). Moreover, higher depression score or more severe depression degradation was significantly associated with decline of immediate memory, delayed memory, and language skill. Conclusion Depression was a significant risk factor for worsening of CI in PD patients.

BACKGROUND BMI and waist circumference (WC) are two commonly used measurements for defining general and central obesity. The present study examined the profiles of blood pressure (BP) among children and adolescents categorized by BMI and WC in Shandong, China. PARTICIPANTS AND METHODS A total of 38 810 students (19 453 boys and 19 357 girls) aged 7-17 years participated in this study. Height, weight, WC, and BP of all participants were measured, and BMI was calculated. Relatively high BP status was defined as systolic BP and/or diastolic BP ≥95th percentile for age and sex. All individuals were classified into four groups (Q1-Q4) according to the age-specific and sex-specific quartiles of BMI and WC; the BP level and the prevalence of relatively high BP among the four groups were compared. RESULTS In both boys and girls, significant differences in BP level and the prevalence of relatively high BP were observed among the four groups categorized by BMI and WC separately (P

Liver fibrosis is the accumulation of extracellular matrix proteins and is a feature of most chronic liver diseases (CLDs) (1). Studies have demonstrated that fibrosis is reversible at early stages (2, 3), and causal treatments improve liver function (4). Because of the great risk of liver cirrhosis, hepatocellular carcinoma (HCC), and other complications in patients with liver fibrosis, accurate assessment of the liver fibrosis stage and early detection of early cirrhosis are important for judging the prognosis and planning treatment (5). Furthermore, the severity of fibrosis has been associated with remnant liver functional reserve after hepatectomy for HCC (6). A noninvasive tool that would enable us to preoperatively evaluate the severity of liver fibrosis would be beneficial for a more risk-adapted treatment strategy. Liver biopsy is commonly considered to be the gold standard for grading liver fibrosis; however, biopsy is considered impractical for evaluating disease progression or response to treatment because of its invasiveness, interobserver variability, sample errors, patients’ acceptance, and complications such as bleeding, infection, and pain (7–10). Consequently, a noninvasive and feasible method for assessing the liver fibrosis stage is required. Conventional axial imaging techniques have limited value for evaluating liver fibrosis. Recently, several noninvasive methods have been assessed, including laboratory tests, ultrasound transient elastography (11), and magnetic resonance imaging (MRI)-based techniques (e.g., magnetic elastography, diffusion-weighted imaging [DWI], perfusion, gadoxetic acid-enhanced MRI, and susceptibility-weighted imaging [SWI]) (12–21). SWI was demonstrated to be feasible for abdominal imaging and could utilize phase information to enhance susceptibility effects that were caused by iron in cirrhosis and HCC (22, 23). In theory, increased iron content of the liver and secondary changes manifesting in progressive collagen deposition are important background alterations in the development of liver fibrosis (24). Balassy et al. (21) reported that by measuring the mean values of signal intensities and using a corrected liver-to-muscle ratio, SWI might be used as an alternative technique to assess the severity of hepatic fibrosis. However, they did not consider the heterogeneity of fibrotic liver parenchyma. Image texture is a sensitive characteristic for assessing pathology, and texture analysis is a method that can provide more information regarding the image texture features that may be ignored by visual evaluation (25). A histogram is a useful tool in hepatic texture analysis for depicting the distribution of signal intensity levels (26), which can reflect the heterogeneity of pathologic changes. Kim et al. (27) demonstrated that histogram analysis of gadoxetic acid-enhanced hepatobiliary phase MRI could be useful in depicting enhancement heterogeneity, which is representative of the liver fibrosis stage (27). We hypothesized that the fibrotic liver had different heterogeneities of iron deposition and secondary changes in different fibrosis stages, which might be detected by histogram analyses of SWI. Thus, we aimed to evaluate whether histogram analysis of SWI could quantify liver fibrosis stages and assess whether different echo times (TEs) of SWI could affect the quantification of SWI histogram analyses.

Previous studies have demonstrated that polypeptides extracted from scorpion venom (PESV) inhibited cell proliferation in several tumors, however, the effect on dysfunctional and exhausted natural killer cells which contribute to tumor escape from immune surveillance remain to be elucidated. In this study, we determined the effect of PESV on NK infiltration into H22 cells orthotopic transplantation tumors and on the expression of MHC class I chain-related proteins A (MICA) in HepG2 cells. We found that tumor growth in mice was significantly inhibited by PESV and the survival time of tumor-bearing mice treated with PESV was significantly prolonged. Moreover, levels of tumor-infiltrating NK cells, NKG2D protein, perforin and granzyme B mRNA were significantly increased in the group treated with PESV compared with the tumor-bearing control group. In addition, In addition, up-regulation of MICA by PESV enhances the susceptibility of HepG2 cells to NK lysis in vitro. These results indicate that the inhibitory effects of PESV on hepatic carcinoma are likely mediated by up-regulation of NK cell activity via the MICA-NKG2D pathway.

Childhood overweight and obesity has increased dramatically during the past decades, both in developing and developed countries. The present study examined the prevalent trends in overweight and obesity among rural children and adolescents over the past 29 years (1985-2014) in Shandong, China.Data for this study were obtained from six cross-sectional surveys (1985, 1995, 2000, 2005, 2010 and 2014) of schoolchildren in Shandong Province, China. A total of 27,840 rural students aged 7-18 years were included in this study. Body mass index cut-off points recommended by the Working Group on Obesity in China (WGOC), the International Obesity Task Force (IOTF) and the World Health Organization (WHO) were used to define overweight and obesity.The prevalence of overweight and obesity has been increasing continually in rural areas over the past 29 years (1985-2014). Using WGOC criteria, for boys, the prevalence of overweight and obesity increased from 0.74% and 0.03% in 1985 to 16.35% and 17.20% in 2014, and for girls it increased from 1.45% and 0.12% in 1985 to 13.91% and 9.11% in 2014, respectively. A similar increasing trend was observed by IOTF and WHO criteria.The prevalence of overweight and obesity among children and adolescents in Shangdong rural areas increased rapidly between 1985 and 2014. Rural areas should not be neglected in obesity intervention, policy-makers and experts should pay more attention to the new tendency.

Background Given that China has free universities dedicated solely to the elderly, such universities may be the perfect place to provide large numbers of elderly with a systematic program of self-management. Yet, testing health applications in this location has not occurred, partly because time-consuming training is required before applications can be used. Objective This study aimed to develop and implement a smartphone training program for the elderly and to confirm the effects on smartphone competency and quality of life. Methods A randomized controlled trial was conducted. Participants were randomly assigned to either the intervention group or the wait-list control group. A smartphone operation manual was provided to all participants. The intervention group received the smartphone training program once a week for 20 weeks. After the study was finished, participants in the wait-list control group were permitted to undergo the smartphone training program. Results Of the 344 participants were randomized at the elder university in Huzhou. After 20 weeks of the intervention, the intervention group showed significant improvement in smartphone usage competency (except health applications) and quality of life relative to the wait-list control group (P Conclusion This study confirmed the effectiveness of the smartphone training program in the elder university setting. However, further research is needed to strengthen the intervention in the area of health applications.

Background: LMNA-related muscular dystrophy can manifest in a wide variety of disorders, including Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), and LMNA-associated congenital muscular dystrophy (L-CMD). Muscle magnetic resonance imaging (MRI) has become a useful tool in the diagnostic workup of patients with muscle dystrophies. This study aimed to investigate whether there is a consistent pattern of MRI changes in patients with LMNA mutations in various muscle subtypes. Methods: Twenty-two patients with LMNA-related muscular dystrophies were enrolled in this study. MRI of the thigh and/or calf muscles was performed in them. The muscle MRI features of the three subtypes were compared by the Mann-Whitney U-test. The relationship between the clinical and MRI findings was also investigated by Spearman's rank analyses. Results: The present study included five EDMD, nine LGMD, and eight L-CMD patients. The thigh muscle MRI revealed that the fatty infiltration of the adductor magnus, semimembranosus, long and short heads of the biceps femoris, and vasti muscles, with relative sparing of the rectus femoris, was the predominant change observed in the EDMD, LGMD, and advanced-stage L-CMD phenotypes, although the involvement of the vasti muscles was not prominent in the early stage of L-CMD. At the level of the calf, six patients (one EDMD, four LGMD, and one L-CMD) also showed a similar pattern, in which the soleus and the medial and lateral gastrocnemius muscles were most frequently observed to have fatty infiltration. The fatty infiltration severity demonstrated higher scores associated with disease progression, with a corresponding rate of 1.483 + 0.075 × disease duration (X) (r = 0.444, P = 0.026). It was noteworthy that in six L-CMD patients with massive inflammatory cell infiltration in muscle pathology, no remarkable edema-like signals were observed in muscle MRI. Conclusions: EDMD, LGMD and advanced-staged L-CMD subtypes showed similar pattern of muscle MRI changes, while early-staged L-CMD showed somewhat different changes. Muscle MRI of L-CMD with a muscular dystrophy pattern in MRI provided important clues for differentiating it from childhood inflammatory myopathy. The fatty infiltration score could be used as a reliable biomarker for outcome measure of disease progression.

Regulation of prostate cancer by androgen and androgen receptor (AR), and blockade of AR signaling by AR antagonists and steroidogenic enzyme inhibitors have been extensively studied. G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate almost all physiological processes. Nearly 40% of FDA-approved drugs in the market target GPCRs. A variety of GPCRs that mediate reproductive function have been demonstrated to be involved in the regulation of prostate cancer. These GPCRs include gonadotropin-releasing hormone receptor, luteinizing hormone receptor, follicle-stimulating hormone receptor, relaxin receptor, ghrelin receptor, and kisspeptin receptor. We highlight here GPCR regulation of prostate cancer by these GPCRs. Further therapeutic approaches targeting these GPCRs for the treatment of prostate cancer are summarized.

B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses. This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice. Normal mice were divided into control, short hairpin RNA (shRNA) scramble, and shRNA BATF groups. HBV transgenic mice were divided into control, entecavir, shRNA scramble, entecavir + vector control, entecavir + shRNA scramble, shRNA BATF, and entecavir + shRNA BATF groups. Serum concentrations of AST, ALT, HBV-DNA, BATF, IL-17, and IL-22 and Th17 cell frequencies in the liver were compared among the groups. Correlations of serum HBV surface antigen (HBsAg), e-antigen (HBeAg), and core antigen (HBcAg) concentrations with BATF mRNA expression and the proportion of Th17 cells in the livers of HBV transgenic mice were also analyzed. Serum AST, ALT, BATF, IL-17, and IL-22 concentrations and Th17 cell proportions were higher in HBV transgenic mice relative to normal controls. Positive correlations of the HBcAg concentration with BATF mRNA and the proportion of Th17 cells were observed in HBV transgenic mice. BATF interference reduced the proportion of Th17 cells and serum IL-17 and IL-22 concentrations and led to obvious downregulation of AST, ALT, BATF, IL-17, and IL-22 expression and a reduced proportion of Th17 cells when combined with entecavir. HBV markedly upregulated BATF expression and promoted Th17 cell activation. By contrast, BATF interference significantly impeded the proliferation of Th17 cells and secretion of IL-17 and IL-22 while alleviating hepatic lesions.

Background: For patients with a brain metastasis (BM), systemic therapy is usually administered after the completion of radiotherapy, especially in cases of multiple BMs. However, the role of systemic therapy in patients with a limited number of BMs is not clear. Therefore, we conducted a retrospective study to explore this question. Methods: Consecutive patients with a pathologically confirmed malignancy and 1–3 intracranial lesions that had been documented within the last decade were selected from the databases of three hospitals in China. Results: A total of 250 patients were enrolled; of them, 135 received radiotherapy alone and 115 received radiotherapy plus systemic therapy. In patients receiving whole-brain radiation therapy (WBRT) as radiotherapy, 28 received WBRT alone and 35 patients received WBRT plus systemic therapy. Of the patients treated with stereotactic radiosurgery (SRS), 107 received SRS alone and 80 received SRS plus systemic therapy. Multivariate analysis revealed that systemic therapy significantly reduced the risk of mortality compared with radiotherapy alone (hazard ratio [HR] = 0.294, 95% confidence interval [CI] = 0.158- 0.548). Further, when the analysis was conducted in subgroups of WBRT (HR = 0.230, 95% CI = 0.081- 0.653) or SRS (HR = 0.305, 95% CI = 0.127–0.731), systemic therapy still showed the ability to reduce the risk of mortality in patients with BMs. Conclusion: Systemic therapy after either SRS or WBRT radiotherapy may significantly reduce the risk of mortality of patients with 1–3 BMs. Key words: Brain Metastasis; Stereotactic Radiosurgery; Systemic Therapy; Whole-brain Radiation Therapy

Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P < 0.05). Incubation with GDC-0449 or transfection with Smo-siRNA resulted in a significant increase of G1 phase cells compared to controls (P < 0.05). Cell cycle arrest was validated by the significant increase in cyclin D1 and E1 mRNA expression, decrease in cyclin-dependent kinase p21 mRNA expression in Smo-siRNA transfected cells (P < 0.05). Protein expression of cyclin D1 was also downregulated after Smo gene knockdown (P < 0.05). The results suggest that Shh signaling plays an important role in RA-FLSs proliferation in a Smo-dependent manner and may contribute to synovial hyperplasia. Targeting Shh signaling may help control joint damage in patients with RA.

Thinness in children and adolescents poses a considerable public health problem globally, especially in developing countries. The present study examined the prevalence of thinness among children and adolescents in Shandong, China.Data for this study were obtained from a large cross-sectional survey of schoolchildren. A total of 42,348 students (21,248 boys and 21,100 girls) aged 7-18 years participated in this study. Stature and weight of all subjects were measured; body mass index (BMI) was calculated from their stature and weight. International BMI cutoffs were used to define thinness.The overall prevalences of thinness grade 1, grade 2 and grade 3 among children and adolescents aged 7-18 years were 7.74, 1.43 and 0.61 % for boys and 11.51, 2.54 and 1.03 % for girls, respectively; these figures were all significantly higher in girls than in boys (P0.01). Thin children and adolescents had lower stature levels than their counterparts in not thin group in all age groups (7-18 years).The prevalence of childhood thinness is still wide in Shandong Province, and public health and nutritional strategies must give attention to the intervention for thinness, including periodic monitoring, education on pattern of nutrition and healthy dietary behavior.