Bronchiolar adenoma/ciliated muconodular papillary tumour: advancing clinical, pathological, and imaging insights for future perspectives.

Bronchiolar adenoma/ciliated muconodular papillary tumour (BA/CMPT) is a benign peripheral lung tumour composed of bilayered bronchiolar-type epithelium containing a continuous basal cell layer; however, the similarities in imaging and tissue biopsy findings at histopathology between BA/CMPT and malignant tumours, including lung adenocarcinoma, pose significant challenges in accurately diagnosing BA/CMPT preoperatively. This difficulty in differentiation often results in misdiagnosis and unnecessary overtreatment. The objective of this article is to provide a comprehensive and systematic review of BA/CMPT, encompassing its clinical manifestations, pathological basis, imaging features, and differential diagnosis. By enhancing healthcare professionals' understanding of this disease, we aim to improve the accuracy of preoperative BA/CMPT diagnosis. This improvement is crucial for the development of appropriate therapeutic strategies and the overall improvement of patient prognosis.

Factors associated with nocturnal and diurnal glycemic variability in patients with type 2 diabetes: a cross-sectional study.

PURPOSE: There is little information on factors that influence the glycemic variability (GV) during the nocturnal and diurnal periods. We aimed to examine the relationship between clinical factors and GV during these two periods. METHODS: This cross-sectional study included 134 patients with type 2 diabetes. 24-h changes in blood glucose were recorded by a continuous glucose monitoring system. Nocturnal and diurnal GV were assessed by standard deviation of blood glucose (SDBG), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE), respectively. Robust regression analyses were performed to identify the factors associated with GV. Restricted cubic splines were used to determine dose-response relationship. RESULTS: During the nocturnal period, age and glycemic level at 12:00 A.M. were positively associated with GV, whereas alanine aminotransferase was negatively associated with GV. During the diurnal period, homeostatic model assessment 2-insulin sensitivity (HOMA2-S) was positively associated with GV, whereas insulin secretion-sensitivity index-2 (ISSI2) was negatively associated with GV. Additionally, we found a J-shape association between the glycemic level at 12:00 A.M. and MAGE, with 9.0 mmol/L blood glucose level as a cutoff point. Similar nonlinear associations were found between ISSI2 and SDBG, and between ISSI2 and MAGE, with ISSI2 value of 175 as a cutoff point. CONCLUSION: Factors associated with GV were different between nocturnal and diurnal periods. The cutoff points we found in this study may provide the therapeutic targets for beta-cell function and pre-sleep glycemic level in clinical practice.

Effect of clay supplementation on growth performance of broiler chickens: a systematic review and meta-analysis.

1. This review assessed the effect of dietary clay supplementation as a drug and toxin adsorbent on broiler growth performance as a meta-analysis.2. A total of 33 eligible studies were included in the present study after identification and evaluation from online databases. Standardised mean differences (SMD) with corresponding 95% confidence intervals were computed with a fixed-effects model.3. The results indicated that clay supplementation significantly improved broiler daily gain (P < 0.001) and feed conversion ratio (P < 0.001), but did not affect feed intake (P = 0.954). Results of subgroup analysis showed that zeolite clay had the most stable medium improvement effect on FCR, while kaolin had a large effect. In addition, male broilers and Cobb or Ross broilers were more sensitive to the addition of clay, and the best supplemental levels, in general, were 10 g/kg to 30 g/kg.4. Meta-regression analysis showed that clay supplemental level and sex of broilers may be important factors in the effect of clay on ADG and FCR of broilers, respectively. The sensitivity analysis showed high stability of the results and no significant publication bias was found with funnel plot analysis and Egger's or Begg's test (P > 0.05).5. In conclusion, an appropriate addition level is a prerequisite for effective clay application. Kaolin and zeolite clays seem to be more suitable for enhancing broiler growth performance, and the value of clay is amplified in specific broiler breeds.

[Progress in pulmonary enteric adenocarcinoma].

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.

[Clinical characteristics and prognosis of seizures in 75 children with acute lymphoblastic leukemia].

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

[A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection].

Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.

[A study about the epidemiological characteristics of rabies of the cases of medical treatment from a certain hospital in Beijing from 2011 to 2020].

From 2011 to 2020, there were 111 213 cases of rabies exposed people recruited from the rabies immunization clinic of a hospital in Beijing. The monthly distribution of patients in each year was not statistically significant (P>0.05). The distribution of patients showed remarkable seasonality, with the exposure peak from May to October. The ratio of male to female was 1∶1.3. The majority of patients were aged 20-29 years old (39.1%) and in-service personnel (56.5%). Level-Ⅱ wounds (84.2%) were more common than level-Ⅲ wounds (14.9%). The number of visits to level-Ⅲwounds increased rapidly since 2017. The most common injured body part was hand (60.7%). Dogs were the most common animal for injuries (60.6%), followed by cats (32.3%), of which most were host animals (75.5%). The vaccination rate from 2016 to 2020 [49.8% (24 276/48 703)] was significantly higher than that from 2011 to 2015[18.6% (6 559/35 272)](χ²=8597.18, P<0.001).

[Comparison and correlation analysis of sleep parameters between watch-type sleep monitor (Actiwatch) and polysomnography].

OBJECTIVE: With the rapid development of sleep medicine, there are various methods for detecting sleep diseases. This study compared the correlation between the lightweight watch-type sleep monitor (Actiwatch) and the "gold standard" polysomnography (PSG) in the Chinese population, in order to provide a basis for clinical application. METHODS: From August 2018 to December 2019, 121 subjects who simultaneously performed sleep breathing monitoring (PSG) and wearing a watch-type sleep monitor (Actiwatch) in the Sleep Center of Peking University People's Hospital were enrolled. All subjects received PSG and Actiwatch at the same time, and filled out the sleep diary next morning. Monitoring indicators were collected for linear correlation analysis and paired t test to compare the differences. RESULTS: Under low sensitivity conditions, the correlation coefficient of total sleep time (TST) between PSG and Actiwatch was 0.53 (P < 0.05). Paired t test analysis showed that there was no significant difference between the TSTs of Actiwatch and PSG (t=-0.890, P=0.36). According to age stratification, the smaller the age, the stronger the correlation between the TSTs of Actiwatch and PSG, and the coefficient could be up to 0.92 (P < 0.05). Paired t test showed that there was no significant difference between them (t=-1.057, P=0.35). According to the stratification by diagnosis, the correlation coefficient between the TSTs of Actiwatch and PSG in normal PSG group could be as high as 0.79 (P < 0.05), the results of paired t test showed that there was no significant difference between the TSTs of Actiwatch and PSG in normal PSG group (t=-0.784, P=0.44). CONCLUSION: As a wearable home recorder, when the analysis parameters of Actiwatch were set as low sensitivity, PSG and Actiwatch had the highest TST correlation. The younger the age, the stronger correlation between the TSTs of Actiwatch and PSG. The PSG and Actiwatch subjects with normal PSG presentation had a higher TST correlation.

[Utility of the type 3 portable monitor for the diagnosis of sleep disordered breathing in patients with stable heart failure].

Objective: To evaluate the utility of a type 3 portable monitor (PM) at home for the diagnosis of sleep disordered breathing (SDB) in patients with stable congestive heart failure (CHF). Methods: Seventy-six consecutive patients with CHF (61 males, 15 females, mean±standard deviation age (57.0±16.9) years) were enrolled from the sleep center of Peking university People's Hospital during January 2016 to January 2019, and underwent overnight, unattended home sleep apnea testing (HSAT) with a portable monitor followed by an overnight simultaneous polysomnogram (PSG) with in-laboratory portable monitor (in-lab PM) recording within one week. The consistency of apnea hypopnea index (AHI), obstructive sleep apnea index (OAI), central sleep apnea index (CAI) between HSAT and PSG as well as the in-lab PM and PSG were analyzed by Bland-Altman plot; the sensitivity and specificity of PM for the diagnosis of SDB in patients with CHF were evaluated. Results: The number of patients included in the final analysis were 65 in HSAT, 63 in in-lab PM and 65 in PSG. AHI [M(Q1,Q3)] was 26.1 (10.9,40.1) events/h by HSAT, 27.9 (11.3,43.2) events/h by in-lab PM, both were not different from AHI 29.0 (10.2,45.0) events/h by PSG (P>0.05). The AHI, OAI and CAI assessed by HSAT correlated significantly with those by PSG (r=0.892, 0.903, 0.831, P<0.05). Bland-Altman analysis of AHI, OAI, CAI by PSG versus HSAT showed a mean difference of 3.1 events/h, 0.8 events/h, 1.2 events/h; limits of consistency were -15.2 to 21.4 events/h, -9.7 to 11.3 events/h, -10.9 to 13.2 events/h, respectively. Based on a threshold of AHI ≥5 events/h, HSAT had 94.6% sensitivity, 75% specificity, compared to PSG. For detecting Cheyne-Stokes respiration (CSR), a sensitivity of 96.4%,a specificity of 97.2% were achieved, compared to PSG. Conclusion: Type 3 PM can be used to diagnose SDB in patients with CHF.

[Effect of levothyroxine treatment on pregnancy outcomes in euthyroid women with thyroid autoantibody positive: a Meta-analysis].

Objective: To conduct a systematic review of the association of levothyroxine treatment with pregnancy outcomes in euthyroid women who are thyroid autoantibody positive. Methods: Medline, Excerpta Medica (EMBASE), Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Wanfang data and VIP database were searched from inception until Jan. 28, 2020. All published randomized controlled trials assessing the association of levothyroxine treatment with pregnancy outcomes in euthyroid women with thyroid autoantibody-positive were included. STATA 11.0 and RevMan 5.3 softwares were used to perform this Meta-analysis. Results: A total of 6 studies met the inclusion criteria, with 2 188 women randomized. Meta-analysis showed that there was no significantly association between miscarriage (OR=0.85, 95%CI: 0.65-1.11, P=0.234) and preterm birth (OR=0.79, 95%CI: 0.54-1.16, P=0.224) with levothyroxine treatment. Conclusions: Levothyroxine therapy could not reduce the risk of miscarriage and preterm birth in euthyroid women with thyroid autoantibody-positive. Therefore, levothyroxine should be used with caution for these pregnant women.

Association of plasma C-reactive protein with ischaemic stroke: a Mendelian randomization study.

BACKGROUND AND PURPOSE: Elevated C-reactive protein (CRP) is associated with an increased risk of ischaemic stroke (IS). However, the causality of this association is uncertain. The aim is to investigate whether genetically raised plasma CRP concentration levels are associated with IS on the basis of the Mendelian randomization method. METHODS: Based on the National Center for Biotechnology Information single nucleotide polymorphism (SNP) database, the Chinese online genetic database as well as previously published studies, four CRP-associated SNP alleles (rs1130864, rs1205, rs876537 and rs3093059) with minor allele frequency ≥0.15 were selected and the concentration levels of CRP were measured in 378 first-ever IS patients and 613 healthy controls. RESULTS: Three SNPs were chosen and used as instrumental variables. The adjusted odds ratios (ORs) [95% confidence interval (95% CI)] of IS per addition of the modelled allele were 1.07 (0.79-1.45) for rs876537, 0.99 (0.73-1.35) for rs1205 and 1.08 (0.71-1.65) for rs3093059. The OR (95% CI) of IS for plasma CRP ≥2.0 mg/l was 2.19 (1.06-4.53) compared with <2.0 mg/l. The adjusted OR (95% CI) of IS per genetically predicted 10% higher CRP concentration, based on the three SNPs as the instruments, was 1.02 (0.94-1.11). Furthermore, similar results were obtained with adjusted ORs (95% CI) of 1.00 (0.88-1.13) and 1.04 (0.93-1.16), respectively, for large-artery atherosclerosis and small-artery occlusion per genetically predicted 10% higher CRP concentration. CONCLUSIONS: This Mendelian randomization study provides no clear support that elevated CRP concentration is causally associated with the risk of IS.

Diagnostic value of the combined detection of CEA, NSE and IL-18 for lung cancer and their relationship with apoptosis gene Bcl-2.

This study aims to investigate the value of the combined detection of carcinoembryonic antigen (CEA), Neuron-specific enolase (NSE) and the level of Interleukin-18 (IL-18) in the serum in the diagnosis of lung cancer. The correlation between these parameters and the expression levels of B-cell lymphoma-2 (Bcl-2) protein were also studied. Eighty patients with lung cancer were included in the lung cancer group. These patients underwent surgery in the Department of Oncology of Huai'an Second People's Hospital between February 2016 and February 2018. During the same period, another 80 patients with benign lung lesions were registered in the benign lesion group and 80 healthy people were enrolled in the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of CEA, NSE and IL-18. The diagnostic critical value of these factors was used as positive indicator. When CEA, NSE and IL-18 levels were positive at the same time, the combined detection was considered to be positive. WB was used to detect Bcl-2 expression level. We also analyzed the possible correlation between CEA, NSE, IL-18 levels and the Bcl-2 expression levels. The CEA, NSE and IL-18 expression levels in the serum of the lung cancer group were significantly higher than those in the benign lesion and the control groups (p<0.05). The area under ROC curve for CEA, NSE and IL-18 respectively was 0.770 (0.697-0.843), 0.829 (0.767-0.890), 0.721 (0.642-0.800) (p<0.001). IL-18 level was negatively correlated with the level of Bcl-2 mRNA in the tissue (r=-0.380, p<0.001). In conclusion, CEA, NSE and IL-18 have a good auxiliary diagnostic value in patients with lung cancer. The combined detection could improve the sensitivity and specificity of lung can¬cer diagnosis. There was a negative correlation between IL-18 and Bcl-2 levels which suggested a potential inhibitory role of IL-18 on the lung cancer cells apoptosis pathway.

MiR-34a-5p/PD-L1 axis regulates cisplatin chemoresistance of ovarian cancer cells.

Ovarian cancer is the most lethal gynecologic malignancy in women with an increasing number of cases worldwide. Chemoresistance is the main obstacle for ovarian cancer treatment during clinical therapy. Previous studies found that programmed cell death 1 ligand 1 (PD-L1) was associated with chemoresistance of cancer. However, there were little reports about the function of PD-L1 involved in chemoresistance of ovarian cancer. In our study, cisplatin (DDP)-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3/DDP and A2780/DDP) were established. We found that the expression of PD-L1 was increased and miR-34a-5p was decreased in DDP-resistant cells. PD-L1 silencing inhibited chemoresistance of DDP-resistant ovarian cancer cells to DDP, as evidenced by decreased proliferation, G1-phase cell cycle arrest and increased apoptosis. Western blot assay showed that in the presence of DDP, PD-L1 silencing decreased multidrug resistance protein 1 and Cyclin D1 protein levels, whereas increased cleaved-caspase-3 and cleaved-PARP protein levels in these cells. Moreover, we demonstrated that miR-34a-5p negatively regulated the expression of PD-L1 by targeting its 3'-untranslated region. The effects of miR-34a-5p mimic on DDP-treated SKOV3/DDP cells were reversed by the overexpression of PD-L1. Moreover, the tumorigenicity of DDP-resistant ovarian cancer cells in nude mice treated with DDP was attenuated by miR-34a-5p in vivo. The combined data indicate that miR-34a-5p/PD-L1 axis regulates DDP chemoresistance of ovarian cancer cells, providing a deeper insight into the treatment for ovarian cancer.

Selective activation of parvalbumin interneurons prevents stress-induced synapse loss and perceptual defects.

Stress, a prevalent experience in modern society, is a major risk factor for many psychiatric disorders. Although sensorimotor abnormalities are often present in these disorders, little is known about how stress affects the sensory cortex. Combining behavioral analyses with in vivo synaptic imaging, we show that stressful experiences lead to progressive, clustered loss of dendritic spines along the apical dendrites of layer (L) 5 pyramidal neurons (PNs) in the mouse barrel cortex, and such spine loss closely associates with deteriorated performance in a whisker-dependent texture discrimination task. Furthermore, the activity of parvalbumin-expressing inhibitory interneurons (PV+ INs) decreases in the stressed mouse due to reduced excitability of these neurons. Importantly, both behavioral defects and structural changes of L5 PNs are prevented by selective pharmacogenetic activation of PV+INs in the barrel cortex during stress. Finally, stressed mice raised under environmental enrichment (EE) maintain normal activation of PV+ INs, normal texture discrimination, and L5 PN spine dynamics similar to unstressed EE mice. Our findings suggest that the PV+ inhibitory circuit is crucial for normal synaptic dynamics in the mouse barrel cortex and sensory function. Pharmacological, pharmacogenetic and environmental approaches to prevent stress-induced maladaptive behaviors and synaptic malfunctions converge on the regulation of PV+ IN activity, pointing to a potential therapeutic target for stress-related disorders.

DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/ß-catenin signaling.

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/ß-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/ß-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/ß-catenin pathway.

Oxidative lipoprotein markers predict poor functional outcome in patients with minor stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: Oxidative stress plays an important role in acute ischaemic stroke. However, the association of oxidative lipoprotein markers, including oxidized low-density lipoprotein (oxLDL), oxLDL:high-density lipoprotein (HDL) and oxLDL:low-density lipoprotein (LDL), with functional outcome of minor stroke or transient ischaemic attack (TIA) remains unclear. We aimed to investigate the association between oxidative lipoprotein markers and poor functional outcome in patients with minor stroke or TIA. METHODS: All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE) trial. The poor functional outcome included modified Rankin Scale (mRS) score 2-6 and 3-6 at 90-day and 12-month follow-up. Multivariate logistic regression was used to investigate the associations of oxLDL, oxLDL:HDL and oxLDL:LDL with poor functional outcome. RESULTS: Among 3019 patients included in this study, the median (interquartile range) oxLDL, oxLDL:HDL and oxLDL:LDL were 13.96 (6.65-28.81), 4.52 (2.08-9.32) and 11.73 (5.27-24.85) µg/dL, respectively. After adjusted for confounding factors, patients in the highest oxLDL quartile had a higher proportion of mRS score 2-6 at 90 days [hazard ratio (HR), 1.78; 95% confidence interval (CI), 1.26-2.52] and 12 months (HR, 1.42; 95% CI, 1.01-1.99), and mRS score 3-6 at 90 days (HR, 1.98; 95% CI, 1.29-3.04) and 12 months (HR, 1.77; 95% CI, 1.09-2.89) when compared with the lowest oxLDL quartile (P < 0.05). Similar results were found for oxLDL:HDL and oxLDL:LDL. CONCLUSIONS: Higher levels of oxidative lipoprotein markers are independent predictors of poor functional outcome in patients with minor stroke or TIA at 90 days and 12 months.

A multicentre randomised controlled trial of the effect of intra-operative dexmedetomidine on cognitive decline after surgery.

Peri-operative dexmedetomidine can reduce rates of delirium immediately after surgery. We aimed to assess the effect of dexmedetomidine on cognition up to six postoperative months and its association with changes in serum concentrations of brain-derived neurotrophic factor on the third and seventh postoperative days. We randomly allocated 535 patients aged 65 years or more undergoing scheduled gastro-intestinal laparotomy to: intra-operative dexmedetomidine, 0.5 µg.kg-1 bolus followed by 0.4 µg.kg-1 .hr-1 infusion (n = 269), or placebo (n = 266). Dexmedetomidine reduced the rate of cognitive impairment: on the third postoperative day, 40/269 vs. 65/266, p = 0.006; on the seventh postoperative day, 31/269 vs. 49/266, p = 0.03 and at one postoperative month, 42/250 vs. 61/248, p = 0.04. Cognitive impairment at seven postoperative days was associated with changes in brain-derived neurotrophic factor concentrations on the third and seventh postoperative days; area under the receiver operating characteristic curve 0.63, p < 0.001 and 0.58, p = 0.016, respectively. Intra-operative dexmedetomidine reduced cognitive decline up to one postoperative month in elderly patients undergoing scheduled laparotomy, which was associated with changes in serum brain-derived neurotrophic factor.

[Utility of the type 3 portable monitor for the diagnosis of patients with obstructive sleep apnea].

Objective: To evaluate the utility of a portable monitor at home for diagnosis of obstructive sleep apnea (OSA) in Chinese adults. Methods: Eighty nine patients suspected of OSA underwent overnight, unattended home sleep apnea testing (HSAT) with a portable monitor (Nox-T3, Nox Medical Inc. Iceland)followed by an in-laboratory polysomnogram (PSG) with simultaneous portable monitor (PM) recording within one week. PSG and PM recorder were scored according to recommended guidelines by independent technicians. The correlation between PSG apnea hypopnea index (AHI) and PM respiratory disturbance index (RDI) were evaluated. Results: Sleep testing showed RDI was (30.0±20.9) events/h on HSAT, and (33.4±22.4) events/h on in-laboratory PM recording. Apnea-hypopnea index (AHI) on PSG was (35.1±23.7) events/h. There was significantly statistical difference among the three group (P<0.001). Both RDI on HSAT and RDI on in-laboratory PM correlated significantly with AHI on PSG (r=0.877, P<0.001 and r=0.962, P<0.001, respectively). Bland-Altman analysis of AHI on PSG versus RDI on HSAT showed a mean difference of 4.4 events/h; limits of agreement was -17.6 to 26.5 events/h. Closer agreements were present when comparing the simultaneous recordings, with AHI on PSG versus RDI on in-laboratory PM showing a mean difference of 1.4 events/h, and limits of agreement was -11.3 to 14.2 events/h. Based on a threshold of AHI≥5 events/h, RDI on HSAT had 98.8% sensitivity, 40.0% specificity. Using an AHI ≥ 15 events/h, RDI on HSAT had 91.5% sensitivity, 76.5% specificity. Conclusion: Type 3 PM has a good diagnostic value for adult OSA patients and there is close agreement between the Type 3 portable monitor and PSG.

TBX6 null variants and a common hypomorphic allele in congenital scoliosis.

BACKGROUND: Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. METHODS: We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multicenter series of 42 persons with 16p11.2 deletions. RESULTS: We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10(-6)). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. CONCLUSIONS: Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. (Funded by the National Basic Research Program of China and others.).

Knockout of a P-glycoprotein gene increases susceptibility to abamectin and emamectin benzoate in Spodoptera exigua.

P-glycoprotein [P-gp or the ATP-binding cassette transporter B1 (ABCB1)] is an important participant in multidrug resistance of cancer cells, yet the precise function of this arthropod transporter is unknown. The aim of this study was to determine the importance of P-gp for susceptibility to insecticides in the beet armyworm (Spodoptera exigua) using clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) gene-editing technology. We cloned an open reading frame (ORF) encoding the S. exigua P-gp protein (SeP-gp) predicted to display structural characteristics common to P-gp and other insect ABCB1 transporters. A knockout line with a frame shift deletion of four nucleotides in the SeP-gp ORF was established using the CRISPR/Cas9 gene-editing system to test its potential role in determining susceptibility to chemical insecticides or insecticidal proteins from the bacterium Bacillus thuringiensis (Bt). Results from comparative bioassays demonstrate that knockout of SeP-gp significantly increases susceptibility of S. exigua by around threefold to abamectin and emamectin benzoate (EB), but not to spinosad, chlorfenapyr, beta-cypermethrin, carbosulfan indoxacarb, chlorpyrifos, phoxim, diafenthiuron, chlorfluazuron, chlorantraniliprole or two Bt toxins (Cry1Ca and Cry1Fa). Our data support an important role for SeP-gp in susceptibility of S. exigua to abamectin and EB and imply that overexpression of SeP-gp may contribute to abamectin and EB resistance in S. exigua.