A General Framework for Identifying Hierarchical Interactions and Its Application to Genomics Data.

The analysis of hierarchical interactions has long been a challenging problem due to the large number of candidate main effects and interaction effects, and the need for accommodating the "main effects, interactions" hierarchy. The two-stage analysis methods enjoy simplicity and low computational cost, but contradict the fact that the outcome of interest is attributable to the joint effects of multiple main factors and their interactions. The existing joint analysis methods can accurately describe the underlying data generating process, but suffer from prohibitively high computational cost. And it is not straightforward to extend their optimization algorithms to general loss functions. To address this need, we develop a new computational method that is much faster than the existing joint analysis methods and rivals the runtimes of two-stage analysis. The proposed method, HierFabs, adopts the framework of the forward and backward stagewise algorithm and enjoys computational efficiency and broad applicability. To accommodate hierarchy without imposing additional constraints, it has newly developed forward and backward steps. It naturally accommodates the strong and weak hierarchy, and makes optimization much simpler and faster than in the existing studies. Optimality of HierFabs sequences is investigated theoretically. Simulations show that it outperforms the existing methods. The analysis of TCGA data on melanoma demonstrates its competitive practical performance.

Cloning of adipor1 and adipor2 genes in Rana dybowskii and its expression pattern upon infection / 生物工程学报

Adiponectin receptor 1 (AdipoR1) and Adiponectin receptor 2 (AdipoR2) can bind to adiponectin (AdipoQ) secreted by adipose tissue to participate in various physiological functions of the body. In order to explore the role of AdipoR1 and AdipoR2 in amphibians infected by Aeromonas hydrophila (Ah), the genes adipor1 and adipor2 of Rana dybowskii were cloned by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed by bioinformatics. The tissue expression difference of adipor1 and adipor2 was analyzed by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and an inflammatory model of R. dybowskii infected by Ah was constructed. The histopathological changes were observed by hematoxylin-eosin staining (HE staining); the expression profiles of adipor1 and adipor2 after infection were dynamically detected by qRT-PCR and Western blotting. The results show that AdipoR1 and AdipoR2 are cell membrane proteins with seven transmembrane domains. Phylogenetic tree also shows that AdipoR1 and AdipoR2 cluster with the amphibians in the same branch. qRT-PCR and Western blotting results show that adipor1 and adipor2 were up-regulated at different levels of transcription and translation upon Ah infection, but the response time and level were different. It is speculated that AdipoR1 and AdipoR2 participate in the process of bacterial immune response, providing a basis for further exploring the biological functions of AdipoR1 and AdipoR2 in amphibians.

A Wide-bandwidth Nanocomposite-Sensor Integrated Smart Mask for Tracking Multi-phase Respiratory Activities for COVID-19 Endemic

A global sentiment in early 2022 is that the COVID-19 virus could become endemic just like common cold flu viruses soon. The most optimistic view is that, with minimal precautions, such as vaccination, boosters and optional masking, life for most people will proceed as normal soon. However, as warned by A. Katzourakis of Oxford University recently [1], we must set aside lazy optimism, and must be realistic about the likely levels of death, disability and sickness that will be brought on by a COVID-19 endemic. Moreover, the world must also consider that continual circulation of the virus could give rise to new variants such as the new BA.2 variant (a subvariant of Omicron) continues to spread across the US and parts of Europe. Data from the CDC is already showing that BA.2 has been tripling in prevalence every two weeks [2]. Hence, globally, we must use available and proven weapons to continue to fight the COVID-19 viruses, i.e., effective vaccines, antiviral medications, diagnostic tests and stop an airborne virus transmission through social distancing, and mask wearing. For this work, we have demonstrated a smart mask with an optimally-coupled ultra-thin flexible soundwave sensors for tracking, classifying, and recognizing different respiratory activities, including breathing, speaking, and two-/tri-phase coughing; the masks functionality can also be augmented in the future to monitor other human physiological signals. Although researchers have integrated sensors into masks to detect respiratory activities in the past, they only based on measuring temperature and air flow during coughing, i.e., counting only the number of coughs. However, coughing is a process consisting of several phases, including an explosion of the air with glottal opening producing some noise-like waveform, a decrease of airflow to decrease sound amplitude, and a voiced stage which is the interruption of the air flow due to the closure of glottal and periodical vibration of partly glottis, which is not always present. Therefore, sensors used for cough detection should not be only sensitive to subtle air pressure but also the high-frequency vibrations, i.e., a pressure sensor that needs to be responsive to a wide input amplitude and bandwidth range, in order to detect air flows between hundreds of hertz from breath, and acoustic signals from voice that could reach [~] 8000 Hz. Respiratory activities data from thirty-one (31) human subjects were collected. Machine learning methods such as Support Vector Machines and Convolutional Neural Networks were used to classify the collected sensor data from the smart mask, which show an overall macro-recall of about 93.88% for the three respiratory sounds among all 31 subjects. For individual subjects, the 31 human subjects have the average macro-recall of 95.23% (ranging from 90% to 100%) for these 3 respiratory activities. Our work bridges the technological gap between ultra-lightweight but high-frequency response sensor material fabrication, signal transduction and conditioning, and applying machining learning algorithms to demonstrate a reliable wearable device for potential applications in continual healthy monitoring of subjects with cough symptoms during the eventual COVID-19 endemic. The monitoring and analysis of cough sound should be highly beneficial for human health management. These health monitoring data could then be shared with doctors via cloud storage and transmission technique to help disease diagnosis more effectively. Also, communication barriers caused by wearing masks can be alleviated by combining with the speech recognition techniques. In general, this research helps to advance the wearable device technology for tracking respiratory activities, similar to an Apple Watch or a Fitbit smartwatch in tracking physical and physiological activities.

Clinical, neuroimaging and gene mutation characteristics of McLeod syndrome and literature review / 中华神经科杂志

Objective:To study the characteristics of clinical, laboratory, imaging, genetic and differential diagnosis of McLeod syndrome.Methods:The clinical characteristics of 2 cases of McLeod syndrome confirmed by gene detection in Qilu Hospital (Qingdao) on June 27, 2018 and in Qilu Hospital of Shandong University on September 11, 2019 were analyzed retrospectively. And the characteristics of patients of McLeod syndrome reported in China were analyzed in combination with literature review.Results:Both of the 2 patients were adult male, aged 57 and 61 years, respectively, with a slowly progressive course, beginning with gradually involuntary movement of trunk and extremities, involving involuntary biting of the tongue and dysphagia. Two patients had mild cognitive impairment; one patient had emotional agitation. Imaging study showed atrophy of caput nuclei caudate. Neuroelectrophysiological examination of case 1 showed sensory axon neuropathy in both upper limbs with severe damage to the left ulnar nerve. Creatine kinase (CK) was mildly elevated in 2 patients. The peripheral blood smear of 1 patient showed increased acanthocytes, accounting for 13%, the other patient showed no increased acanthocyte. McLeod syndrome related gene was tested in the 2 patients, case 1 with deletion mutation of exon 2 of XK gene, and case 2 with hemizygotic mutation of XK gene c.898delC p.L300 *. Conclusions:The clinical manifestations of McLeod syndrome are various and the differential diagnosis is crucial. For elderly male with cephalic facial chorea, elevated CK level and neuromuscular diseases, the possibility of McLeod syndrome should be screened.

Bilateral basal ganglia hemorrhage due to tentorial dural arteriovenous fistula: a case report and systematic literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics of cerebral hemorrhage caused by tentorial dural arteriovenous fistula (TDAVF).Methods:An unusual TDAVF case admitted to the Department of Neurology, Qilu Hospital, Shandong University in March 2020, complicated with hypertension with successive bilateral basal ganglia hemorrhage in short term was reported. The characteristics of cerebral hemorrhage caused by TDAVF reported in the literature were summarized and analyzed.Results:Digital subtraction angiography (DSA) revealed that there was arteriovenous fistula in the tentorial foramen area of this patient (male, 33 years old), and the TDAVF was fed by the right meningohypophyseal trunk, bilateral middle meningeal artery and posterior cerebral artery. A shunted pouch was present in the tentorial foramen area, and retrograde reflux drainage was seen in the deep venous system, from the meningeal vein to superior sagittal sinus or sigmoid sinus. Transarterial embolization was performed and subsequently DSA showed obliteration of the fistula. This patient experienced no clinical decline or rehemorrhage during the 12 months follow-up period. Forty-one cases of TDAVF with hemorrhage of cerebral parenchyma which were reported before March 30, 2021 with detailed clinical and imaging data were summarized. The average age of onset of this group of patients was 57.2 years, and the ratio of male to female was about 3∶1. The hemorrhage was located in superior of the tentorium in 17 cases (41%), while in inferior of the tentorium in 24 cases (59%). Supratentorial intracerebral hemorrhage mainly occurred in occipital lobe and thalamus. DSA showed that the arteriovenous fistula was classified as Borden type Ⅲ or Cognard type Ⅳ in 36 cases (88%). Twenty-nine patients (71%) underwent a single surgical procedure, while 12 cases (29%) underwent combined surgical or other treatments. Overall, 37 patients (90%) achieved angiographically documented obliteration of the fistula and 39 patients (95%) experienced good or excellent outcomes.Conclusions:TDAVF often presents as cerebral parenchymal hemorrhage which is common in supratentorial region, but rare in basal ganglia region. The cause of cerebral hemorrhage in patients with hypertension may not be attributed to hypertension. Early diagnosis and intervention are of great significance to improve the prognosis of patients.

Clinical study of lupus nephritis complicated with renal thrombotic microangiopathy / 中华肾脏病杂志

Objective:To study the clinicopathological characteristics, treatment and prognosis in lupus nephritis (LN) patients with renal thrombotic microangiopathy (TMA), so as to provide more theoretical basis for clinicians to recognize and treat this disease.Methods:The clinical data of LN patients who underwent renal biopsy in the First Affiliated Hospital of Zhengzhou University from January 1, 2012 to May 31, 2019 were retrospectively collected and analyzed. According to renal clinicopathological examination, the patients were divided into renal TMA group and non-renal TMA group. The clinical data, laboratory examination, renal pathological examination, therapeutic measures and prognostic between the two groups were compared. Follow-up end points were defined as composite ends, including all-cause death, entry into end-stage renal disease, and estimated glomerular filtration rate decrease>50% of baseline. Kaplan-Meier survival curve and log-rank test were used to compare the difference of survival rate between the two groups, and multivariate Cox regression equation was used to analyze the risk factors of endpoint events in LN patients.Results:A total of 1 133 patients with LN were enrolled in this study. Patients with renal TMA were more likely to have hypertension ( χ2=16.310, P<0.001), higher baseline serum creatinine ( Z=-6.918, P<0.001) and 24-hour urine protein ( Z=-2.232, P=0.026), and higher renal pathology activity index (AI) score ( Z=1.957, P=0.001)and chronic index (CI) score ( Z=1.836, P=0.002). The proportions of hormone shock ( P<0.001) and plasma exchange ( P<0.001) in the renal TMA group were higher than those in non-renal TMA group. After treatment of (12±2) months, patients in the renal TMA group had a lower complete response rate ( χ2=10.455, P=0.001) and a higher non-response rate ( χ2=6.047, P=0.014) than those in non-renal TMA group, and were associated with worse prognosis (Log-rank test χ2=26.490, P<0.001). Renal TMA was an independent risk factor for poor prognosis ( HR=2.347, 95% CI 1.210-4.553, P=0.012). Conclusions:Compared with LN patients without renal TMA, LN patients with renal TMA are more likely to have hypertension, with higher serum creatinine, 24-hour urinary protein, AI and CI, suggesting poorer treatment response and renal prognosis. Moreover, renal TMA is an independent risk factor for poor prognosis in patients with LN.

Clinical characteristics of orobuccal involuntary movements induced by anticholinergic agents in patients with Parkinson′s disease and literature review / 中华神经科杂志

Objective:To study the clinical characteristics of orobuccal involuntary movements (OB) induced by anticholinergic agents.Methods:The clinical characteristics of patients with OB induced by anticholinergic agents in Qilu Hospital (Qingdao) from April 2018 to October 2021 and cases reported in the literature were analyzed in combination with literature review.Results:Seven patients in Qilu Hospital (Qingdao) and 10 cases in the literature were analyzed. Of these 7 patients, 6 were elderly female, with involuntary, repetitive, stereotypical movements of the lips, tongue, and sometimes of the jaw after intake of anticholinergic medication with the latency 21-60 days and the involuntary movements improved 7-30 days after discontinuation of anticholinergic medication. Of 10 cases reported in the literature, 7 were elderly female and 8 only with OB and 2 patients had extremities dyskinesia plus OB. Involuntary movements appeared after latency of 3-93 days following the introduction of anticholinergic drugs and resolved after latency of 2-60 days following their withdrawal.Conclusions:OB induced by anticholinergic agents mostly occur sub-acutely during the treatment of Parkinson′s disease, and can resolve in a short time after withdrawal, which is independent of the dose of levodopa and anticholinergic agents. The aging, female, and anxiety and depression may be the risk factors.

Cloning and tissue expression analysis of the LepROT gene of Rana dybowskii / 生物工程学报

Leptin receptor overlapping transcript (LepROT) plays multiple roles in the regulation of immune systems. However, very little information is available about the anti-infectious mechanisms of amphibians LepROT. In this study, the cDNA sequence of the Rana dybowskii LepROT gene was determined by using RT-PCR and bioinformatics analysis. Then, the Aeromonas hydrophila (Ah) and lipopolysaccharides (LPS) infected models of R. dybowskii was constructed to obtain histopathological characteristics. Constitutive expression of LepROT mRNA and NF-κB signaling pathway were detected by real-time quantitative PCR. The full-length cDNA of LepROT gene was 396 bp and encoded 131 amino acids. Amino acid sequence analysis revealed LepROT shares 93.74% and 86.39% identity with homologues from other amphibians and mammals respectively, and the LepROT gene was quite conserved among different species. After infection, the relative expression levels of LepROT, NF-κB, IKKα and IKKβ mRNA were all significantly upregulated (P < 0.01), but showed a diverse temporal pattern of up-regulation in different tissues. Therefore, it was proposed that the LepROT gene of R. dybowskii might activate the NF-κB signaling pathway to exert anti-infectious effects, thus providing evidence for further extending the biological function of LepROT.

Analysis of clinical, imaging and endoscopic characteristics of 14 patients with idiopathic mesenteric phlebosclerosis / 中华消化杂志

Objective:To investigate the clinical, imaging and endoscopic characteristics of idiopathic mesenteric phlebosclerosis (IMP).Methods:From January 2010 to December 2020, 14 patients with IMP diagnosed and treated at the Quzhou Hospital Affiliated to Wenzhou Medical University (Quzhou People′s Hospital) were enrolled. All patients underwent abdominal X-ray, contrast enhanced computed tomography (CT) and endoscopy. Three cases accepted double-contrast barium enema and 11 cases underwent endoscopic biopsy. Three of the 14 IMP patients underwent surgery and pathological examination because of intestinal perforation or intestinal obstruction that failed conservative treatment. The general data (such as gender, drinking history, etc.), clinical symptoms, complications, imaging (abdominal X-ray, CT, double-contrast barium enema) and endoscopic features were retrospectively analyzed. Descriptive method was used for statistical analysis.Results:Among the 14 IMP patients, 13 cases were male and one case was female. All the 13 male cases had long history of drinking Chinese herbal medicine wine, among them, 8 patients consumed acanthopanax bark wine. Complications occurred in 7 cases, including 5 cases of intestinal obstruction and 2 cases of intestinal perforation. The clinical symptoms of 14 IMP patients were nonspecific, mostly manifested as abdominal pain (11 cases), abdominal distension (6 cases), diarrhea (6 cases), nausea and vomiting (4 cases), and constipation (2 cases). Abdominal X-ray images mainly showed multiple irregular calcifications along involved colon. The images of 3 patients received double-contrast barium enema demonstrated shallowness or disappearance of semilunar folds, rigid colonic wall, narrowed lumen and " thumb printing". The typical CT images indicated edema and thickening of the involved intestinal wall, blurred mesenteric fat space, spot, thread-like, and curved calcification of mesenteric vein and colonic wall. Typical endoscopic findings included dark-purple colored mucosa, congestion, edema, erosion and ulceration, and focal nodular surface and visible varicose veins.Conclusions:IMP has typical imaging and endoscopic characteristics, and the combination of them can diagnose and evaluate IMP more accurately.

Effects of electroacupuncture at Zusanli on duodenal Caspase-1 and GSDMD of rats with functional dyspepsia / 中华物理医学与康复杂志

Objective:To explore any effect of electroacupuncture (EA) at the Zusanli point on the scorch death of duodenal cells in rats with functional dyspepsia (FD) and possible mechanisms.Methods:Twenty-four 7-day-old Sprague-Dawley rats were randomly divided into a blank group, a model group and an EA group, each of 8. FD was induced in both the model and EA group rats using iodoacetamide gavage with tail-clip stimulation. After successful modeling the EA group was given acupuncture at the Zusanli point and then connected with a Korean acupuncture point nerve stimulator for 2 weeks. The other 2 groups were not given any intervention. The rats′ body weight was recorded before and after the modeling, as well as 7 and 14 days later. The gastric emptying rate and the small intestine propulsion rate of the three groups were detected right after the EA intervention, and the serum expression levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6) were measured using enzyme-linked immunoassays. Real-time fluorescence quantitative polymerase chain reactions were used to detect the transcription levels of IL-1β and IL-6 in the rats′ duodenums, while western blotting was employed to assess the expression of caspase-1 P20 and dermatin D (GSDMD) in their duodenums.Results:After successful modeling, the average body weight of the rats in the model and EA groups was significantly different from that in blank group, and after 7 and 14 days the average body weight of the former groups was significantly different from that of the blank group, with significant differences between the two groups as well. After the EA intervention significant differences were observed in gastric reside and small intestine propulsion rate between the EA group and the model group, as well as between the model and the blank group. After the intervention, there were significant differences between the blank group and the other two groups in the average expression of IL-1β and IL-6 in serum, IL-1β and IL-6 mRNA in the duodenum, as well as the GSDMD and caspase-1 p20 proteins in the duodenum. There were significant differences between the model and EA groups in all of the above measurements.Conclusions:EA at the Zusanli point can significantly reduce the level of scorch death in the duodenum of FD rats, as well as relieve low-grade duodenal inflammation and the clinical symptoms of FD. Its mechanism may be related to the down-regulation of the expression of caspase-1 P20 and GSDMD-N protein, and of inflammatory factors such as IL-1β and IL-6, relieving low-grade duodenal inflammation.

Projecting the impact of SARS-CoV-2 variants on the COVID-19 epidemic and social restoration in the United States: a mathematical modelling study

BackgroundThe SARS-CoV-2 Alpha variant B.1.1.7 became prevalent in the United States (US). We aimed to evaluate the impact of vaccination scale-up and potential reduction in the vaccination effectiveness on the COVID-19 epidemic and social restoration in the US. MethodsWe extended a published compartmental model and calibrated the model to the latest US COVID-19 data. We estimated the vaccine effectiveness against B.1.1.7 and evaluated the impact of a potential reduction in vaccine effectiveness on future epidemics. We projected the epidemic trends under different levels of social restoration. ResultsWe estimated the overall existing vaccine effectiveness against B.1.1.7 to be 88.5% (95%CI: 87.4-89.5%) and vaccination coverage would reach 70% by the end of August, 2021. With this vaccine effectiveness and coverage, we anticipated 498,972 (109,998-885,947) cumulative infections and 15,443 (3,828-27,057) deaths nationwide over the next 12 months, of which 95.0% infections and 93.3% deaths were caused by B.1.1.7. Complete social restoration at 70% vaccination coverage would only slightly increase cumulative infections and deaths to 511,159 (110,578-911,740) and 15,739 (3,841-27,638), respectively. However, if the vaccine effectiveness were reduced to 75%, 50% or 25% due to new SARS-CoV-2 variants, we predicted 667,075 (130,682-1,203,468), 1.7m (0.2-3.2m), 19.0m (5.3-32.7m) new infections and 19,249 (4,281-34,217), 42,265 (5,081-79,448), 426,860 (117,229-736,490) cumulative deaths to occur over the next 12 months. Further, social restoration at a lower vaccination coverage would lead to even greater future outbreaks. ConclusionCurrent COVID-19 vaccines remain effective against the B.1.1.7 variant, and 70% vaccination coverage would be sufficient to restore social activities to a pre-pandemic level. Further reduction in vaccine effectiveness against SARS-CoV-2 variants would result in a potential surge of the epidemic in the future.

Effects of Mangiferin on Glucose and Lipid Metabolism of Insulin-resistant HepG2 Cells / 中国药房

OBJECTIVE：To analyze the effects of mangiferin （MGF）on glucose and lipid metabolism in insulin resistance （IR）HepG2 cells，and to explore the potential mechanism. METHODS ：Using human hepatoma HepG 2 cells as research objects ， 1 mmol/L palmitic acid and 2 mmol/L oleic acid were used to establish the IR-HepG 2 cell model. Using metformin hydrochloride as positive control ，the effects of low-concentration ，medium-concentration and high-concentration MGF （125，250，500 μmol/L）on the corrected glucose consumption ，the contents of triglyceride （TG）and total cholesterol （TC）in IR-HepG 2 cells were detected. The mRNA expression of APN ，AdipoR2，APPL1，AMPK in the upstream of AMPK signaling pathway and IRS- 1，Akt and GLUT4 in the downstream insulin signaling pathway were detected by RT-PCR. The phosphorylation level of AMPK protein was detected by Western blot assay. RESULTS ：Compared with control group ，corrected glucose consumption ，mRNA expression of APN，AdipoR2，APPL1，AMPK，IRS-1 and GLUT 4，as well as the phosphorylation level of AMPK protein were decreased significantly in model group ，while the contents of TG and TC were increased significantly （P＜0.05 or P＜0.01）. Compared with model group ， corrected glucose consumption ， mRNA expression of APN （except for MGF medium-concentration and high-concentration groups ），AdipoR2，APPL1，AMPK（except for MGF medium-concentration and high-concentration groups ）， IRS-1（except for MGF medium-concentration and high-concentration groups ），Akt（except for positive control group ），GLUT4 （except for MGF high-concentration group ）were increased significantly in administration groups ，while the contents of TG and TC were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：Mangiferin may activate APN ，which is the upstream target of pathway ，and then regulate AMPK signaling pathway ，so as to promote glucose uptake of IR-HepG 2 cells，reduce TG and TC contents，and improve IR and abnormal glucose and lipid metabolism.

Polychlorinated biphenyls in a grassland food network: Concentrations, biomagnification, and transmission of toxicity.

The production of polychlorinated biphenyls (PCBs) is prohibited by the Stockholm Convention in 2001, but the unintentionally produced PCBs are still continuously discharged into the environment. In this study, the distributions, biomagnification and toxicity amplification in a grassland food network (including inorganic environment, animals and vegetation) were investigated. PCB concentrations in various samples were determined, and PCBs appeared to be enriched as the trophic level increased. The PCB concentrations in the inorganic environment samples ranged from below the detection limit to 0.329 ng g-1, and the PCB concentrations in vegetation were 0.0829-4.45 ng g-1. The PCB concentration in snake subcutaneous fat (8.74 ng g-1 lipid weight) was higher than the concentrations in other animal samples, and the next highest concentration was found in yellow weasel muscle (7.31 ng g-1 lipid weight). Biomagnification factors were calculated for different PCBs and different organisms. Biomagnification was most obvious for organisms at the top of the food chain (the snake/mouse biomagnification ratio was >1000). The PCB-126 toxic equivalent concentration increased markedly as the trophic level increased. The toxic equivalent concentrations were 1200 times higher for high trophic level biota than low trophic level biota. PCB-169 had the highest toxic equivalent concentrations for the animal hair samples (0.00001 pg toxic equivalents g-1). However, PCB-81 had the highest toxicity equivalent concentrations for the herdsmen hair samples. PCBs found at relatively low concentrations and low toxic equivalent concentrations at low trophic levels can be biomagnified as they are transferred through the food chain and can reach high actual and toxic equivalent concentrations at high trophic levels.

Correlations of Methylenetetrahydrofolate Reductase Gene Polymorphism and Genomic DNA Hypomethylation Level with Ankylosing Spondylitis / 中国医学科学院学报

To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% 5.0%;=9.874, =0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)μmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)μmol/L](=24.402, <0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)μmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)μmol/L](=12.088, =0.01)and the C/T genotype [(17.80±2.18)μmol/L](=6.496, =0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(=5.655, <0.001)and also significantly lower than those of the C/C genotype(=11.514, <0.001)and the C/T genotype in AS group(=10.287, <0.001). In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.

Advances in research on the relationship between diabetes and Parkinson's disease / 中华神经科杂志

Parkinson's disease is one of the most common neurodegenerative diseases,characterized by progressive degeneration of dopaminergic neurons.Diabetes is one of its common comorbidities,because both are affected by genetic factors and various environmental factors,as well as remarkably similar dysregulated pathways.The relationship between the two is receiving more and more attention.In particular,application of hypoglycemic drugs in Parkinson's disease has become a research hotspot in recent years.This article reviews the clinical features of Parkinson's disease and diabetes,the clinical features of Parkinson's disease with diabetes,and the application of hypoglycemic agents in Parkinson's disease.

Pulmonary nodule detection method based on convolutional neural network / 生物医学工程学杂志

A method was proposed to detect pulmonary nodules in low-dose computed tomography (CT) images by two-dimensional convolutional neural network under the condition of fine image preprocessing. Firstly, CT image preprocessing was carried out by image clipping, normalization and other algorithms. Then the positive samples were expanded to balance the number of positive and negative samples in convolutional neural network. Finally, the model with the best performance was obtained by training two-dimensional convolutional neural network and constantly optimizing network parameters. The model was evaluated in Lung Nodule Analysis 2016(LUNA16) dataset by means of five-fold cross validation, and each group's average model experiment results were obtained with the final accuracy of 92.3%, sensitivity of 92.1% and specificity of 92.6%.Compared with other existing automatic detection and classification methods for pulmonary nodules, all indexes were improved. Subsequently, the model perturbation experiment was carried out on this basis. The experimental results showed that the model is stable and has certain anti-interference ability, which could effectively identify pulmonary nodules and provide auxiliary diagnostic advice for early screening of lung cancer.

Characteristics of clinical manifestations and molecular genetics of late-onset cobalamin C deficiency / 中华神经科杂志

Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.

Sleep benefit and its correlation factors in Parkinson's disease / 中华神经科杂志

Objective To analyze the phenomenon of sleep benefit in Parkinson's disease (PD)and its correlation factors.Methods One hundred PD patients in Department of Neurology,Qilu Hospital of Shandong University from February 2017 to November 2017 were included.They were recorded in detail the clinical information and clinical classification.Sleep conditions were assessed by Pittsburgh Sleep Quality Index,Parkinson Disease Sleep Scale,Epworth Sleepiness Disorder Scale and Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire.The general information,disease duration,medication,movement function,sleep condition and anxiety status were compared between sleep benefit group and without sleep benefit group.The correlation factors of sleep benefit was evaluated using unconditional Logistic regression analysis.Results Fifty-one cases (51％) of sleep benefit were determined in our cohort of 100 PD patients.Sleep benefit group adminstered lower levodopa equivalent daily dose (LEDD,(354.77 ± 279.64) mg/d) compared with patients without sleep benefit ((510.76 ± 266.26) mg/d,t =-2.734,P =0.006),including levodopa ((289.04 ± 228.73) mg/d vs (392.65 ± 211.20) mg/d,t =-2.366,P =0.021) and dopamine agonist dose ((41.13 ± 51.48) mg/d vs (68.01 ± 57.10) mg/d,t =-1.950,P =0.054).Sleep benefit group had higher percentage of using dopamine agonist (23(45.1％) vs 35 (71.4％),x2 =7.112,P=0.008) and longer duration of nocturnal sleep episode ((6.51 ± 1.31) h vs (5.89 ± 1.29) h,t =2.412,P =0.018).In addition,sleep benefit had a higher prevalence in tremor-dominant subtype of PD (19/27 (70.4％) vs 20/46 (43.5％),x2 =4.855,P =0.025).Logistic regression indicated that sleep benefit had a positive correlation with duration of nocturnal sleep episode and tremor-dominant subtype,as well as a negative correlation with LEDD and dose of levodopa.LEDD and duration of nocturnal sleep episode were the independent factors of sleep benefit (OR =0.998,95％CI 0.997-1.000,P＜0.05;OR=1.407,95％CI1.004-1.972,P＜0.05).Conclusion PD patients with sleep benefit administered low dose of dopamine and took long nocturnal sleep,which may relate to the relativelv preserved dopamine storage function of dopaminergic neurons.

Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis / 中南大学学报(医学版)

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Effects of Extracts from Different Polar Parts of Li Medicine Alpinia oxyphylla Fruit on Model Mice with Experimental Colitis / 中国药房

OBJECTIVE:To investigate the effects of 4 polar parts extracts from Li medicine Alpinia oxyphylla fruit on model mice with experimental colitis,and screen the effective parts of A. oxyphylla fruit in the treatment of colitis. METHODS:After 70% ethanol extract dispersed by water,petroleum ether,trichloromethane,ethyl acetate and n-butanol were used in turn to obtain extractions in related parts. 42 mice were randomly divided into modeling group(36 mice)and blank group(6 mice). Mice in mod-eling group were taken 2,4,6-nitrobenzne sulfonic acid method to replicate the experiment colitis. After modeling,model mice were randomly divided into model group,positive group(Sulfasalazine enteric coated tablets,52 g/kg),petroleum ether,trichloro-methane,ethyl acetate,n-butanol extract from A. oxyphylla fruit groups(10 g/kg,calculated by crude drug),6 in each group,in-tragastrically administrated once a day,for 9 d,0.2 mL/10 g;mice in blank group and model group were intragastrically given nor-mal saline. After administration,body mass of mice was determined,disease activity index(DAI)was scored and colonic myelo-peroxidase(MPO),superoxide dismutase(SOD),malondialdehyde(MDA)activities in colon tissue were detected,and the colon pathological changes were observed and scored. RESULTS:Compared with blank group,decrease percentage of body mass,DAI score,MPO and MDA activities in colon tissue in model group were increased(P<0.05 or P<0.01);colon tissue was pathologi-cally changed. Compared with model group,body mass was increased,DAI score,MPO activity and pathological score in each ad-ministration groups were decreased;SOD activities in positive group,n-butanol extract from A. oxyphylla fruit group and ethyl ace-tate extract from A. oxyphylla fruit group were significantly increased,MDA activities in positive group and ethyl acetate extract from A. oxyphylla fruit group were significantly decreased,with statistical significances (P<0.05 or P<0.01). CONCLUSIONS:The 4 polar parts extracs from A. oxyphylla fruit have certain improvement effects on model mice with experimental colitis, in which ethyl acetate and n-butanol parts are preferred.