Histogram analysis of diffusion kurtosis imaging of deep brain nuclei in Parkinson's disease with different motor subtypes.

AIM: To evaluate the diagnostic and differential efficacy of diffusion kurtosis imaging (DKI) histogram analysis for different motor subtypes of Parkinson's disease (PD). MATERIALS AND METHODS: Seventy PD patients including 40 with postural instability and gait disorder (PIGD) and 30 with tremor-dominant (TD) and 36 healthy controls (HC) were enrolled prospectively and underwent MRI examinations. The regions of interest (ROI) in the deep brain nuclei were delineated and features were extracted on the map of mean kurtosis (MK), axial kurtosis (Ka), and radial kurtosis (Kr), respectively. The differences in histogram features between PD patients and HC and between patients with PIGD and TD were compared. The areas under the curve (AUCs) were calculated to evaluate the diagnostic efficacy of all histogram features. The correlations between histogram features and clinical indicators were evaluated. RESULTS: Some DKI histogram features were significantly different between PD patients and HC, and also different between patients with PIGD and TD (all p<0.05). MK of the substantia nigra pars reticulate (SNprkurtosis), Ka of the substantia nigra pars compacta (SNpc) 50 percentile (SNpcP50), and Kr of SNpc 90th percentile showed the highest AUC for distinguishing patients with PIGD from HC. MK-SNpc 10th percentile, Ka-SNpc 25th percentile, and Kr of the head of the caudate nucleus (CN) 90th percentile had the highest AUC for distinguishing patients with TD from HC. MK of the putamen 10th percentile combined with Ka of the bilateral red nucleus RNkurtosis yielded the highest diagnostic performance with an AUC of 0.762 for distinguishing patients with PIGD from TD. Certain DKI histogram features were correlated with Hoehn-Yahr (H&Y) stage, Mini Mental State Examination (MMSE) score, tremor score, and PIGD score (all p<0.05). CONCLUSION: DKI histogram analysis was useful to diagnose and discriminate different motor subtypes of PD. Certain DKI histogram features correlated with clinical indicators.

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

[Research advances in post-tuberculosis lung disease].

The burden of tuberculosis remains high in China. Although successfully cured of tuberculosis, a large proportion of patients still suffer from post-tuberculosis lung disease (PTLD), causing great harm to individuals and societies. PTLD is a group of heterogeneous disorders that affects airways, lung parenchyma, pleura, and/or pulmonary vasculature. The related etiology and pathogenesis remain unclear, and are likely the result of the interplay between the host immune responses, pathogens, and environmental factors. Advances in prevention and treatment mainly involve adjuvant therapy and pulmonary rehabilitation. Since PTLD patients mostly visit respiratory departments for consultation, it is essential for respiratory physicians to improve the awareness PTLD, and therefore the research progress of PTLD is reviewed.

[Interpretations of guideline for the management of diabetes mellitus in the elderly in China (2021 edition)].

Elderly diabetic patients in China accounts for one fourth of the total number of elderly diabetic patients in the world, ranking the first worldwide. In 2021, National Center of Gerontology, Chinese Society of Geriatrics and Diabetes Professional Committee of Chinese Aging Well Association issued China's first guideline on elderly diabetic patients--Guideline for the management of diabetes mellitus in the elderly in China (2021 edition). The present article interprets parts of the important recommendations of the guideline, aiming to facilitate its implementation in clinical practice effectively and improve the clinical prognosis of elderly diabetic patients in our country.

[The preventive effect of four drugs on acute mountain sickness: a Bayesian network meta-analysis].

Objective: To compare and predict the preventive effects of acetazolamide and other drugs on acute mountain sickness(AMS). Methods: Following the retrieval strategy of PRISMA statement of systematic review and meta-analysis, we searched the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, etc. from January 1, 1980 to November 30, 2020, and randomized controlled trials (RCT) consistent with drug prevention of AMS were conducted. Using R and other statistical software, Markov chain-Monte Carlo method was carried out for network meta-analysis under Bayesian framework, and node separation method was performed to check the consistency of closed-loop research. Results: Twenty-three literatures (25 studies) were included to compare the preventive effects of 4 drugs on AMS. Bayesian network meta-analysis showed that the incidence of AMS in acetazolamide group (ACE), dexamethasone group (DEX), ginkgo biloba extract group (GBE) and rhodiola group (RHO) was lower than that in placebo group (PLA). In the comparison of drug groups, the incidence of AMS in ACE, DEX and RHO was lower than that in GBE. There was no statistically significant difference in the incidence of AMS among ACE, DEX and RHO groups. Eight of these studies reported the effects of two drugs on pulse oxygen saturation (SpO2) in people entering the target altitude. Bayesian network meta-analysis showed that SpO2 in RHO was higher than that in ACE and PLA, but there was no statistically significant difference in SpO2 between ACE and PLA. The probability ranking of prevention AMS effect grade showed that the rank 5th probability of AMS in ACE, DEX, GBE, RHO and PLA was 45.72%, 48.80%, 0, 5.48% and 0, respectively. The probability ranking of improving the SpO2 level of the target altitude population showed that the probability of the ACE, RHO and PLA ranking 1st in improving the SpO2 effect at the target altitude was 2.27%, 97.66% and 0.07%, respectively; the results of direct comparison were in good agreement with those of Bayesian prediction model indirectly, and there was no statistical difference. Conclusions: Acetazolamide and dexamethasone can effectively prevent AMS, and should be the first choice for related supplementary research in the future. Rhodiola not only improves the SpO2 of people entering high altitude, but also reduces the incidence of AMS, which needs more attention. Ginkgo biloba extract is not as effective as the above three drugs in preventing AMS and should be used depending on clinical situations.

Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14.

AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.

Genome-wide association study reveals novel loci associated with fat-deposition and meat-quality traits in Pekin ducks.

Meat-quality traits play an essential role in meat poultry production. To determine the genetic mechanisms of meat quality in Pekin ducks, we performed a large-scale GWAS to identify quantitative trait loci affecting meat quality in Pekin ducks. We measured 10 traits in 542 Pekin ducks and genotyped each duck using genotyping-by-sequencing. The genetic parameters (genomic heritability, genetic correlation) for 10 meat-quality related traits were evaluated. Based on the large genotype-phenotype dataset, we performed GWASs for all of these traits. A total of 33 significant QTL (P < 3.03 × 10-5 ) across 13 chromosomes were identified by loci-based analysis. Some newly identified candidate genes were discovered for fat-deposition and meat-quality traits, including PAG1 for body weight and eviscerated weight, INTU and NUP35 for abdominal fat weight and ratio, NUP3 and ARHGDIB for skin fat weight and ratio, GOLGA5 for breast muscle toughness and breast tenderness, and CTDSPL and PKP1 for breast muscle thickness. The current study is the first systematic report regarding duck meat quality.

MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1, IGF1R and BCL2.

OBJECTIVE: This study aimed to explore potential microRNAs (miRNAs), which participate in the pathological process of condylar hyperplasia (CH) through targeting specific proliferation- and apoptosis- related genes of chondrocytes. METHODS: Insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B-cell CLL/lymphoma 2 (BCL2) in CH cartilage were detected by real-time polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence. MiRanda and TargetScanS algorithms were used to predict certain miRNAs in CH chondrocytes concurrently modulating the above three genes. MiR-15b was screened and identified using real-time PCR. After transfection of miR-15b mimics or inhibitor into CH chondrocytes, expression of the above three genes was detected by real-time PCR and western blot, meanwhile, cell proliferation and apoptosis was examined by CCK8, cell cycle assays, flow cytometry and Hoechst staining. Dual luciferase activity was performed to identify the direct regulation of miR-15b on IGF1, IGF1R and BCL2. RESULTS: Expression of IGF1, IGF1R and BCL2 increased in CH cartilage. Seven microRNAs concurrently correlated with IGF1, IGF1R and BCL2. Among them, only miR-15b significantly changed in CH chondrocytes. Overexpression of miR-15b in CH chondrocytes suppressed the expression of IGF1, IGF1R and BCL2, while it increased when miR-15b was knockdown. Furthermore, miR-15b suppressed their expression by directly binding to its 3'-UTR in these cells. Besides, miR-15b hampered chondrocytes proliferation through targeting IGF1 and IGF1R and accelerated chondrocytes apoptosis through targeting BCL2. CONCLUSION: Suppressed miR-15b contributed to enhanced proliferation capacity and weakened apoptosis of chondrocytes through augmentation of IGF1, IGF1R and BCL2, thereby resulting in development of CH.

Elderly males with or without existing osteoporotic vertebral fracture have much lower future vertebral fracture risk than elderly females: the MrOS (Hong Kong) year-4 follow-up spine radiograph study.

MrOS (Hong Kong)'s year-4 follow-up shows, for subjects at baseline without vertebral deformity (VD) and endplate or/and cortex fracture (ECF), the VD progression/new VD rate during follow-up in males was half of our paired MsOS (Hong Kong) study's results. For those with VD or ECF, the VD progression/new VD was less than one sixth of females' rate. INTRODUCTION: This study documents MrOS (Hong Kong)'s year-4 follow-up, and the results are compared with the MsOS (Hong Kong) study. Of elderly females with Genant's grade-0, -1, -2, and -3 VD, at year-4 follow-up, 4.6%, 8%, 10.6%, and 28.9% had at least one VD progression or incident VD, respectively. METHODS: Spine radiographs of 1500 Chinese males with baseline (mean age 71.7 years, range 65-91 years) and year-4 follow-up were evaluated according to Genant's VD criteria and ECF (non-existent, ECF0; or existent, ECF1). Grade-2 VDs were divided into mild (VD2m, 25-34% height loss) and severe (VD2s, 34-40% height loss) subgroups. Study subjects were graded into eight categories: VD0/ECF0, VD1/ECF0, VD2m/ECF0, VD0/ECF1, VD1/ECF1, VD2m/ECF1, VD2s/ECF1, and VD3/ECF1. With an existing VD, a further height loss of ≥ 15% was a VD progression. A new VD incident was a change from grade-0 to grade-2/3, or to grade-1 with ≥ 10% height loss. RESULTS: Of subjects with Genant's grade-0, 2.05% (25/1219) developed at least one VD progression or/and new VD, while of subjects with Genant's grade-1, -2, and -3 VD, only 2% (3/149), 3.1% (3/96), and 2.8% (1/36) developed at least one VD progression/new VD, respectively. Among the three ECF0 groups, there was a significant difference in new ECF incidence, with VD0/ECF0 being the lowest and VD2m/ECF0 being the highest. CONCLUSION: VD progression/new VD is much less common in elderly men than in elderly women. Vertebrae with VD had a higher risk of developing ECF.

Osteoporotic vertebral deformity with endplate/cortex fracture is associated with higher further vertebral fracture risk: the Ms. OS (Hong Kong) study results.

Compared with vertebrae without deformity, vertebrae with mild/moderate deformity have a higher risk of endplate or/and cortex fracture (ecf). Compared with subjects without ecf, subjects with ecf are at a higher risk of short-term (4-year period) deformity progression and new incident deformity. INTRODUCTION: The progression and incidence of osteoporotic vertebral deformity/fracture (VD/VF) in elderly Chinese females remain not well documented. METHODS: Spine radiographs of 1533 Chinese females with baseline and year-4 follow-up (mean age 75.7 years) were evaluated according to Genant's VD criteria and endplate/cortex fracture (non-existent: ecf0 or existent: ecf1). Grade-2 VDs were divided into mild (vd2m, 25-34% height loss) and severe (vd2s, 34-40% height loss) subgroups. According to their VD/VF, subjects were graded into seven categories: vd0/ecf0, vd1/ecf0, vd2m/ecf0, vd1/ecf1, vd2m/ecf1, vd2s/ecf1, and vd3/ecf1. With an existing VD, a further height loss of ≥ 15% was a VD progression. A new incident VD was a change from grade-0 to grade-2/3 or to grade-1 with ≥ 10% height loss. RESULTS: Of subjects with Genant's grades 0, - 1, - 2, and - 3 VD, at follow-up, 4.6%, 8%, 10.6%, and 28.9% had at least one VD progression or new incident VD respectively. Among the three ecf0 groups, there was no difference in VD progression or new VD; while there was a significant difference in new ecf incidence, with vd0/ecf0 being lowest and vd2m/ecf0 being highest. Vd1/ecf0 and vd2m/ecf0 vertebrae had a higher risk of turning to ecf1 than vd0/ecf0 vertebrae. If vd1/ecf0 and vd2m/ecf0 subjects were combined together (range 20-34% height loss) to compare with vd1/ecf1 and vd2m/ecf1 subjects, the latter had significantly higher VD progression and new VD rates. CONCLUSION: Vertebrae with grade-1/2 VDs had a higher risk of developing ECF. Subjects with pre-existing ECFs had a higher risk of worsening or new vertebral deformities.

Effective g Factor of Subgap States in Hybrid Nanowires.

We use the effective g factor of Andreev subgap states in an axial magnetic field to investigate how the superconducting density of states is distributed between the semiconductor core and the superconducting shell in hybrid nanowires. We find a steplike reduction of the Andreev g factor and an improved hard gap with reduced carrier density in the nanowire, controlled by gate voltage. These observations are relevant for Majorana devices, which require tunable carrier density and a g factor exceeding that of the parent superconductor.

Selective-Area-Grown Semiconductor-Superconductor Hybrids: A Basis for Topological Networks.

We introduce selective area grown hybrid InAs/Al nanowires based on molecular beam epitaxy, allowing arbitrary semiconductor-superconductor networks containing loops and branches. Transport reveals a hard induced gap and unpoisoned 2e-periodic Coulomb blockade, with temperature dependent 1e features in agreement with theory. Coulomb peak spacing in parallel magnetic field displays overshoot, indicating an oscillating discrete near-zero subgap state consistent with device length. Finally, we investigate a loop network, finding strong spin-orbit coupling and a coherence length of several microns. These results demonstrate the potential of this platform for scalable topological networks among other applications.

Screening for general anxiety disorders in postmenopausal women with symptomatic pelvic organ prolapse.

OBJECTIVE: This study aimed to investigate the prevalence of general anxiety disorder (GAD) among postmenopausal women with symptomatic pelvic organ prolapse (POP) and to identify its associated factors. METHODS: A cross-sectional study was conducted among postmenopausal women with symptomatic POP. Sociodemographic data and medical histories were obtained. Participants completed the POP Quantification (POP-Q), the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and the Pelvic Floor Distress Inventory (PFDI-20) measures. Measures of GAD were obtained using the Generalized Anxiety Disorder-7 (GAD-7). The data were analyzed using independent sample t-tests, the Mann-Whitney U-test, χ2 tests, Fisher's exact tests and logistic regression. RESULTS: Of the 177 participants interviewed, 19.2% had symptoms of GAD. There were no statistically significant differences in the sociodemographic characteristics or the POP-Q stage between women with and without GAD (p > 0.05). GAD was significantly associated with higher PFDI-20 and PFIQ-7 subscale scores (p < 0.05). After multiple logistic regression analyses, only the PFIQ-7 subscale UIQ-7 (odds ratio = 1.025, 95% confidence interval 1.007-1.043, p = 0.005) and the PFDI-20 subscale CRADI-8 (odds ratio = 1.025, 95% confidence interval 1.004-1.047, p = 0.021), which represented the impact on quality of life from lower urinary tract symptoms and the distress caused by bowel dysfunction, were risk factors that were independently associated with GAD. CONCLUSIONS: GAD is prevalent in almost one-fifth of postmenopausal women with symptomatic POP. GAD is not associated with the severity of the POP-Q stage but is associated with higher scores for lower urinary tract and bowel dysfunction caused by POP.

Experimental demonstrations of 30Gb/s/λ digital orthogonal filtering-multiplexed multiple channel transmissions over IMDD PON systems utilizing 10G-class optical devices.

By utilizing digital orthogonal filtering (DOF) in the digital domain, we report, for the first time, experimental demonstrations of aggregated 30.078Gb/s/λ transmissions of DOF-multiplexed spectrally-overlapped and/or frequency gapless six channels over IMDD PON systems incorporating off-the-shelf and low-cost 10G-class optical devices. Experimental results show that simple adaptive channel power loading implemented in the digital domain enables very similar transmission performances of individual channels regardless of their locations in the digital filter space. As a direct result of the interplay between the transmission system-associated negative chromatic dispersion and the intensity modulation-induced frequency chirp, negative power penalties of >0.2dB are experimentally observed for all the involved channels under various transmission system configurations. In addition, excellent performance robustness of the demonstrated systems is also obtainable for various transmission distances up to 45km.

MiR-200c inhibits metastasis of breast tumor via the downregulation of Foxf2.

The forkhead box F2 (Foxf2) gene suppresses epithelial-mesenchymal transition via the modulation of transcription of zinc finger E-box-binding homeobox 1 (Zeb1) and epithelial (E)-cadherin, thereby inhibiting tumor metastasis. Additionally, the specific binding of microRNA (miR)-200c to Foxf2 mRNA impedes metastatic pulmonary cancer. However, the role of miR-200c in breast cancer is still unknown. Therefore, in this study, miR-200c mimics were transfected into the highly metastatic breast cancer cell line MDA-MB-231. Their invasion and migration abilities were observed by scratch and transwell migration assays. Real-time PCR was used to detect mRNA levels of Foxf2, Zeb1, and E-cadherin, whereas Foxf2 protein level was determined by western blot analysis. Our results showed that, compared to the control group, miR-200c inhibited the migration or invasion of MDA-MB-231 cells. Real-time PCR and western blot analysis exhibited significant decreases in Foxf2 expression in the presence of miR-200c, along with a decrease in Zeb1 and increase in E-cadherin mRNA expressions. Thus, our preliminary data demonstrated that miR-200c could inhibit the metastasis of breast cancer cells by downregulating Foxf2 expression, providing leads for the discovery of a novel breast cancer treatment.

MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint.

OBJECTIVE: This study aimed to screen differential expression of microRNAs (miRNAs), and investigate function of the specifically selected miRNA in synovial fibroblasts from patients suffering osteoarthritis of temporomandibular joint (TMJOA). METHODS: MiRNA microarray was used to select differentially expressed miRNAs between TMJOA and normal synovial fibroblasts. The expression of screened miRNA221-3p was quantified using real-time PCR, and its specific target gene was predicted by bioinformatics. After transfection of miRNA221-3p mimics or inhibitor into synovial fibroblasts, the expression of v-Ets avian erythroblastosis virus E26 oncogene homolog 1 (Ets-1) was detected by immunohistochemistry, real-time PCR and Western blot, respectively. Dual luciferase activity was performed to identify the direct regulation of miRNA221-3p on Ets-1. Interlukin-1ß (IL-1ß) mimics an inflammatory situation. RESULTS: In TMJOA synovial fibroblasts, eight miRNAs were up-regulated and six miRNAs were down-regulated. MiRNA221-3p was the most down-expressed. A sequence in the 3'-untranslated (3'-UTR) of Ets-1 complementary to the seed sequence of miRNA221-3p. Elevated expression of Ets-1 associated with attenuation of miRNA221-3p. Over-expression of miRNA221-3p suppressed the activity of a reporter construct containing the 3'-UTR of Ets-1 transcript and inhibited the expression of Ets-1 as well as its downstream molecules, matrix metalloproteinase 1 (MMP1) and MMP9 in TMJOA synovial fibroblasts. IL-1ß suppressed the expression of miRNA221-3p in both a dose-dependent and time-dependent manner. CONCLUSION: The reduction of miRNA221-3p in synovial fibroblasts, attributed from abundance of IL-1ß in inflamed circumstance, induces Ets-1 up-regulation and then, initiates MMP1 and MMP9 secretion, thereby leading to continuously pathological development in TMJOA.