This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Objective:To investigate the clinical characteristics and prognostic factors of 2019 novel coronavirus (2019-nCoV) Omicron variant infected cases.Methods:A total of 987 coronavirus disease 2019 (COVID-19) adult imported cases admitted to Shanghai Public Health Clinical Center, Fudan University from July 1, 2021 to January 6, 2022 were recruited. The cases were divided into Omicron group (193 cases) and non-Omicron group (794 cases) according to the genotype of the virus. The clinical data, imaging examination and laboratory results of two groups were collected and compared. Chi-square test and Mann-Whitney U test were used as statistical methods. Multiple linear regression analysis was used for multiple linear regression analysis. Results:The majority of patients in Omicron group were 18 to 30 years old, accounting for 51.3%(99/193), which was higher than 31.4%(249/794) in non-Omicron group. The difference was statistically significant ( χ2=52.75, P<0.001). The proportion of mild cases in Omicron group was 88.6%(171/193), which was higher than 81.6%(648/794) in non-Omicron group. The difference was statistically significant ( χ2=5.37, P=0.021). Cases with symptoms were more common in Omicron group than those in non-Omicron group (60.1%(116/193) vs 29.1%(231/794)), and the difference was statistically significant ( χ2=65.49, P<0.001), with the main clinical manifestations of sore/itchy throat, fever and cough/expectoration. The proportion of cases with pulmonary computed tomography (CT) imaging manifestations at admission in Omicron group was 13.0%(25/193), which was lower than that in non-Omicron group (215/794, 27.1%). The difference was statistically significant ( χ2=16.83, P<0.001). The proportion of cases with 2019-nCoV IgG positive at admission was 47.7%(92/193) in Omicron group, which was lower than 61.1%(485/794) in non-Omicron group, and the difference was statistically significant ( χ2=11.51, P<0.001). The hospitalization time of Omicron group was 20.0 (16.0, 23.0) d, which was longer than that of non-Omicron group (14.0 (10.0, 22.0) d), and the difference was statistically significant ( Z=-7.42, P<0.001). Multiple linear regression analysis showed that the time of hospitalization of cases with 2019-nCoV IgG positive at admission was shorter, while that of the cases with fever in Omicron group was longer (both P<0.050). Conclusions:The main clinical characteristics of cases with Omicron variant are fever and upper respiratory symptoms. Their pulmonary CT imaging manifestations are less, and the time of hospitalization is slightly longer. The time of hospitalization and the virus clearance time in Omicron variant infected cases with 2019-nCoV IgG positive at admission and not presented with fever are both shorter.

The purpose of this study was to explore the differences in interhemispheric functional connectivity in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) based on a triple network model consisting of the default mode network (DMN), salience network (SN), and executive control network (ECN). The technique of voxel-mirrored homotopic connectivity (VMHC) analysis was applied to explore the aberrant connectivity of all patients. The results showed that: (1) the statistically significant connections of interhemispheric brain regions included DMN-related brain regions (i.e. precuneus, calcarine, fusiform, cuneus, lingual gyrus, temporal inferior gyrus, and hippocampus), SN-related brain regions (i.e. frontoinsular cortex), and ECN-related brain regions (i.e. frontal middle gyrus and frontal inferior); (2) the precuneus and frontal middle gyrus in the AD group exhibited lower VMHC values than those in the aMCI and healthy control (HC) groups, but no significant difference was observed between the aMCI and HC groups; and (3) significant correlations were found between peak VMHC results from the precuneus and Mini Mental State Examination (MMSE) and Montreal Cognitive Scale (MOCA) scores and their factor scores in the AD, aMCI, and AD plus aMCI groups, and between the results from the frontal middle gyrus and MOCA factor scores in the aMCI group. These findings indicated that impaired interhemispheric functional connectivity was observed in AD and could be a sensitive neuroimaging biomarker for AD. More specifically, the DMN was inhibited, while the SN and ECN were excited. VMHC results were correlated with MMSE and MOCA scores, highlighting that VMHC could be a sensitive neuroimaging biomarker for AD and the progression from aMCI to AD.
Aged ; Aged, 80 and over ; Alzheimer Disease/physiopathology* ; Brain/diagnostic imaging* ; Brain Mapping ; Cognitive Dysfunction/physiopathology* ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Memory ; Middle Aged ; Models, Neurological ; Nerve Net

PURPOSE: Myeloid differentiation-2 (MD-2) has been associated with endotoxin and inflammatory disorders because it can recognize lipopolysaccharide (LPS) binding and attenuate Toll-like receptor 4 (TLR4)-mediated signaling. However, its role in allergic inflammation has yet to be clarified. We examined whether single nucleotide polymorphisms (SNPs) in MD-2 promoter can affect MD-2 expression and aimed to clarify the relationship between Der p 2 allergy and SNPs of MD-2 promoter. METHODS: The function of SNPs of MD-2 promoter and the effects of cytokines and immunoglobulin on the secretion and mRNA expression were investigated in 73 allergic subjects with different MD-2 gene promoter variants. Peripheral blood mononuclear cells were cultured with or without LPS in the presence of Dermatophagoides pteronyssinus group 2 allergen (Der p 2), followed by mRNA extraction and cytokine expression analysis. The culture supernatants were collected for cytokine measurement. RESULTS: Patients with the MD-2 promoter SNPs (rs1809441/rs1809442) had increased mRNA expressions of MD-2, epsilon heavy chain of IgE (Cepsilon), and interleukin (IL)-8; however, only MD-2 and IL-8 were further up-regulated after Der p 2 stimulation. Patients with SNPs of MD-2 promoter tended to have high levels of IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha after Der p 2 and LPS stimulation. Increased secretions of IL-6, IL-8, and IL-10 were found to be up-regulated by Der p 2 stimulation, and an increased secretion of IFN-gamma and decreased secretion of IL-4 were noted after LPS stimulation. CONCLUSIONS: The high levels of proinflammatory cytokines secreted by Der p 2 were predetermined by MD-2 promoter SNPs (rs1809441/rs1809442). Through cytokine secretion by Der p 2 and LPS, these SNPs may serve as an indicator of the pathological phenotype of Der p 2-induced allergic inflammation.
Cytokines ; Dermatophagoides pteronyssinus ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunoglobulins ; Inflammation* ; Interleukin-10 ; Interleukin-4 ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Phenotype ; Polymorphism, Single Nucleotide ; RNA, Messenger ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha

A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules.
Animals ; Capsules ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Panax notoginseng ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology

BACKGROUNDExhaled nitric oxide (NO) is a noninvasive biomarker of airway inflammation in pulmonary diseases. Hydrogen sulfide (H2S), as the third member of the gasotransmitter family, is involved in the pathophysiological process in lung diseases. H2S also exists in exhaled breath and can be sampled non-invasively. The study investigated the level of exhaled H2S in patients with chronic obstructive pulmonary disease (COPD) and its correlation with exhaled NO.

METHODSLevels of exhaled NO and H2S, lung function, and cell differential counts in induced sputum were studied in 19 patients with acute exacerbation of COPD (AECOPD), 19 patients with stable COPD and seven healthy smoke controls.

RESULTSExhaled H2S levels were similar in patients with AECOPD (10.0 parts per billion (ppb), 8.0-13.0 ppb), stable COPD (10.0 ppb, 9.0-12.0 ppb), and healthy controls (9.0 ppb, 8.0-16.0 ppb) (P > 0.05). Exhaled NO levels were similar in patients with AECOPD (155.0 ppb, 129.0-190.0 ppb), stable COPD (154.0 ppb, 133.0-175.0 ppb) and healthy controls (165.0 ppb, 112.0-188.0 ppb) (P > 0.05). Exhaled H2S levels correlated positively with exhaled NO in all healthy controls and patients with COPD (r=0.467, P < 0.01). No significant correlation was found between the exhaled H2S level and percentage of predicted FEV1 (P > 0.05) and proportion of different cell types in induced sputum (P > 0.05).

CONCLUSIONSThere is a correlation between exhaled H2S and exhaled NO. The role of exhaled H2S in airway inflammation in COPD still needs further investigation.

Aged ; Breath Tests ; Female ; Forced Expiratory Volume ; physiology ; Humans ; Hydrogen Sulfide ; metabolism ; Male ; Middle Aged ; Nitric Oxide ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; physiopathology

OBJECTIVEThe objective of this study is to investigate the influence of zirconia content which is 0-30.0% weight percentage of matrix on translucency of zirconia-toughened alumina glass-infiltrated ceramics.

METHODSSeven groups were divided according to different weight percentage of zirconia (0, 2.5%, 5.0%, 7.5%, 10.0%, 20.0% and 30.0%). After sintering, infiltrating and polishing, spectral transmittance was determined with spectrophotometer under D65 standard source. Contrast ratio was also tested by whiteness colorimeter.

RESULTSWith mass fraction of zirconia increasing from 0 to 30.0%, spectral transmittance reduced from 0.406% to 0.058%, while contrast ratio value increased from 0.849 +/- 0.005 to 1.015 +/- 0.006. When zirconia content was 10.0%, contrast ratio was 0.990 +/- 0.008. When it was more than 10.0%, transmission rate of the downward trend and contrast ratio of the rising trend became flat.

CONCLUSIONZirconia content has a direct impact on translucency of zirconia-toughened alumina glass-infiltrated ceramic, which is essentially opaque when zirconia content is 10.0%. When mass fraction of zirconia is more than 10.0%, the influence of zirconia content is reduced.

Aluminum Oxide ; Ceramics ; Dental Materials ; Dental Porcelain ; Glass ; Zirconium

Objective To study the effects of alumina content on sintered density, mechanical property and translucency of zirconia nanocomposite all-ceramics. Methods Specimens of zirconia nanocomposite all-ceramics were divided into five groups based on their alumina content which are 0% (control group), 2. 5% , 5. 0% , 7. 5% and 10. 0% respectively. The sintered densities were measured using Archimedes' method. Specimens' bending strengths were measured with three-point bending test( ISO 6872). The visible light transmittances were measured with spectrophotometric arrangements and the fractured surfaces were observed using scanning electron microscope (SEM).Results The control group of pure zirconia could be sintered to the theoretical density under pressure-less sintering condition. The bending strength was (1100.27 ±54.82) MPa, the fracture toughness was (4.96 ±0.35) MPa·m1/2 and the transmittance could reach 17. 03%. The sintered density and transmittance decreased as alumina content increased from 2. 5% to 10%. However, the fracture toughness only increased slightly. In all four alumina groups, the additions of alumina had no significant effect on samples' bending strengths (P >0. 05). When the content of alumina was 10% , fracture toughness of specimens reached (6. 13 ±0.44) MPa·m1/2 while samples' transmittance declined to 6. 21 %. SEM results showed that alumina particles had no significant effect on the grain size and distribution of tetragonal zirconia polycrystals. Conclusions Additions of alumina to yttria-tetragonal zirconia polycrystals could influence its mechanical property and translucency. Additions of the other phase to zirconia ceramics should meet the clinical demands of strength and esthetics.

Objective To prepare a novel apatite-wollastonite bioactive glass-ceramic-calcium sulphate hemihydrate(AW-BGC-CSH) composite,to study its biocompatibility,and to provide experimental support for its further clinical application.Methods Samples of AW-BGC-CSH composite were prepared with different AW-BGC granules-CSH ratios (50%,40%,30%,20%).Surface morphology,microstructure and mechanical features of the composite were measured.Osteoblasts were cultivated in vitro on the composite.Cell morphology,proliferation,and the alkaline phosphatase(ALP) activity of osteoblasts were examined to determine the biocompatibility of the composite.Results The composite showed a threedimensional pored structure with communicated micropores under scanning electron microscopy(SEM).The plasticity of the composite could be maintained within 3-5 min.Its top solidification temperature was 36.4 ℃and the maximum compressive strength was 9.3 Mpa.The osteoblasts adhered to the composite and grew well.At 1,3,5,7 d after cultivated,the microprotein contents of the composite were (251±12),(296±31),(580±13) and (571±15)mg/L,and the ALP activity of the composite were (4.50±0.68),(6.90±0.27),(12.05±0.28) and (11.86±0.63) U/mg.The results of the ALP activity and microprotein contents in the experiment group were significantly higher than those in the control group(P <0.05).Conclusions The prepared AW-BGC-CSH composite has a three-dimensional pored structure,favourable plasticity,mechanical property and good biocompatibility.

OBJECTIVETo investigate the effects of Sol-Gel coating on the corrosion resistance of nickel-chronium alloys in vitro.

METHODSThe bond strength of coating-substrate interface sintered at different temperatures (300, 400, 500, 600 degrees C) was tested by scratching method. The Sol-Gel coating was analyzed by scanning electron microscope (SEM), and its corrosion resistance was assessed by a static immersion method.

RESULTSThe bond strength of coating-substrate interface reaches the peak at 400 degrees C. The Sol -Gel coating can apparently inhibit the release of metal ions and improve the corrosion resistance of nickel-chromium alloy.

CONCLUSIONSol-Gel coating can evidently improve corrosion resistance of the nickel-chromium alloy, which has great potential in prospective clinical practice.

Alloys ; Chromium Alloys ; Corrosion ; Dental Alloys ; Humans ; Nickel ; Polymethyl Methacrylate ; Prospective Studies