Objective To investigate the associations of reproductive health indicators with lung function and chronic obstructive pulmonary disease(COPD)among women aged 40 years and above.Methods From Jul to Sep,2021,female subjects aged 40 years and above were randomly selected from the Shanghai Suburban Adult Cohort and Biobank for COPD screening.A questionnaire was used to obtain information on demographic characteristics and reproductive health indicators.Linear regression was used to analyze the effects of reproductive health indicators on forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1).Logistic regression was also used to analyze the effects of reproductive health factors on FVC as a percentage of the predicted value(FVC%Pred)and FEV1%Pred as well as on COPD.Results A total of 1876 women aged 40 years and above were enrolled with mean age of(62.1±8.2)years old,among them,78.1%were menopausal,and 40.9%had been pregnant≥3 times.Multivariate analysis showed that FVC and FEV1 decreased in postmenopausal women,but menopause was not associated with a decrease in their percentage of predicted values.Pregnancies≥3 times was a risk factor for COPD(for 3 times,OR=4.92,95%CI:1.48-19.95,P<0.05;for≥4 times,OR=9.06,95%CI:2.32-41.57,P<0.01),while pregnancies of 2 times did not increase the risk of COPD.Conclusion In women aged 40 years and above,menopause is associated with poorer FVC and FEV1,and excessive pregnancy(≥3 times)is a risk factor for COPD.

Objective To discuss the evaluation basis of the clinical rational use of Dahuang Zhechong Capsule and to establish its rationality evaluation criterion to promote the sensible use of Dahuang Zhechong Capsule.Methods The rationality evaluation criterion for Dahuang Zhechong Capsule was formulated by referring to the package insert,treatment guidelines,and other literature.According to the criterion,270 outpatient prescriptions using Dahuang Zhechong Capsule in Xiyuan Hospital,China Academy of Chinese Medical Sciences were reviewed from January to June 2020.The indication,usage and dosage,drug combination,and repeated administration were analyzed.The pharmaceutical intervention was performed to address the problems found in the prescription reviews,and 328 outpatient prescriptions using Dahuang Zhechong Capsule in October 2020 were reevaluated.Results The irrational use rate of Dahuang Zhechong Capsule from January to June 2020 was 42.22％(114 cases),including 108(40％)cases of inappropriate indications,five(1.85％)cases of improper usage and dosage,and one(0.37％)case of inappropriate administration route.However,the pharmaceutical intervention in October 2020 remarkably reduced the irrational use rate of Dahuang Zhechong Capsule(4.27％,14 cases),all of which were inappropriate indications.Conclusion Dahuang Zhechong Capsule is being used irrationally;therefore,establishing an evaluation criterion is required.The specific situation of irrational drug use can be identified by prescription review according to its rationality evaluation criterion to manage its clinical use better and promote its rational use.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Objective:To investigate mutations in the KRT5 gene in a pedigree with Dowling-Degos disease.Methods:Clinical data were collected from the proband, and a survey was conducted in 12 members in 3 generations of the family. Peripheral blood samples were obtained from the proband, 8 family members and 50 unrelated healthy individuals, genomic DNA was extracted for whole-exome sequencing, and sequencing results were compared with the published sequences of human KRT5, POFUT1 and POGLUT1 genes.Results:There were 3 patients in this family, including the proband, his father and deceased grandmother. The proband and his father clinically presented with reticular pigmentation in the skinfolds, especially the chest and abdomen skinfolds. A novel heterozygous nonsense mutation c.165T>A was identified in exon 1 of the KRT5 gene in the proband and his father, but not in other family members or healthy controls. No abnormality was found in the POFUT1 or POGLUT1 gene in any subjects.Conclusion:A novel heterozygous nonsense mutation c.165T>A was identified in the KRT5 gene, and may contribute to the clinical phenotype of the proband and his father with Dowling-Degos disease.

Objective:To report 8 patients of sporadic Creutzfeldt-Jakob disease (sCJD) with real-time quaking-induced conversion (RT-QuIC) positive and analyze their clinical characteristics.Methods:The medical records of patients discharged from Henan Provincial People′s Hospital from January 2018 to May 2021 who were diagnosed with clinically probable sCJD and had RT-QuIC test were retrospectively analyzed. General information (gender, age, initial symptom, main clinical manifestations), accessory examination [brain magnetic resonance imaging (MRI), electroencephalogram, cerebrospinal fluid 14-3-3 protein, prion protein gene, antibodies related to autoimmune encephalitis and paraneoplastic syndrome] were collected. By a telephone-based follow-up survey, data about morality and total duration of course were collected. The patients were divided into two groups according to electroencephalogram, 14-3-3 protein, duration of disease and MRI results, and the differences of fluorescence peak time and fluorescence peak value in RT-QuIC results between groups were compared.Results:Among 8 patients, 7 patients had subacute onset and 1 patient had chronic onset. Main clinical manifestations included progressive cognitive decline (8/8), pyramid sign (5/8), walking instability (4/8), mental and behavior disorder (4/8), myoclonus (4/8), akinetic mutism (4/8), dizziness (3/8), limb shaking (2/8), dysarthria (2/8), visual hallucination (1/8), impaired vision (1/8). All cases had abnormal electroencephalogram and typical periodic sharp slow compound waves (PSWCs) were observed in 5 cases. Brain MRI showed high signal intensity in the cerebral cortex and/or basal ganglia on diffusion-weighted imaging in 7 cases, of which 6 cases involved bilateral basal ganglia. Cerebrospinal fluid 14-3-3 protein was positive in 2 cases, and RT-QuIC was positive in all cases. The fluorescence peak time of RT-QuIC was shorter in patients with PSWCs [(7.617±2.164) h vs (10.602±2.247) h, t=2.84, P=0.010] and high total MRI score [ (7.600±1.907) h vs (9.760±2.457) h, t=2.26, P=0.032]. Conclusions:RT-QuIC detection is a reliable method for early diagnosis of sCJD. RT-QuIC results were related to PSWCs and degree of MRI involvement.

Objective:To summarize the clinical and imaging features of 10 patients with genetically diagnosed neuronal intranuclear inclusion disease (NIID) to avoid clinical misdiagnosis and mismanagement of NIID.Methods:Ten patients with NIID, admitted to our hospital from January 2020 to March 2022, were chosen in our study. All patients were confirmed as having NIID by NOTCH2NLC gene assay. Their clinical data, gene detection results and skin pathological results were collected and anlyzed. Results:These patients aged from 57 to 84 years, including 8 females. The episodic symptoms as main symptoms were noted in 6 patients, including 3 patients with encephalopathy, 1 patient with TGA, 1 patient with stroke-like episode, and 1 patient with migraine-like symptoms. Chronic progressive symptoms as main symptoms were noted in 4 patients, including 3 patients with dementia and 1 patient with Parkinson's disease. There were characteristic linear hyper-intensities in diffusion weighted imaging (DWI) in the corticomedullary junction predominantly in the frontal lobes. White matter lesions appeared in T2 Flair might have been noted years before lesions appeared in DWI, with wider ranges. All had GGC repeated expansion in NOTCH2NLC gene in non-coding area, with mutation number>60. Skin biopsy was performed in 6 patients, showing the formation of intranuclear inclusion bodies in different cells; and ubiquitin and P62 were found positive in immunohistochemical staining. Conclusions:NIID patients have large clinical heterogeneity; most patients have episodic symptoms as main manifestations, often accompanied by chronic progressive symptoms; stroke attack and migraine are rare clinical phenotypes of NIID. The high signal at the cortical medullary junction in DWI is a characteristic imaging change.

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein δ (CEBPδ) mRNA, miR-3553 and rno-Acad8_0002 regulate the hepatocytes in G

Objective To explore the pathways and patterns which CCAAT enhancer binding proteina (CEBPα) mRNA, miR-144-3p, rno-LOC100365958_0001, rno-Usp3_0010 and rno-AC241873_0010 regulate the hepatocytes in G

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein ζ (CEBPO mRNA, miR-136-3p, rno-Crebrf_0009, rno-Slc38a9_0001, rno-LOCl00362999_0001 and rno- Got1_0001 regulate the hepatocytes in G

Objective In order to meet the needs of maxillofacical bone defect repair, the aim of this study was to synthesize graphene oxide(GO) modified three-dimensional conneted nano- zirconia(ZrO₂) bone tissue engineering scaffold and evaluate its surface morphology, compressive strength and cytocompatibility. Methods GO was synthesized by a modified Hummers method and then was testified by scanning electron microscope, transmission electron microscopy and fourier transform infrared spectroscopy. ZrO₂ scaffold was modified by different concentrations(0.5,1.0,1.5mg/mL) of GO dispersion via a silane-mediated method. The composite scaffold with uniform GO coating was chosen for compressive strength test and co-cultured with human dental pulp stem cells(hDPSCs). Actin staining was used to observe the growth of the cells on the scaffold, and MTS was used to detect the cell activity. Results The characterization results showed that, under scanning electron microscope, the GO was flaky and the surface morphology of folds could be seen. Part of the GO layer folds up at the edge. Under transmission electron microscopy, the GO was clearly observed to have a gossylike, translucent and slightly wrinkled lamellar structure. The crystal structure in this area in the high-resolution filter image showed a six-member ring structure like graphite. Under high power electron microscope, the 1.0mg/ml GO-ZrO₂ scaffold could be seen to deposit a thin layer of GO at the crack of the scaffold skeleton, connecting the two ends of the crack, and lamellar GO with folds could be observed on the surface of ceramic particles. The comparison of mechanical properties showed that the compression strength of GO-ZrO₂ scaffold was sgnificantly increased compared with that of ZrO₂ scaffold[（1.292±0.087）vs（1.031±0.076）, P<0.05]. Compared with the simple ZrO₂ scaffold, the GO-ZrO₂ scaffold showed more dense extension and adhesion to the surface of scaffolds, showing more active cell proliferation. The cell viability test showed that the viability of hDPSCs was significantly improved on GO-ZrO₂ scaffold after 1, 3 and 5 days of proliferation compared with the simple ZrO₂ scaffold(P<0.05). Conclusion The ZrO₂ scaffold modified by GO improved compressive strength, promoted the early proliferation of hDPSCs with good cytocompatibility.