Objective To analyze the association of polymorphisms of estrogen receptor (ER) α and β genes with systemic lupus erythematosus (SLE) in Chinese Han cohort of Yunnan Province.Methods XbaⅠ and Pvu Ⅱ of ERα gene,Rsa Ⅰ and Alu Ⅰ of ERβ gene were typed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 697 SLE patients and 638 healthy controls.The frequency distribution of the alleles and genotypes were analyzed by Hardy-Weinberg equilibrium test and x2 test.Results ① For ERα gene,the frequency of minor allele of Pvu Ⅱ C in SLE patients was significantly higher than healthy controls (x2=15.427,P=0.001);the allele frequencies of XbaⅠ in SLE patients showed no significant difference compared with healthy controls (P＞0.05).The frequency of minor genotype of Pvu Ⅱ CC in SLE patients was significantly higher than healthy controls (x2=17.371,P=0.011).The frequency of two locus haplotype AATT in SLE patients was significantly lower than healthy controls (x2=6.333,P=0.012);the frequency of the two locus haplotype AACC in SLE patients was significantly higher than healthy controls (x2=7.771,P=0.038).② For ERβ gene,the frequency of minor allele RsaⅠ A in SLE patients was significantly lower than healthy controls (x2=12.595,P=0.013);the allele frequencies of Alu Ⅰ in SLE patients showed no significant differences compared with the healthy controls (P＞0.05).The frequency of minor genotype AA of Rsa Ⅰ in SLE patients was significantly higher than healthy controls (x2=41.456,P=0.000).The frequency of two locus haplotype AAGG in SLE patients was significantly higher than healthy controls (x2=37.063,P=0.000).The frequency of the two locus haplotype AAGA in SLE patients was significantly lower than healthy controls(x2=21.086,P=0.001).③ Pvu Ⅱ C was related with splenomegaly (x2=4.212,P＜0.05).The two locus haplotype AGTC of Xba Ⅰ and Pvu Ⅱ was related with edema (x2=7.898,P＜0.05).Conclusion There are associations between the polymorphisms of ERα and ERβ genes and SLE.The ERα and ERβ genes may be the susceptible genes for SLE in Yunnan Han Chinese Cohort.

A device for promoting normal locomotor activity recuperation was made, which was composed by frame, elastic bolt and normal gait mark carpet. The device has the effects of weight relieving, abnormal gait preventing, and safeguards providing. The patient could do gait training by he/her self or assistant self training under the weight reducing and protecting of the device in order to improve the walking ability and the normal gait formation. It is effective for preventing drop foot and leg adduction, and also helpful for the recovery of normal gait ability and the prevention of abnormal gait formation. It is applicable for the patient who can not be trained with ordinary weight relief walking training, such as severe cerebral palsy and severe spasmodic lower extremity and foot drop after brain injury. The results demonstrated that the device is effective in protecting, correcting, preventing abnormal gait as well as forming normal gait.

Objective To develop one kind of device that can not only reduce the body weight,but also provide a good condition for training lower extremity potentialities.Methods The body weight bearing support and protection system,body weight reducing system and scaled footboard were made respectively.The lower extremity potentialities,nervous conduction speed and leg motion coordination ability training were done under protection and body weight reducing.Results The potential training device could exactly protect the patient and reduce body weight,and make the training step by step.Under the effects of protecting and body weight reducing of the potential training device,the training could be performed together with the Chinese traditional medicine rehabilitation method;that was physical and breathing exercises.The lower extremity potentialities were developed nicely.Conclusion The lower extremity potentialities training device is a useful training device which can bear body weight,have protective effect,develop lower extremity potentialities and improve coordination ability of lower extremities.

Glaucoma is an irreversible blinding eye disease caused by the structural and functional damage of optic nerve induced by pathological increase of intraocular pressure (IOP), characterized by multiple causes and strong heterogeneity.The control of IOP to reduce the risk of optic damage has been the main therapeutic strategy of glaucoma for many years.However, in clinical experience, some patients show progress of optic nerve damage despite the effectively controlled IOP, the mechanism of non-IOP-dependent secondary damage is still an urgent problem to be solved and a research hotspot in the pathogenesis of glaucoma.With the continuous innovation of molecular biological technology, breakthroughs have been made in the field of basic research.Partial visual recovery can be boosted by alleviating local immune and inflammatory responses.Due to a lack of symbolic clinical application results, it has become an immediate priority to attach importance to the combination of basic clinical research and facilitate the transformation of results.Starting from the theory of glaucoma-immune inflammation, understanding the importance of the immune homeostasis of eyes, paying close attention to the linkage of eyes and brain in physiopathological process and the progression of diseases in the whole visual pathway, and fully understanding and effectively making good use of the opportunities and implications brought by new techniques will have significant effect in formulating clinical diagnosis and treatment plans.

The immune and inflammatory response is a defense response of the body to stimuli and can be divided into infectious and non-infectious immunoinflammatory diseases.Current advances in research on immunoinflammatory in the eye focus on two main areas: research on targeted drugs or targeted molecular therapies for classical immunoinflammatory ocular diseases, and research on the immune mechanisms of previously considered non-immunoinflammatory ocular diseases.Key molecules of immunoinflammation in the pathogenesis of classical ocular immune diseases such as allergic conjunctivitis, immune keratopathy, non-infectious uveitis, optic neuritis, and thyroid-associated ophthalmopathy are important targets for biological therapy.Immunoinflammatory mechanisms have also been found to have an integral regulatory role in infectious ocular diseases and ocular tumors in recent years.More importantly, recent studies have revealed that immunity also plays an important role in the promotion of traditionally considered non-immunoinflammatory ocular diseases such as myopia, glaucoma, cataract, and age-related macular degeneration.Thus, immunoinflammation is widely involved in the development of diseases from the anterior to the posterior segment of the eye, and research related to the immunotherapy of related ocular diseases through the modulation of immunoinflammation has attracted the attention of the global ophthalmic community.Ophthalmologists should pay attention to the mechanisms of immune modulation and the progress of immunotherapy in various ophthalmic diseases, and explore new strategies for better guidelines for the treatment of ocular immunoinflammatory diseases.

OBJECTIVE: To develop a self deep breathing training device which can improve lung function compliance and blood oxygen saturation. METHODS: The device consists of four parts:flow tube, measuring cylinder, mobile phone holder and meridian guidance audio-visual synthesis training software. The flow tube measures the flow rate of inhaled gas, the metering cylinder measures the total amount of inhaled gas, and the mobile phone rack is equipped with a mobile phone storing the meridian guidance audio-visual synthesis training software. RESULTS: The device is reasonable in structure and flexible in operation, which can meet the requirements of self deep inspiration training under the guidance of training module. CONCLUSIONS Deep inspiration training under the guidance of guidance training module can form "deep and slow" abdominal breathing, and then improve lung function.
Cell Phone ; Lung ; Meridians ; Software

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Aging ; Animals ; Autoimmune Diseases ; Disease Models, Animal ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism* ; Mice ; Mice, Inbred C57BL ; Th17 Cells/metabolism* ; Uveitis/pathology* ; Virulence

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

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