Abstract: Upon monitoring cytoplasmic aberrant double-stranded DNA, cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines, which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection. However, sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases, aging-associated inflammation, and neurodegenerative pathologies. Herein, we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases, with a particular review of the research and development progress of STING agonists, cGAS inhibitors, and STING inhibitors, aiming to provide some theoretical reference for the future development of cGAS-STING modulators.

Bilateral vestibulopathy（BVP） is one of the common diseases in the vestibular nervous system, with an incidence rate of about 4%-7% in the population, which can lead to a variety of body dysfunctions. At present, there are two main treatment methods for BVP. One is vestibular rehabilitation. However, only part of BVP patients can finally benefit from vestibular rehabilitation, and most patients will remain with permanent vestibular dysfunction. Benefiting from the maturity of cochlear implant technology, European and American countries took the lead in the development of vestibular prosthesis（VP） technology to restore the vestibular function in patients with BVP. This review will focus on the development history, principles, future applications and the related research progress of VP in China.
Humans ; Bilateral Vestibulopathy/therapy* ; Cochlear Implants ; Vestibule, Labyrinth ; Cochlear Implantation ; China

Dizziness or vertigo is a common clinical symptom, and its underlying etiology is complex. Many clinicians are confused about its diagnosis and treatment. This article presents a case about chronic vestibular syndrome. And case appreciation and academic discussion are conducted by well-known domestic neurologists and otologists, so as to provide a good thinking model and basic ideas for the diagnosis and treatment of dizziness or vertigo, hoping to further improve the diagnosis and treatment level among clinicians.
Humans ; Dizziness/therapy* ; Vertigo/etiology* ; Vestibular Diseases/complications* ; Otolaryngologists

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome

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Objective:To investigate the peripheral blood inflammatory markers including white blood cell count (WBC), monocytes, neutrophils, lymphocytes, platelets, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), high-density lipoprotein(HDL-C), low-density lipoprotein and fibrinogen (FIB) in Ménière′s disease (MD) patients with and without migraine, and to explore the relationship between the inflammatory response with MD and migraine.Methods:The general physical condition, clinical manifestations, pure-tone audiometry, and peripheral blood inflammatory markers of 92 unilateral MD patients who were hospitalized in Peking University People′s Hospital for surgical treatment from January 2017 to January 2021 were continuously collected. Meanwhile, 50 healthy controls matched with age and sex were included, and their general physical conditions and peripheral blood inflammatory markers were also collected. This study consisted of two parts. First, the differences in epidemical characteristics and peripheral blood inflammatory markers between MD patients and healthy controls were compared by univariate analysis. Second, all 92 MD patients were divided into two subgroups according to whether they were accompanied by migraine. The clinical characteristics and peripheral blood inflammatory markers of MD patients with and without migraine were compared by univariate analysis. Thereafter, binary Logistic regression was used to analyze the related factors of whether MD patients were accompanied with migraine.Results:Compared with the healthy control group, the peripheral blood WBC, neutrophils and FIB of MD patients were significantly increased (all P<0.05). Compared with MD patients without migraine, MD patients with migraine had higher female prevalence, longer disease history, lower low-frequency hearing threshold, higher frequency of vertigo attacks and higher HDL-C levels (all P<0.05), meanwhile, female, frequency of vestibular attacks and HDL-C were independent related factors of whether MD patients were accompanied with migraine. Conclusion:The occurrence of MD and migraine may be related to the inflammatory response. The level of anti-inflammatory factors in the blood of MD patients with migraine are higher, suggesting that the inflammatory response status of MD patients with and without migraine is different.

Objective: To construct the mmu-miR-155 eukaryotic overexpression vector pmR-155 and to investigate its effect on HBV replication and expression of PTEN in vivo. Methods: The mmu-mir-146a precursor gene fragment pre-mmu-mir-146a was amplified by PCR, then connected to the pmR-mCherry plasmid vector after double enzyme digestion, the accuracy of recombinant vector was verified by colony PCR、double enzyme digestion and sequencing; then the recombinant vector was transfected HBV transgene mice(Experimental Group)with hydrodynamics-based injection via vena caudalis, and pmR-mCherry plasmid、PBS were respectively transfected into the mice as Empty plasmid Group、Blank Group. The concentration of IFN-γ in the serum was detected by ELISA. The expression of SOCS1、PTEN mRNA in the liver was detected by qPCR at 30d post-transfectioned. The Western blot was performed to detect the changes in SOCS1、PTEN、HBX in the liver tissue at 30 d post-transfectioned. The results were analyzed with Student’s t-test, or one-way analysis of variance and the least significant difference test. Results: the colony PCR、double enzyme digestion and sequencing verified that the gene was inserted into the pmR-mCherry vector. Compared with Blank Group, the expression of miR-155 in the Experimental Group was significantly increased(t = 8.90, P < 0.01); the concentration of IFN-γ in the Experimental Group was significantly increased(F = 26.58, P < 0.01); the mRNA(F_{SOCS1 mRNA} = 19.72, P < 0.01; F_{PTEN mRNA} = 7.38, P < 0.05) and protein(F_SOCS1 = 50.30, P < 0.01; F_PTEN = 129.00, P < 0.01) expression of COCS1、PTEN was significantly decreased in the Experimental group and the protein of HBX was also significantly(F_HBX = 77.97, P < 0.01). Conclusion The pmR-155 eukaryotic overexpression vector is successfully constructed, this recombinant vector can express miR-155 stably; miR-155 can down-regulate cocs1、PTEN gene expression and up-regulate the expression of IFN-γ, it can inhibit the replication of HBV and a potential targets to treating hepatocellular carcinoma.

Objective Using zebrafish to analyze the effect of water temperature on the recovery of spinal cord in-jury. To detect the cell proliferation and changes of gene expression at the injury site during the process of recovery. Meth-ods Surgical operation was performed to induce spinal cord injury ( SCI) on adult fish. Water at a series of temperature was applied to culture the fish. Swimming ability was adopted to observe the recovery of spinal cord injury following surger?y. Vibration sections and immunohistochemistry were performed to observe the cell number post SCI at different stages. The changes of gdnf and nos gene expression were determined by real?time PCR. Results The water temperature changes from 28℃ to 32℃ did not affect the swimming ability of non?injured and sham?injured fish ( P>0. 05 ) . The swimming ability recovered mostly in 8 weeks post spinal cord injury. At 32℃, the swimming ability recovered faster than at 28℃ or at 30℃(P<0. 05). The cell proliferation increased obviously following spinal cord injury (P<0. 05). The proliferation of cells surrounding the spinal cord in jury was more extensive in SCI fishes incubated in 32℃ water than in 28℃ or 30℃ water ( P<0. 05). Real?time PCR assay showed that gdnf was up?regulated in all groups post SCI at 24 h, and 7 and 14 days (P<0. 05). The nos expression was up?regulated in all groups following SCI in 24 h (P<0. 05) and 7 days. There was no sig?nificant difference between the SCI group and sham?injury group (P<0. 05), while after 14 days, the expression of nos was reduced in the SCI group compared with the sham?injury group (P<0. 05). Conclusions A slight increase of incu?bating water temperature can accelerate the recovery of spinal cord injury in zebrafish.

Objective:To investigate the effect of atorvastatin on the blood lipid and uric acid levels of elderly patients with coronary heart disease complicated with diabetes mellitus.Methods:116 patients with coronary heart disease and diabetes were randomly divided into the control group and the experimental group,58 cases in each group.Both groups of patients were given blood glucose control,blood pressure and other symptomatic treatment.The control group was treated with Aspirin Enteric-coated Tablets 0.3～0.6 g/times,3 times/d,oral,clopidogrel tablets,2 tablets each time,1 time/d,oral,nitroglycerin,0.25～0.5 g/time,3 times/d,with service;the experimental group was given atorvastatin on the basis of control group,10～20 mg/time,1 time/d,treatment for 4 weeks.During the treatment,the dosage was timely adjusted according to the conditions of patients.The serum low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C),triglyceride (TG),total cholesterol (TC),uric acid (UA),glycosylated hemoglobin (HbA1c) levels before and after treatment and the clinical treatment efficiency were observed and compared between two groups.Results:Compared with before treatment,the serum LDL-C,TG,TC,UA,HbA1c levels were decreased ahter treatment in both groups of patients,the HDL-C level was increased (P＜0.05);compared with the control group,the serum LDL-C,TG,TC,UA,HbA1c levels were lower,HDL-C level was higher in the experimental group (P＜0.05);compared with the control group,the effective rate of clinical treatment of the experimental group were higher (P＜0.05).Conclusion:Atorvastatin could effectively reduce the blood glucose,blood lipid,uric acid levels of elderly patients with coronary heart disease complicated with diabetes.