Objective:To investigate potential mechanisms of Niclosamide,a calcium-binding protein S100A4 inhibitor,in regulating inflammatory response of bronchial epithelial cells.Methods:Human bronchial epithelial cells BEAS-2B were cultured in vitro and stimulated by LPS or Niclosamide-pretreatment.Inflammatory cytokines and potential signaling molecules expressions were determined by RT-qPCR and Western blot.Intracellular ROS level was quantified by fluorescent probe.Results:Increased ROS level was observed in LPS-stimulated and Niclosamide-pretreatment cells(P<0.05).Compared with control group,mRNA and protein expressions of S100A4 were increased(P<0.05),TLR4/STAT3,MAPK1/3/SIRT1,NF-κB/IKKβ/p65 mRNA expressions were increased(P<0.05),inflammatory cytokines IL-1β and IL-6,tight junction Occludin and ZO-1 mRNA expressions were increased after LPS-treatment(P<0.05),whereas these genetic expressions were downregulated by Niclosamide-pretreatment(P<0.05),except for TLR4/MAPK1 and NF-κB/IKKβ/p65(P>0.05).Western blot showed that compared with control group,LPS-stimulation promoted protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while downregulated protein expression of Occludin.Compared with LPS group,niclosamide-pretreatment downregulated protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while restored protein expression of Occludin(P<0.05).Conclusion:Calcium-binding protein S100A4 inhibitor Niclosamide can alleviate S100A4 expression and inflammatory response of bronchial epithelial cells,which is poten-tially related to STAT3 or MAPK3/SIRT1 signaling.

Objective:To investigate the effects and mechanisms of exogenous calcium-binding protein S100A4 on prolifera-tion,survival and migration functions of glioma cells.Methods:Pan-cancer dataset was downloaded from UCSC database for the analysis of S100A4 expression and prognosis in pan-cancer,and transcriptome and clinical data of glioma patients were downloaded from CGGA database.Prognosis and progression of S100A4 expression in glioma patients were analyzed by R software.S100A4 protein network interaction of glioma patients were addressed by online analytical tools GEPIA and STRING.Human glioma cell lines(U87 and U251)were cultured in vitro,and the experiment was divided into 3 groups:PBS group,S100A4 group and S100A4+TAK242 group[Resa-torvid(TAK242)was a specific inhibitor of Toll-like receptors 4(TLR4)].Flow cytometry was used to detect proliferation and apopto-sis of glioma cells.Wound healing assay,Transwell assay and clone formation assay were used to detect migration and proliferation ability of U87 and U251 cells,and Western blot was used to detect levels of TLR4 protein and NF-κB related signaling proteins.Results:Bioinformatics results showed that S100A4 was significantly upregulated in multiple tumours(P<0.05),which included glio-blastoma(GBM),lower grade glioma(LGG),stomach adenocarcinoma(STAD),liver hepatocellular carcinoma(LIHC),etc,with poorer prognosis in GBM and LGG.Compared with glioma patients with low expression of S1004,high expression S100A4 in glioma patients had shorter survival and higher degree of WHO classification.In addition,S100A4 protein in glioma patients may interact with Annexin A2(ANXA2),TLR4 and advanced glycosylation end product-specific receptor(AGER)proteins.In cellular experiments,U87 and U251 cells showed enhanced proliferation and migration,and significantly up-regulated levels of TLR4,p-ERK1/2,p-p38 and p-p65 proteins after exogenous S100A4 treatment compared to PBS group(P<0.05),while glioma cells in S100A4+TAK242 group showed weaker proliferation and migration,and lower TLR4,p-p38 and p-p65 protein levels than those in S100A4 group,TLR4,p-ERK1/2,p-p38,p-p65 protein levels were significantly down-regulated(P<0.05).Conclusion:S100A4 may regulate func-tion of glioma proliferation,migration and survival through TLR4/NF-κB signaling pathway.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective:To investigate the pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients with pulmonary opportunistic infections in the local area, and to evaluate the clinical application of metagenomic next-generation sequencing (mNGS) in these patients.Methods:From January to December 2021, AIDS patients with pulmonary infections admitted to Zhongnan Hospital of Wuhan University were enrolled. Their bronchoalveolar lavage fluid (BALF) was subjected to mNGS and coventional pathogen detection.Routine pathogen detection methods included smear, culture, polymerase chain reaction (PCR), and immunochromatographic colloidal gold. Fisher′s exact probability method was used for statistical analysis.Results:A total of 69 patients were included, and all of them were tested positive for mNGS. Among them, 53 cases (76.8%) were positive for fungi and viruses, 40 cases (58.0%) were positive for bacteria (excluding Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM)), six cases were positive for MTB, 11 cases were positive for NTM, and seven cases were positive for other pathogens. Mixed infections with two or more pathogens were found in 89.9%(62/69) of the patients. Among the conventional pathogen detections of BALF, 79.7%(55/69) of the patients were positive for pathogens, including 42 cases positive for Pneumocystis jirovecii PCR, 16 cases positive for BALF culture, nine cases positive for MTB PCR, and five cases positive for Cryptococcus antigen. The total detection rate of mNGS was 100.0%(69/69), which was higher than that of the conventional pathogen detection rate of 79.7%(55/69), and the difference was statistically significant (Fisher′s exact probability method, P<0.001). The specificity of mNGS detection was 88.4%. Combining clinical and two detection methods, the top five pathogens were Pneumocystis jirovecii (62.3%(43/69)), Candida (29.0%(20/69)), MTB (20.3%(14/69)), NTM and Talaromyces marneffei (15.9%(11/69), each). Fifty-three patients (76.8%) had co-infection with virus. Conclusions:The main cause of pulmonary infection in AIDS patients in this area is mixed infection, and Pneumocystis jirovecii is the most common pathogen. mNGS could significantly improve the pathogen detection rate in AIDS patients with pulmonary infections.

Objective:To analyze the clinical features and prognosis factors of aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders related optic neuritis (NMOSD-ON).Methods:An ambidirectional cohort study. From June 1, 2015 to June 1, 2019, 103 patients with AQP4 antibody-positive NMOSD-ON in Department of Neuro-ophthalmology, The First Medical Center of PLA General Hospital were included. All patients of followed-up period were ≥24 months. According to the best corrected visual acuity (BCVA) at the last follow-up, the affected eyes were divided into the low vision group [log of minimum resolution angle (logMAR) BCVA≥1.0] and the non-low vision group (logMAR BCVA<1.0), 66 and 37 cases, respectively. The two groups of patients were compared the genernal clinical characteristics, and the logistic regression model and COX proportional hazard model were used to analyze the relevant factors affecting the patient's visual prognosis and recurrence.Results:Among the 103 cases, 96 cases (93.2%, 96/103) were female; 94 cases (91.3%, 94/103) had unilateral disease; 48 cases (46.6%, 48/103) were the first onset; 85 cases (82.5%, 85/103) were effected by eye pain or orbital pain; 21 cases (20.4%, 21/103) had optic disc edema; 51 cases (49.5%, 51/103) serologically autoimmune antibody test were positive. Orbital magnetic resonance imaging (MRI) was performed in 101 cases. There was no obvious abnormal signal in visual pathways except for 5 cases (5.0%, 5/101); 96 cases (95.0%, 96/101) had abnormal signal in the visual path, and the optic nerve was found in the orbit; 52 cases had abnormal optic nerve in orbital segment (51.5%, 52/101); 37 cases (35.9%, 37/103) recurred within 24 months. The recovery of logMAR BCVA after the first onset and the logMAR BCVA at the first onset, at 6 months of follow-up in two groups were 1.4±1.0, 0.3±0.4, 1.9±0.7 and 0.4±0.5, 2.1±0.6, 0.3±0.4, respectively; and there were statistically significant differences between the two groups of patients at different times ( Z=-4.967,-7.603,-8.027; P<0.001). Logistic regression multivariate analysis showed that recovery of BCVA≥1.0 logMAR after the first onset [odds ratio ( OR)=226.276, P<0.001 ] and the number of attacks ( OR=8.554, P=0.003) were independent risk factors for low vision. Multivariate analysis of the Cox proportional hazards model showed the higher the MRI score [hazard ratio ( HR)=0.588, P=0.007] and plasma exchange ( HR=0.124, P=0.049) in the acute phase were protective factors for recurrence. Conclusions:Vision loss accompanied by eye pain or orbital pain is the main symptom of onset AQP4 antibody-positive NMOSD-ON, a small number of patients have disc edema, 49.5% patients serologically autoimmune antibody test are positive. Abnormal optic nerve signals can be seen in 95.0% of patients in orbital MRI, and 51.5% patients have abnormalities in the orbital optic nerve. The worse the recovery of BCVA after the first onset and the greater the number of attacks are unfavorable factors affecting the prognosis of vision. High MRI scores and plasma exchange in the acute phase are favorable factors to prevent the recurrence of the disease.

Objective:To investigate the epidemic trend and risk change of acquired immunodeficiency syndrome (AIDS) complicated with malignant tumors after combination antiretroviral therapy (cART).Methods:The types of malignant tumors in patients with AIDS at different stages of cART were analyzed among anti-human immunodeficiency virus (HIV)-positive population in Hubei Province screened in National AIDS/HIV prevention and control information system from 1st January, 2004 to 31st December, 2018. The standardized incidence ratios(SIR) of malignant tumors in AIDS patients was analyzed based on the incidence of malignant tumors in the general population in Hubei Province or China in 2013. The changes in risks for development of malignant tumors in AIDS patients at different cART stages from 2004 to 2013 and 2014 to 2018 were compared.Chi-square test was used for statistical analysis.Results:Three hundred and twenty-three out of 22 994 AIDS patients were diagnosed with malignant tumors. Non-Hodgkin lymphoma(NHL) and cervical cancer were most common types in acquired immunodeficiency syndrome-defining cancers (ADC), while liver cancers and lung cancers were the most common types in non-acquired immunodeficiency syndrome-defining cancers (NADC). The overall risk of malignancy in AIDS patients was similar to that in the general population (SIR=1.06, χ2=0.62, P=0.426). However, the risks of Kaposi sarcoma, NHL, Hodgkin lymphoma, cervical cancer, and head and face cancers (excepting nasopharyngeal cancer) in AIDS patients were significantly higher than those in the general population (SIR=834.09, 9.65, 13.33, 5.22 and 2.94, respectively, χ2=11 747.27, 625.54, 56.65, 184.21 and 13.66, respectively, all P<0.01). The risks of lung cancer, colorectal anal cancer, stomach cancer and breast cancer in AIDS patients were significantly lower than those in the general population (SIR=0.33, 0.36, 0.43 and 0.45, respectively, χ2=33.43, 12.84, 9.01 and 7.21, respectively, all P<0.05). The SIR of cervical cancer, liver cancer and colorectal anal cancer from 2014 to 2018 were 4.06, 0.43 and 0.10, respectively, which were significantly lower than those from 2004 to 2013 (7.42, 1.96 and 0.84, respectively). The differences were all statistically significant ( χ2=5.39, 19.52 and 10.86, respectively, all P<0.05). Conclusions:At present, there are no significant differences of the incidences of malignant tumors between AIDS patients and general population, but the tumor types are different. The most common malignant tumors in this region are NHL and cervical cancer, which should be noted that HIV screening among patients with such tumors is conducive to comprehensive treatment to improve the efficacy.

Objective:To evaluate the occurrence of nocturnal hypotension (NHP) in nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A evidence-based medicine study. Chinese and English as search terms for NAION and NHP was used to search literature in PubMed of National Library of Medicine, Embase, Web of science, Cochrane Library, Clinical Trials, Wanfang, and China National Knowledge Infrastructure and China Biology Medicine disc. Incomplete or irrelevant literature and review literature were excluded. The literature was meta-analyzed using Review Manager 5.4 and STATA 15.0. The 95% confidence interval ( CI) were selected as the estimated value of effect size, the occurrence of NHP in NAION was calculated, and sensitivity analysis and publication bias analysis were also performed to assess the robustness of pooled outcomes. Results:According to the search strategy, 159 articles were initially retrieved, and 8 articles were finally included for meta-analysis, three prospective studies and five retrospective studies. The occurrence of NHP in NAION was 43% (95% CI, 0.36-0.50). Sensitivity analyses confirmed that the evidence was robust. Subgroup analyses showed that the occurrence of NHP in NAION nearly the same in White patients (47%, 95% CI 0.39-0.55) and Chinese patients (41%, 95% CI 0.32-0.51). The occurrence of NHP in NAION was higher in using night mean artery pressure (45%, 95% CI 0.31-0.60) as the diagnostic criteria than using night systolic blood pressure & night diastolic blood pressure (40%, 95% CI 0.32-0.50). Conclusions:The occurrence of NHP in NAION was 43%; the occurrence was similar in patients of different ethnicities. The diagnosis rate could be improved by using nMAP < 70 mm Hg (1 mm Hg=0.133 kPa) as a diagnostic criterion for NHP. Careful intervention should be taken for the blood pressure of patients with NAION and NHP.

Objective:To observe the clinical, radiographic features and prognosis of aquaporin-4 antibody positive pediatric optic neuritis (AQP4-PON).Methods:A retrospective case series. Twenty-three eyes of 14 children with AQP4-PON who were clinically confirmed in the Department of Ophthalmology of the First Medical Center of the Chinese PLA General Hospital from January 2015 to December 2018 were included in the study. All patients underwent BCVA, fundus color photography, and magnetic resonance imaging (MRI). OCT was performed on 15 eyes of 10 patients, and the peripapillary retinal nerve fiber layers (pRNFL), macular ganglion cell-inner plexiform layers (mGCIPL) thickness of the affected eyes were measured. Cell-based indirect fluorescent immunoassay was used to detect serum AQP4 antibodies and myelin oligodendrocyte glycoprotein antibodies. The follow-up time ranged from 28 to 59 months. The clinical, neuroimaging characteristics and prognosis of the children were analyzed.Results:Among 14 children, 2 were male (14.3%) and 12 were female(85.7%). The mean age of onset was 13.3±3.0 years. On the first visit, there were 10 unilateral patients and 4 bilateral patients. The first manifestations were 11 patients of optic neuritis (78.6%), 2 patients of posterior pole syndrome (14.3%), and 1 patient of myelitis (7.1%). There were 10 patients (71.4%) with eye pain, and 5 patients(35.7%) combined with autoantibodies positive. When the first onset time was less than 2 weeks, fundus examination revealed disc edema in 7 eyes (38.9%). After 3 months, the average pRNFL and mGCIPL thickness of 15 eyes underwent OCT examination were 62.33±11.07 and 54.17±5.42 μm, respectively. Orbital MRI showed that the optic nerve showed a long T2 signal in 14 patients (100.0%) and 11 patients (78.6%) with T1 intensive lesions. When the first onset was less than 2 weeks, 16 eyes (88.9%) had BCVA≤0.1, and 7 eyes(38.9%) had BCVA≤0.1 and 9 eyes (50.0%) with BCVA≥0.5 after glucocorticoid treatment. Recurrence occurred in 11 patients during follow-up and was treated with immunosuppressive agents. At the last visit, in 14 patients, 9 eyes (64.3%) were involved in both eyes, and 5 patients (35.7%) progressed to neuromyelitis optica; in 23 eyes, 8 eyes (34.8%) had BCVA≥0.5.Conclusions:AQP4-PON patients are more common in women, severely impaired visual function, easy to relapse, and some patients will progress to neuromyelitis optica.

Objective:To investigate the clinical, laboratory and imaging evaluation, treatment and prognosis of patients with idiopathic hypertrophic pachymeningitis (IHP) with ophthalmic manifestations as the first symptom.Methods:A retrospective case analysis. Eight patients displaying symptoms of IHP were recruited from the Neuro-ophthalmology Department in the First Medical Center of Chinese PLA General Hospital from January 2016 to April 2019 were inculed in this study. There were 6 males and 2 females, aged from 11 to 65 years, with an average age of 48.00±19.08 years. The course of disease ranged from 30 days to 7.5 years, with an average course of 17.00±30.08 months. The age, symptoms and signs of all patients were recorded. All patients underwent ophthalmic examination, orbit or brain MRI or CT examinations, blood routine examination, biochemistry, tumor markers, immunity, hepatitis B, syphilis, HIV, thyroid function and other laboratory tests, and lumbar puncture was performed to measure the cerebrospinal fluid (CSF) pressure and indicators. The clinical manifestations, orbital or brain MRI imaging and laboratory examination characteristics were summarized. Treatment and prognosis were also observed.Results:In total of 8 patients, visual loss was presented in 6 patients, visual loss and diplopia were presented in 1 patient, and diplopia was presented in 1patient. Binocular involvement in 7 patients and monocular involvement in 1 patient. Other symptoms including headache and hear loss and so on. Optic disc edema in 1 eye and optic disc pallor in 6 eyes were reviewed by fundus examination. The laboratory examination showed that the angiotensin converting enzyme abnormal in 4 patients, the anti-thyroid peroxidase antibody abnormal in 3 patients and immunoantibodies positive in 3 patients. CSF measurements showed that the protein level elevated in all patients. Orbit and/or brain MRI and CT examination showed that optic nerve involvement in 6 patients, oculomotor nerve involvement in 1 patient, and cavernous sinus region involvement in 2 patients. Glucocorticoid was effective in all patients, and the visual acuity significantly improved in 4 patients, the diplopia was completely resolved in 2 patients, and the disease modifying therapy (DMT) was combined to prevent recurrence in 7 patients. No recurrence was observed in an average follow-up time of 26.63±16.55 months.Conclusions:IHP patients may be first visit an ophthalmologist due to vision loss in bilateral eyes simultaneous or sequentially. IHP patients are often associated with headache and other cranial nerve paralysis symptoms. Definitive diagnosis of IHP depends on imaging examination. Glucocorticoid treatment is effective in early phase, but it is tendency to progress and relapse, suggesting combined with DMT as early as possible.

Objective:To analyze the clinical data of 203 discharged patients with corona virus disease 2019(COVID-19), and to investigate the predictors for the severe cases.Methods:Confirmed COVID-19 cases hospitalized at Zhongnan Hospital of Wuhan University from January 1 to February 1, 2020 were consecutively enrolled, who were divided into severe group and non-severe group.The clinical data of enrolled patients were collected and the clinical manifestations, laboratory results, imaging, treatments and prognosis of patients in the two groups were analyzed. Mann-Whitney U rank sum test and chi-square test were used for statistical analysis. Results:A total of 203 discharged patients with COVID-19 were enrolled. The common clinical manifestations included fever (89.2%, 181/203), dry cough (60.1%, 122/203), chest distress (35.5%, 72/203), shortness of breath(29.1%, 59/203)and myalgia or arthralgia (26.6%, 54/203). The time from disease onset to hospital admission was 5.8 days (1.0 to 20.0 days). Among 203 enrolled patients, 107(52.7%) were divided into severe group and 96(47.3%) were non-severe group. The age in severe group was 60 years (23 to 91 years), which was significantly older than non-severe group (47 years (20 to 86 years)), the difference was statistically significant ( Z=-6.12, P<0.01). There were 63.6%(68/107) patients in severe group with at least one underlying disease, which was significantly more than non-severe group (20.8% (20/96)), the difference was statistically significant ( χ2=37.60, P<0.01). The proportions of patients with increased white blood cells, decreased lymphocytes and albumin, elevated alanine aminotransferase, aspartate aminotransferase, creatinine, lactic acid dehydrogenase, creatine kinase, fasting blood glucose, D-dimer, erythrocyte sedimentation rate, C-reactive protein, interleukin-6, and procalcitonin in severe group were all higher. On admission, 172 patients (84.7%) had bilateral patchy shadows or ground glass opacity in the lungs on chest imaging study, 20(9.9%) presented pleural effusion. Fifty-five cases (27.1%) showed progressions of lung lesions on computed tomography (CT) rescan at an average interval of five days. Among 203 patients, 123(60.6%) were given oxygen therapy upon admission, 107(52.7%) were given short-term glucocorticoid therapy, and 131(64.5%) received antiviral therapy; and 26(12.8%) died. The hospital stay was 11.0 days (1.0 to 45.0 days). Conclusions:Fever is the most common symptoms in COVID-19 patients.Elderly and patients with underlying diseases are risk factors for progression to severe cases. The elderly patients should be strengthened early monitoring, paid attention to the control of underlying diseases, and reduce the occurrence of critical diseases.