目的:评价氯喹那多普罗雌烯阴道片对产后阴道黏膜修复及防治生殖道感染的作用。方法:对212例产后6～8周复诊患者随机分为实验组92例和对照组120例。实验组给予氯喹那多普罗雌烯阴道片阴道上药,每日一片共18日;对照组仅给予温盐水清洁阴部。治疗前后检查两组的阴道分泌物情况。结果:用药前实验组与对照组比较生殖道状况均无统计学差异(Pgt;005)。用药后实验组生殖道状况正常为80%,而对照组正常仅为36%,两组比较差异有显著性(Plt;005)。实验组生殖道感染12例,无真菌和滴虫感染,均为非特异性阴道炎,患病率1304%,有效率8695%。对照组生殖道感染84例,有效率3000%,患病高低顺序依次为非特异性阴道炎4167%,真菌性阴道炎2083%,滴虫性阴道炎 750%。结论:氯喹那多普罗雌烯阴道片能有效治疗生殖道非特异性炎症,真菌性、滴虫性阴道炎,促进产后的阴道黏膜修复,防治产后生殖道感染。
ObjectiveTo observe the efficacy of low-dose methylprednisolone combined with hydroxychloroquine and methotrexate in the treatment of rheumatoid arthritis (RA). MethodsBetween January 2011 and May 2013, 60 RA patients on their first treatment with a disease course of less than or equal to 2 years were randomly divided to control group and treatment group Ⅰ with 30 patients in each. Patients in both the two groups were given hydroxychloroquine and methotrexate therapy, while the control group was treated with meloxicam (7.5 mg/time, 2 times/d) in addition, and the treatment group one was given methylprednisolone (4 mg/time, 2 times/d) in addition. Another 30 RA patients with a disease course of more than 5 years with no standardized treatment were designated into the treatment group Ⅱ. They accepted the same treatment scheme as treatment group Ⅰ. All the patients were evaluated one week after treatment to assess their clinical symptoms. Twelve weeks before and after treatment, the patients were evaluated on their clinical indicators and immunological indicators. ResultsThe clinical symptoms of patients in treatment group Ⅰ and Ⅱ were rapidly relieved within one week after treatment, and the curative effect was significantly higher than that in the control group (P<0.05). Twelve weeks after treatment, the treatment groups were significantly improved compared with the control group in clinical symptoms and DSA28 (P<0.05). The improvement of clinical symptoms and immunological tests in treatment group Ⅰ was more obvious than that in treatment groupⅡ. ConclusionLow-dose methylprednisolone combined with hydroxyl chloroquine and methotrexate can quickly and effectively relieve the clinical symptoms of the patients with RA, and patients with a shorter course of the disease have better clinical efficacy.
ObjectivesTo systematically review the efficacy and safety of hydroxychloroquine (HCQ) and chloroquine (CQ) for oral lichen planus (OLP).MethodsPubMed, The Cochrane Library, Web of Science, CNKI, CBM, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) of HCQ and CQ for OLP from inception to September, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 10 RCTs involving 726 patients were included. The results of meta-analysis showed that: HCQ or CQ were more effective than placebos (P<0.05). Nevertheless, they were inferior to oral traditional Chinese medicine (RR=0.75, 95%CI 0.69 to 0.82, P<0.000 01). In addition, the ratio of CD4+/CD8+ T cell increased significantly in peripheral blood of OLP patients after treatment with HCQ or CQ (MD=–0.28, 95%CI –0.44 to –0.13, P=0.000 3). The incidences of adverse reaction of HCQ or CQ were higher than orally traditional Chinese medicine (RR=11.80, 95%CI 4.85 to 28.68, P<0.000 01), and the difference was statistically significant.ConclusionsCurrent evidence shows that the efficacy of HCQ or CQ for OLP were significantly superior to placebo, while inferior to orally traditional Chinese medicine. The possible therapeutic mechanism of HCQ or CQ for OLP may be related to the regulation of the ratio of CD4+/CD8+ T cells and cellular immunity of OLP patients. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusion.
ObjectiveTo investigate the protective effects of different concentrations of chloroquine on RGC in n-methyl-d-aspartate (NMDA) injured mice and its possible mechanisms.MethodsFifty-four healthy male C57/BL6 mice were randomly divided into three groups, 18 in each group. The mice in low-dose chloroquine group were intraperitoneally injected with chloroquine solution at a dose of 10 mg/kg daily. Mice in high-dose chloroquine group were intraperitoneally injected with chloroquine solution at a dose of 100 mg/kg, and the mice in control group were intraperitoneally injected with the same volume of PBS. NMDA intravitreal injection was performed 2 days after intraperitoneal injection, 5 nmoles NMDA was injected into the left eye, and the same volume of PBS was injected into the right eye as a control. The RGC staining of retinal plaques were performed 7 days after NMDA injection, and the number of alive RGC was calculated. The visual acuity and electroretinogram were used to evaluate the electrophysiological functions of RGC at 9 and 10 days after modeling. Real-time quantitative PCR and retinal frozen sections and glial fibrillary acidic protein (GFAP) immunofluorescence staining were performed 11 days after NMDA injection to evaluate the glial activation of the retina. The density, visual acuity, and the amplitude of PhNR-wave of RGC between groups were compared by one-way analysis of variance.ResultsAt 7 days after NMDA injection, the density of RGC in retinal patch of low-dose chloroquine group was significantly higher than that of intraperitoneal injection of PBS control group (F=54.41, P＜0.01). The density of RGC in retinal patch of high-dose chloroquine group was lower than that of control group (F=1.18, P＞0.05). The visual acuity was higher than control group, and the difference was statistically significant (F=9.10, P＜0.05). The amplitude of PhNR-wave was significantly higher in low-dose chloroquine group than that of the control group (F=17.60, P＜0.01). The mRNA level of inflammatory factor and GFAP positive signal was also significantly lower than that of the control group (F=23.66, P＜0.05). The amplitude of PhNR-wave, the expression of GFAP (F=110.20, P＜0.01) and the mRNA level of inflammatory factors (F=167.60, 17.78; P＜0.01) in the high-dose chloroquine group were higher than the other two groups, and the differences were statistically significant.ConclusionsIn NMDA injury retinal model, low-dose chloroquine significantly increased the survival and physiological function of RGC, and the mechanism may be related to the inhibition of glial activation and inflammatory response. High-dose of chloroquine would aggravate the apoptosis of RGC.
Hydroxychloroquine is widely used in a variety of autoimmune diseases. However, long-term use of hydroxychloroquine can cause severe retinopathy, which has a complex pathogenic mechanism and diverse clinical manifestations, mainly manifested as photoreceptor and retinal pigment epithelial damage and irreversible vision loss. Identifying damage before retinitis pigment epithelium lesions preserve central vision, so early detection is crucial to slow disease progression and reduce vision loss. The development of multimodal imaging technology and the issuance of the latest treatment guidelines provide a powerful tool for the early screening and treatment of hydroxychloroquine retinopathy. Proficient in the latest guidelines for the treatment of hydroxychloroquine can better guide clinicians to do a good job in disease screening and management, recommend risks, safe dosages and appropriate screening procedures to patients and strengthen the prevention of hydroxychloroquine retinopathy, which will help save the vision of more patients and reduce the waste of medical resources.
ObjectiveTo evaluate whether there are changes in cone cells in patients with pre-clinical hydroxychloroquine (HCQ) retinopathy using an adaptive optics (AO) retinal camera. MethodsA retrospective case-control study. From May 2020 to July 2020, 46 patients who were treated in Department of Rheumatism and Immunology, Hainan Hospital of PLA General Hospital with rheumatic immune diseases were included. All patients had a history of HCQ use and no obvious abnormality was found in fundus examination; 105 healthy people with similar demographic characteristics without a history of hydroxychloroquine were recruited as the control group were included. All subjects received the routine ophthalmological examination including best corrected visual auity (BCVA), spectral-domain optical coherence tomography (SD-OCT), Fundus autofluorescence (FAF), visual field, endoscopy of the cornea, and the measurement of axial length (AL). The BCVA was performed with the Snellen visual acuity chart, and the result was converted to logarithmic minimum angle of resolution (logMAR) visual acuity for statistic. Among the 46 cases, 6 cases were males and 40 cases were females. Age was (42.02±13.81) years old; logMAR BCVA was 0.063±0.015; AL was (23.95±0.726) mm. Visual field, macular SD-OCT, FAF examination showed no abnormality. The average cumulative dose of HCQ was 522.60 (6-1 728) g. rtx1 AO retinal camera was used to collect fundus images of subjects in four quadrants above the retina, nasal side, lower side and temporal side with 3°centrifugation from the fovea in both eyes. The cone density, cone spacing, cone arrangement regularity and the proportion of the nearest cones with 6 (nn=6) were measured in the four quadrants. The density of cone cells between the left and right eyes in case group and control group were compared by paired t test. The density and spacing of cone cells in each quadrant were compared by t test of two independent samples. ResultsCompared with the control group, the cone cell density in the four quadrants of the left eye and the nasal, superior and inferior sides of the right eye in the case group was significantly decreased, and the difference was statistically significant (t=4.247, 2.107, 4.884, 2.254, 2.643, 4.445, 4.116; P＜0.05). The cone spacing in the nasal and temporal sides of the left eye of the patients in the case group was significantly larger than that in the control eye, with statistical significance (t=2.750, 3.318; P＜0.05). Compared with the control group, the regulatign of cone cell arrangement in the left temporal side of the right and left eye in the case group were significantly reduced, the difference was statistically significant (P=0.002, 0.011). The proportion of nn=6 in the inferior and temporal sides of the right eye decreased significantly in the case group, and the difference was statistically significant (P=0.006, 0.032). ConclusionAO retinal imaging can detect the changes of cone cells in the early clinical stage of HCQ retinopathy.
Objective To investigate the effects and mechanisms of hydroxychloroquine sulfate (HCQ) on pulmonary fibrosis through the PI3K/AKt/mTOR signalling pathway. Methods Paraquat intraperitoneal injection was used to establish a mouse model of pulmonary fibrosis. Thirty-six SPF C57BL/6J female mice were randomly divided into a blank group, a paraquat group (20 mg/kg) and a HCQ intervention group. The HCQ intervention group was divided into two subgroups (10 mg/kg and 30 mg/kg) according to different doses. The general condition and body weight changes of mice were observed. twenty-one days later, lung tissues were stained with hematoxylin-eosin and Masson’s pathological staining, and the content of inflammatory factors (IL-1β, IL-6, TNF-α) and hydroxyproline (HYP) were detected by ELISA. Alpha-smooth muscle actin (α-SMA), E-cadherin (E-cad), the expression levels of PI3K/Akt/mTOR pathway-related proteins, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKt), and mammalian target of rapamycin (mTOR) were detected by Western blot. The gene expression levels of α-SMA and E-cad were detected by q-PCR. Results Compared with the blank group, the mice in the paraquat group had lower body weight, worse general condition, higher serum levels of inflammatory factors, increased lung structure destruction and collagen deposition, significantly increased HYP content, and higher expression level of PI3K/AKt/mTOR signaling pathway related proteins (all P<0.05). The expression levels of E-cad protein and gene decreased, α-SMA protein and gene increased (all P<0.05). While the HCQ intervention group improved the degree of pulmonary fibrosis in different degrees, and the relevant indexes of PI3K/AKt/mTOR signaling pathway decreased compared with the paraquat group (all P<0.05). Conclusion HCQ can ameliorate paraquat-induced pulmonary fibrosis by inhibiting the PI3K/AKt/mTOR signaling pathway.
Hydroxychloroquine retinopathy is an ocular lesions that develops following long-term or excessive use of hydroxychloroquine. The early clinical presentation of this lesion is nonspecific and is often detected when severe central vision impairment occurs in late stage. It currently mainly includes hydroxychloroquine binding to melanin, inducing degeneration of the retinal pigment epithelium, increasing the pH of lysosomes in the retinal pigment epithelium and interfering with the visual cycle. In recent years, with the development of retinal imaging technology and the in-depth study of hydroxychloroquine retinopathy, characteristic fundus structural changes such as retinal and choroidal thickness and blood vessels may occur in the early stage. This not only provides an important basis for the early diagnosis of hydroxychloroquine retinopathy, but also provides important clues for investigating its pathogenesis. Clinicians' proficiency in relevant fundus changes and pathogenesis will facilitate early diagnosis and treatment, while also minimizing irreversible central vision impairment in patients.