Effect of Huashi Runzao Prescription on Structure and Function of Submandibular Gland in Sjögren's Syndrome Model Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Huashi Runzao prescription （HRP） on the histopathological injury and function of submandibular gland in naive non-obese diabetic （NOD/Ltj） mouse model of Sjögren's syndrome （SS） and its regulatory effect on aquaporin 5 （AQP5） expression in submandibular gland cells. MethodThe SS model was induced in NOD/Ltj mice. The NOD/Ltj female mice aged nine weeks were selected and randomly assigned into model group，HRP group （7.15 g·kg-1·d-1），and hydroxychloroquine （HCQ） group （1.30 g·kg-1·d-1）， and female BALB/c mice in the same age were selected and assigned into the normal group， with six mice in each group. Drug intervention lasted eight weeks. The water consumption and salivary flow rate （SFR） of each group were recorded. The pathological staining results of the submandibular gland of mice in each group were observed and scored. AQP5 expression was determined by immunohistochemistry （IHC） and Western blot. ResultCompared with the normal group， the model group showed increased water consumption （P<0.05） and reduced SFR （P<0.05）. Compared with the model group， the HRP group showed decreased water consumption （P<0.05） and increased SFR （P<0.05）， and the HCQ group showed increased SFR （P<0.05）. In terms of histopathological results of the submandibular gland，compared with the normal group，the model group showed increased pathological score， number of lymphocyte infiltration foci，and percentage of lymphatic infiltration area （P<0.05）. Compared with the model group， the HRP group showed reduced pathological scores and number of lymphocyte infiltration foci （P<0.05）， and the HRP group and the HCQ group showed reduced percentage of lymphatic infiltration area（P<0.05）. The results of IHC and Western blot showed that compared with the normal group，the model group showed down-regulated expression level of AQP5 protein （P<0.05）， and compared with the model group and the HCQ group，the HRP group showed up-regulated expression level of AQP5 protein （P<0.05）. ConclusionHRP can improve the secretion function of submandibular gland acinous cells and glandular structure injury in SS model mice， and its mechanism may be related to the up-regulation of AQP5 protein expression level in submandibular gland cells.

Guiqi Baizhu Prescription Combined with Oxaliplatin Protects Intestinal Barrier of Tumor-bearing Mice with Gastric Cancer by Regulation of VIP/cAMP/PKA/AQP Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Guiqi Baizhu prescription combined with oxaliplatin on the intestinal barrier of tumor-bearing mice with gastric cancer by regulating downstream aquaporin 3 （AQP3） and aquaporin 4 （AQP4） through the vasoactive intestinal peptide （VIP）/cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA） signaling pathway. MethodThe gastric cancer cell lines MFC with a density of 1×107/mL were prepared into cell suspension. The tumor-bearing mouse model of gastric cancer was established by inoculating 0.2 mL cell suspension under the right axilla of mice. After successful modeling， mice were randomly divided into 5 groups， namely， model group， oxaliplatin group （10 mg·kg-1）， and high， medium， and low-dose oxaliplatin + Guiqi Baizhu prescription groups （17.68， 8.84， 4.42 g·kg-1）， with 10 mice in each group， and the remaining 10 mice were set as a blank group. Mice in each group were treated with Chinese medicine， oxaliplatin， or normal saline by gavage or intraperitoneal injection for 14 d. The next day after the last dose， blood was taken from the eyeball to separate serum and take colonic samples. Hematoxylin-eosin （HE） staining was used to observe the changes in tissue morphology. The content of D-lactate acid （D-LA） and diamine oxidase （DAO） in the serum was determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of VIP， cAMP， PKA， AQP3， and AQP4 were detected by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the blank group， the model group showed edema in the colonic submucosa， disordered arrangement of intestinal glands in the mucosal layer， loss of goblet cells， infiltration of inflammatory cells， and villus shedding. However， there were different degrees of improvement in each administration group. As compared with the blank group， the serum levels of DAO and D-LA in the model group were significantly increased （P<0.01）. As compared with the model group， the levels of DAO and D-LA in the high-dose oxaliplatin + Guiqi Baizhu prescription group and the level of D-LA in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were decreased （P<0.05， P<0.01）. As compared with the oxaliplatin group， the levels of D-LA in the high and medium-dose oxaliplatin + Guiqi Baizhu prescription groups were decreased （P<0.05）， and the levels of DAO and D-LA in other administration groups were decreased as well， but the difference had no statistical significance. As compared with the blank group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in the model group were significantly decreased （P<0.05， P<0.01）. As compared with the model group， the mRNA and protein expression levels of VIP， cAMP， PKA， AQP3， and AQP4 in each administration group were increased， and those in the high-dose oxaliplatin + Guiqi Baizhu prescription group were significantly increased （P<0.05， P<0.01）， while the protein expression level of cAMP in the medium-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）. As compared with the oxaliplatin group， the protein expression levels of cAMP in the high-dose oxaliplatin + Guiqi Baizhu prescription group were increased （P<0.05）， and the mRNA and protein expressions of these indexes in the other groups were also increased but the differences were not statistically significant. ConclusionGuiqi Baizhu prescription combined with oxaliplatin can regulate AQP3 and AQP4 through the VIP/cAMP/PKA signaling pathway to protect the intestinal barrier of tumor-bearing mice with gastric cancer.

Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1 / 中国天然药物

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine / 中国中药杂志

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Role of Aquaporins in Heart Failure from Theory of Cardiac and Renal Coordination / 中国实验方剂学杂志

Heart failure refers to a group of clinical syndromes caused by structural or functional abnormalities of the heart that lead to impaired ejection or filling of the ventricles. The traditional Chinese medicine （TCM） theory of cardiac and renal coordination holds that the kidney governs water and plays a key role in maintaining the balance of fluid metabolism. Therefore， the treatment of water retention in heart failure can start from the heart and kidney. The basic pathogenesis of heart failure is kidney deficiency， blood stasis， and water stagnation， and the therapies including dredging the heart and kidneys， warming yang and excreting water， tonifying kidneys and activating blood， and dredging meridians and collaterals. Aquaporins （AQPs）， the key molecular basis of water metabolism， are involved in the pathogenesis of water retention in heart failure together with the arginine vasopressin system （AVP）， renin-angiotensin-aldosterone system （RAAS）， and diuretic resistance. Studies have shown that herbal medicines that regulate the heart and kidney can alleviate water retention in heart failure by targeting AQPs， thereby delaying or even reversing the progression of heart failure. This paper expounds the TCM name and pathogenesis of heart failure from the theory of cardiac and renal coordination， the role of AQPs in the pathogenesis of water retention in heart failure， and the modern connotation of the therapy of tonifying heart and kidney for heart failure， aiming to provide ideas for the prevention and treatment of water retention in heart failure by TCM.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents / Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Analysis on Changes of Aquaporin and Intestinal Flora in a Rat Model with Spleen-Yin Deficiency Syndrome / 中国实验方剂学杂志

ObjectiveTo investigate the effects of spleen-Yin deficiency on gastrointestinal absorption， water metabolism and intestinal flora in rats with spleen-Yin deficiency syndrome. MethodA rat model of spleen-Yin deficiency syndrome was established by using the composite factors， including irregular meat and vegetable diet， weight-bearing fatigue swimming and gavage with warm-heat injury-Yin drugs. The changes of body weight， food intake， water intake and duration of swimming in the blank and model groups were observed. Hematoxylin-eosin（HE） staining was used to observe the histopathological damage of the stomach and colon. Urinary excretion rate of D-xylose was determined by phloroglucinol method. The content of gastrin（GAS） in serum was determined by enzyme-linked immunosorbent assay（ELISA）. The relative expression levels of vasoactive intestinal peptide（VIP）， aquaporin 3（AQP3） and AQP4 in gastric tissues were detected by Western blot. The relative mRNA expression levels of VIP， AQP3 and AQP4 in gastric tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the changes of intestinal flora were analyzed by 16S rDNA sequencing. ResultCompared with the blank group， the results of general physical signs showed that the body weight and food intake of rats in the model group were significantly decreased， the water intake was significantly increased（P<0.05， P<0.01）， and the duration of swimming was significantly decreased（P<0.01）. Pathological examination results showed that in the mucosa of gastric tissues of rats in the model group appeared to be misaligned， the mucosa of colonic tissues could be seen to be obviously thinned or mutilated， and the epithelial cells appeared to be necrotic or even exfoliated. Compared with the blank group， the urinary D-xylose excretion rate of rats in the model group was significantly decreased（P<0.01）， and the serum GAS content was significantly decreased（P<0.05）. Compared with the blank group， Western blot results showed that the relative expression level of VIP protein in gastric tissues of rats in the model group was significantly decreased， while the relative expression levels of AQP4 and AQP3 proteins were significantly increased（P<0.01）. Compared with the blank group， Real-time PCR results showed that the relative expression level of VIP mRNA in gastric tissues of rats in the model group was significantly decreased（P<0.01）， and the relative mRNA expression levels of AQP3 and AQP4 were significantly increased（P<0.05， P<0.01）. Compared with the blank group， the results of intestinal flora analysis showed that the number of operational taxonomic units（OTUs） and α-diversity increased and β-diversity decreased significantly in the model group， the abundance of Porphyromonadaceae was increased significantly， and the abundance of Oscillibacter_ruminantium was decreased significantly（P<0.05）. Spearman correlation analysis showed that Porphyromonadaceae was significantly positively correlated with AQP4 protein level， while Oscillibacter_ruminantium was significantly positively correlated with VIP protein level， and negatively correlated with AQP3 and AQP4 protein levels（P<0.05）. Linear discriminant analysis effect size（LEfSe） analysis results showed that there were significant differences in a variety of intestinal bacteria between groups， and the intestinal bacteria of the model group were significantly enriched in the phylum/order/family/genus of Elusimicrobia， Betaproteobacteria， Burkholderiales， Sutterellaceae and Parasutterella（P<0.05）. ConclusionSpleen-Yin deficiency syndrome can weaken the digestion and absorption capacity of gastrointestinal tract， and cause the disturbance of water metabolism and intestinal flora. AQP4， AQP3 and VIP protein levels of gastric mucosa are closely related to Porphyromonadaceae and Oscillibacter_ruminantium. And AQP4， AQP3 and VIP may be involved in the regulation of intestinal flora in order to affect the physiological function of spleen governing transportation and transformation.

Therapeutic Effect and Mechanism of Yiqi Huoxue Tongbian Prescription on Slow Transit Constipation in Rats / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Yiqi Huoxue Tongbian prescription on slow transit constipation （STC） in rats. MethodThe rat model of STC was established by gavage of loperamide hydrochloride. Rats were assigned into control， model， mosapride， low-， medium-， and high-dose （3.51， 7.02， and 14.04 g·kg-1， respectively） Yiqi Huoxue Tongbian prescription groups. The changes of general signs， fecal moisture content， and intestinal propulsion rate were measured after model establishment and drug administration. The colonic mucosal changes were observed by hematoxylin eosin staining. Enzyme-linked immunosorbent assay was employed to determine the content of substance P （SP） and vasoactive intestinal peptide （VIP） in the colon of rats in each group. The gray values of aquaporin （AQP） 3， AQP4， AQP8， and c-Kit in rat colon tissue were measured by immunohistochemistry and Western blot， and the changes of intestinal flora were detected by 16S rRNA high-throughput sequencing. ResultCompared with the model group， 10 days of treatment with Yiqi Huoxue Tongbian prescription increased the fecal moisture content and intestinal propulsion rate （P<0.01）. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups and the mosapride group showed no obvious mucosal inflammation and neat arrangement of goblet cells with a large number in the colon tissue. Moreover， the three groups showed increased SP content （P<0.01） and decreased VIP content （P<0.01） in the serum. The medium- and high-dose Yiqi Huoxue Tongbian prescription groups showed down-regulated protein levels of AQP3， AQP4， and AQP8 （P<0.01） and up-regulated protein level of c-Kit （P<0.01）. The drug administration groups presented slightly increased observed species， Chao1， ACE， and Shannon， Simpson， and PD whole tree. The principal component analysis showed that the control group had a short distance with the high- and medium-dose Yiqi Huoxue Tongbian prescription groups， indicating that high- and medium-dose Yiqi Huoxue Tongbian prescription can recover the intestinal flora to that in the control group. ConclusionYiqi Huoxue Tongbian prescription can alleviate the defecation status of rats with slow transit constipation by down-regulating the expression of AQP3， AQP4， and AQP8 to reduce the absorption of water in the intestine， up-regulating the expression of c-Kit to increase the number and distribution of Cajal interstitial cells， and regulating the balance of flora in the colon tissue.

Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex Combination Alleviates Slow Transit Constipation due to Yang Deficiency in Rats via Regulating VIP/cAMP/PKA/AQP Pathway in Colon / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex in regulating the intestinal function in the rat model of slow transit constipation （STC） due to yang deficiency via the vasoactive intestinal peptide （VIP）/cathelicidin antimicrobial peptide （cAMP）/protein kinase A （PKA）/aquaporin （AQP） pathway. MethodSD rats were randomized into 6 groups （n=6）， including a control group， a model group， high-， medium-， and low-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex groups， and a prucalopride group. Other groups except the control group were treated with loperamide hydrochloride combined with ice water by gavage for the modeling of STC due to yang deficiency. The number of fecal pellets， time to the first black stool defecation， fecal water content， intestinal propulsion rate， and score of fecal properties were recorded in each group. At the end of the treatment， the colon was stained with hematoxylin-eosin （HE） to reveal the histopathological changes and Alcian blue/periodic acid-Schiff （AB-PAS） to reveal the secretion of colonic mucus. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the level of VIP in the serum. The mRNA level of AQP in the colon was measured by polymerase chain reaction （Real-time PCR）. Immunohistochemical staining was performed to observe the expression of AQPs in the colon and kidney tissues. Western blot was performed to determine the protein levels of cAMP， PKA， and VIP in the colon tissue. ResultCompared with the control group, the model group had longer time to the first black stool defecation, reduced fecal pellets and water content, reduced Bristol Stool Form Scale score and intestinal propulsion rate, and constipation aggravated（P<0.01）. Moreover, increased the intestinal lesions, reduced the mucus secretion, reduce the serum VIP level, up-regulated the expression levels of AQP1 in the colon and kidney tissues, inhibited the expression of AQP3 and AQP9（P<0.01）., and down-regulated the protein levels of cAMP, PKA, and VIP in the colon tissue. Compared with the model group， the high-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex group had shortened time to the first black stool defecation， increased fecal pellets and water content， increased Bristol Stool Form Scale score and intestinal propulsion rate， and alleviated constipation symptoms. Moreover， high-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex reduced the intestinal lesions， increased the mucus secretion， elevated the serum VIP level（P<0.01）.， down-regulated the expression levels of AQP1 in the colon and kidney tissues， promoted the expression of AQP3 and AQP9（P<0.05，P<0.01）， and up-regulated the protein levels of cAMP， PKA， and VIP in the colon tissue. The medium- and low-dose groups had weaker effect than the high-dose group（P<0.01）. ConclusionHigh-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex can improve the intestinal motility and balance the intestinal water and fluid metabolism by up-regulating the VIP/cAMP/PKA/AQP pathway， thereby mitigating the constipation symptoms in the rat model of slow transit constipation due to yang deficiency.

Pathogenesis of aquaporin-4 immunoglobulin G positive neuromyelitis optica spectrum disorder / 中华神经科杂志

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system characterized by the involvement of the optic nerve and spinal cord. The main clinical features are optic neuritis, acute myelitis, and area postrema syndrome. Aquaporin-4 (AQP4)-IgG-positive patients accounted for the majority and compared with AQP4-IgG-negative patients, the clinical symptoms were more severe, the recurrence was more frequent, and the disability rate was higher. The pathogenesis of AQP4-IgG-positive NMOSD is still not clear. This article reviews the research progress of the pathogenesis of AQP4-IgG-positive NMOSD.

Comparative study on radiological features between serum aquaporin 4 antibody positive and negative neuromyelitis optica spectrum disorder / 中华放射学杂志

Objective:To investigate the clinical and imaging differences between serum aquaporin 4 (AQP4) antibody positive and negative patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data and radiologic findings of 89 NMOSD patients diagnosed at Beijing Tiantan Hospital, Capital Medical University from January 2018 to June 2022 were retrospectively analyzed. There were 17 male cases and 72 female cases, aged 18-74 years. According to the results of serum AQP4 antibody test, the patients were divided into AQP4 antibody positive group and AQP4 antibody negative group, and the differences in clinical data, lesion distribution, lesion characteristics, and brain area volume between the 2 groups were compared using independent sample t-test and χ 2 test, and the correlation between brain area volume and expanded disability status scale (EDSS) scores was further investigated using Spearman correlation analysis. Results:There were 68 cases in the AQP4 antibody positive group and 21 cases in the AQP4 antibody negative group. Patients in both groups were predominantly female, but the percentage of females in the AQP4 antibody-positive group (86.8%, 59/68) was higher than that in the AQP4 antibody-negative group (61.9%, 13/21), with a statistically significant difference (χ 2=4.91, P=0.027). The incidence of optic neuritis in AQP4 antibody negative group (66.7%, 14/21) was higher than that in antibody positive group (41.2%, 28/68), with a statistically significant difference (χ 2=4.18, P=0.041). In the distribution of intracranial lesions on MRI, the probability of lesions involving the brain stem in AQP4 antibody negative group (47.6%, 10/21) was higher than that in AQP4 antibody positive group (23.5%, 16/68), the difference had statistically significance (χ 2=4.50, P=0.034). The volumes of whole brain white matter, right amygdala, right accumbens-area and right ventral diencephalon in AQP4 antibody positive group were lower than those in AQP4 antibody negative group ( P<0.05), and the volumes of the right accumbens-area were negatively correlated with the EDSS scores in AQP4 antibody positive group ( r=-0.628, P=0.009). Conclusion:There are differences in clinical and imaging manifestations between AQP4 antibody positive and AQP4 antibody negative patients, which provides more basis for clinical in-depth understanding of NMOSD.

Congenital renal diabetes insipidus caused by aquaporin 2 gene mutation in siblings: 2 cases report and literature review / 中国综合临床

Objective:To improve clinicians' understanding of congenital nephrogenital diabetes insipidus (CNDI) and to reduce missed and misdiagnosis. Methords 　Based on the literature, the clinical data and gene mutation of 2 patients with CNDI who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Henan University of Science and Technology on July 30, 2020 were analyzed retrospectively. Results:(1) The presentee, 4 years old, had irritable thirst, polydipsia and polyuria for more than 3 years. The sister, 2.5 years old, had irritable thirst, polydipsia and polyuria for more than 2 years. The clinical diagnosis was “CNDI”, and the symptoms improved after treatment with hydrochlorothiazide. (2) The genetic test revealed that the congenital nephrogenic uremia and her sister had a heterozygous mutation of c.170A>C (p.Q57P) and c.211G>A (p.Vl71M) in the aquaporin-2 gene, and the mother carried the AQP2 gene. c.170A>C(p.Q57P) mutation.Conclusion:CNDI is a rare disease. Early diagnosis and treatment can improve the prognosis of patients to the greatest extent, and prenatal diagnosis can guide eugenics.

Optic neuromyelitis in relation with juvenile idiopathic arthritis: A case report

Optic neuromyelitis (ONM), also called neuromyelitis optica spectrum (Neuromyelitis Optica Spectrum Disorders, NMOSD) is recognized as an inflammatory autoimmune demyelinating disease of the central nervous system, mediated by autoantibodies against the aquaporin-4 receptor (AQP4-IgG). It predominantly affects the optic nerves and the spinal cord.1-3 It is known that patients with immune disorders are more likely to present other autoimmune diseases, but the relation between juvenile idiopathic arthritis and ONM has not been completely described.5 In this paper, we report a case of a patient with juvenile idiopathic arthritis, presenting with a rapidly progressive neurological condition, who is treated with biological drugs.1-4

La neuromielitis óptica (NMO), también llamada espectro de la neuromielitis óptica (neuromyelitis optica spectrum disorders) se reconoce como una enfermedad inflamatoria, autoinmune, desmielinizante del sistema nervioso central, mediada por autoanticuerpos contra el receptor de acuaporina 4 (AQP4-IgG) que afecta predominantemente a los nervios ópticos y la médula espinal1-3. Es conocido que los pacientes con trastornos inmunitarios tienen más probabilidades de presentar otras enfermedades autoinmunes; sin embargo, no está completamente descrita la asociación entre artritis idiopática juvenil y NMO5. En este escrito se reporta el caso de una paciente que cursa con artritis idiopática juvenil, inició con compromiso neurológico rápidamente progresivo, y es tratada con medicamentos biológicos1-4.

Relationship with Nephrotoxicity of Abemaciclib in Rats: Protective Effect of Curcumin

Abemaciclib (ABE) has been reported to cause gastrointestinal toxicity. Therefore, it is important to investigate the question of whether abemaciclib administration causes nephrotoxicity in the gastrointestinal tract, and if so, what pathophysiological pathways it follows. In this study, the relationship between ABE administration and nephrotoxicity and the protective effect of Curcumin (CMN) was investigated. Forty female rats were equally divided into the sham, dimethyl sulfoxide (DMSO), CMN, abemaciclib and ABE+CMN groups. Aquaporin (AQP) 1-7, TNF-?, IL-1?, intercellular adhesion molecule (ICAM)-1, IL-10 and IL-37 levels in serum and kidney tissue homogenates were measured by ELISA. In addition, Urea and Creatinine were measured in serum samples. Furthermore, histopathological examination was performed in kidney tissues and Bax, Caspase-3 and Bcl-2 expression levels were determined immunohistochemically. The levels of AQP1-7 and IL-10 in the ABE group were partially lower than in the other groups, while the ratio of TNF?, IL-1?, MDA, caspase-3 and Bax/Bcl2 were high. In addition, kidney tissue was examined histopathologically. However, AQP1 and 7 levels in the ABE+CMN group were higher than in the ABE group, while TNF-?, IL-1?, MDA, Caspase-3 levels and Bax/Bcl2 ratio were low. In addition, the poor histopathological changes in the ABE group were largely restored in the ABE+CMN. The data presented that ABE in rats can adversely affect functions and histology of kidneys through the increase in oxidative stress, pro-inflammatory cytokines and apoptosis, but CMN therapy may be protective against the nephrotoxic effects of ABE

Aquaporin-4 protein antibody-associated optic neuritis related to neuroendocrine tumor after receiving an inactive COVID-19 vaccine

Neuromyelitis optica (NMO), also known as Devic’s disease, is a rare, autoimmune, and recurrent demyelinating disorder that primarily affects the spinal cord and optic nerve. We report a case with recurrent optic neuritis caused by the paraneoplastic NMO spectrum disorder in the setting of a gastric neuroendocrine tumor 2 weeks after receiving an inactive COVID?19 vaccine.

Clinico-epidemiologic characteristics of optic neuritis in a tertiary eye centre in Eastern India based on the status of serum aquaporin-4 antibody

Purpose: To elucidate the clinico?epidemiologic characteristics of optic neuritis based on the status of serum aquaporin?4 antibody (AQP4?Ab) in patients with optic neuritis (ON). Methods: Medical records of 106 patients with ON and a follow?up of 3 years were reviewed. For each patient, the following data were extracted: medical history, findings of the ocular examination, brain, orbital or spinal MRI, and serological tests for AQP4. The ON was classified as typical or atypical based on disc examination and improvement in vision after intravenous methylprednisolone (IVMP). The clinical findings (typical or atypical), disease course, and outcomes were analyzed according to the serostatus of the ON. Results: 10 patients ((9.4%) were seropositive for AQP4?Ab; all had atypical ON. 96 patients (91%) were seronegative for AQP4?Ab: 36 atypical ON and 60 typical ON. Profound visual impairment at presentation was seen in all patients. However, at the end of the study period, seropositive and seronegative atypical ON had poor visual outcomes as compared to seronegative typical ON (P = 0.002). Five seropositive and four seronegative patients with atypical ON developed transverse myelitis. Bilateral disease with relapse was more in seropositive patients (80%); however, seronegative with atypical ON also had bilateral presentation and relapse in 42% and 41%, respectively. Conclusion: AQP4?Ab seropositive patients mostly present with atypical features such as bilateral recurrent ON, poor visual outcome, and increased incidence of transverse myelitis. However, atypical clinical features can also be seen in seronegative ON with a poor visual outcome and a recalcitrant course.

A case of AQP4-IgG-negative neuromyelitis optica spectrum disorders with initial clinical manifestation of painful trigeminal neuropathy and literature review / 中国医师杂志

Objective:To explore the clinical manifestations and imaging of neuromyelitis optica spectrum disorders (NMOSD) with negative aquaporin-4 immunoglobulin G antibody (AQP4-IgG) with initial clinical manifestation of painful trigeminal neuropathy.Methods:The symptoms, signs, imaging examinations, diagnosis and treatment of a case of AQP4-IgG-negative NMOSD in neurology department of Affiliated Hospital of Southwest Medical University were reported and the relevant literatures were reviewed.Results:In the first episode, the patient started with right-sided facial pain with segmental paresthesia in the left limb. And In the second episode, the patient started with intractable hiccups and vomiting with weakness and paresthesia in the left limb. Magnetic resonance imaging of the skull and spinal cord revealed that the lesion involved the medulla oblongata and cervical medulla. AQP4 antibody, myelin oligodendrocytes glycoprotein (MOG) antibody, myelin basic protein (MBP) antibody and oligoclonal bands(OCB) of serum and cerebrospinal fluid were negative. The clinical diagnosis was AQP4-IgG-negative NMOSD. After treatments with hormonal anti-inflammatory and analgesic therapy, the patient′s facial pain, sensory abnormalities, hiccups, vomiting and limb weakness improved significantly.Conclusions:Painful trigeminal neuropathy may be the initial clinical manifestation of AQP4-IgG-negative NMOSD. NMOSD of presenting solely with painful trigeminal neuropathy is easy to be misdiagnosed and missed. Magnetic resonance examination is helpful for the early diagnosis of NMOSD.

Glymphatic system and cerebral edema after ischemic stroke / 国际脑血管病杂志

Glymphatic system is a fluid transport and material clearance system found in recent years. It promotes the flow and exchange of cerebrospinal fluid and interstitial fluid, remove metabolic waste, and maintain the stability of the internal environment of the brain through the perivascular space and aquaporin 4 on astrocytes. Recent studies have shown that the glymphatic system plays an important role in the intake and discharge of the fluid in brain, and the changes of glymphatic system may be an important reason for brain edema after ischemic stroke. This article reviews the pathophysiological mechanism and related therapeutic targets of glymphatic system in the formation of cerebral edema after ischemic stroke, in order to provide new ideas for the treatment of cerebral edema after ischemic stroke.

Neuromyelitis optica spectrum disorders / 中华神经科杂志

Neuromyelitis optica spectrum disorders (NMOSD) is an immune mediated inflammatory demyelinating disease of the central nervous system. Optic neuritis and longitudinally extensive transverse myelitis are the main clinical signs, and the etiology is mainly related to aquaporin 4 (AQP4) antibody. AQP4 is the target antigen of immune attack. NMOSD is characterized by optic neuritis, longitudinally extended transverse myelitis, medulla area postrema syndrome, brainstem syndrome, diencephalic syndrome and cerebral syndrome. In recent years, the etiological mechanism, clinical diagnosis and monoclonal antibodies targeting new mechanisms of NMOSD have made great progress, which promoted the development of clinical neurology.

Relapse risk analysis in anti-aquaporin 4-IgG positive neuromyelitis optica spectrum disorders patients treated with immunosuppressant / 中华神经科杂志

Objective:To investigate the relapse risk factors of anti-aquaporin 4 (AQP4)-IgG positive neuromyelitis optica spectrum disorders (NMOSD) patients treated with immunosuppressant.Methods:Data (from January 2011 to June 2021) of AQP4-IgG positive NMOSD patients treated with immunosuppressant for longer than 5 years from MSNMObase, a hospital-based electronic registry for multiple sclerosis and related disorders in Peking Union Medical College Hospital, were collected. Clinical features and risk factor differences between patients with and without relapse under the immunosuppressive therapy were analyzed.Results:One hundred and twelve patients with AQP4-IgG positive NMOSD were included, 105 (93.8%) of which were female. The disease onset age was (34.9±11.3) years, 13(11.6%) had an older disease onset age than 50 years (late onset), and the disease duration was 8.1 (6.6, 11.4) years. Sixty-four (57.1%) patients had relapse, and the proportion of late onset patients was significantly lower in relapse group than in non-relapse group [4/64(6.3%) vs 9/48(18.8%), χ2=4.18, P=0.041]. Compared with those without relapse, both the annualized relapse rate (ARR) before treatment [1.07 (0.36, 2.25) vs 0.34 (0, 1.11), Z=2.92, P=0.003] and the proportion of patients with relapse before treatment [54/64(84.4%) vs 33/48(68.8%), χ2=3.86, P=0.049] were significantly higher for patients in relapse group. Multivariate Logistic regression analysis revealed the relapse risk of late-onset patients was lower than that of early-onset patients ( HR=0.26, 95% CI 0.10-0.73, P=0.010) and patients with higher ARR before treatment showed a higher risk of relapse under the immunosuppressive therapy ( HR=1.55,95% CI 1.26-1.91, P<0.001). Conclusion:AQP4-IgG positive NMOSD patients with younger disease onset age than 50 years or with frequent relapses before treatment had a higher relapse risk under the immunosuppressive therapy, and they may need highly effective treatments.