Sjogren’s syndrome presenting as hypokalemic periodic paralysis, a rare manifestation: A case series

Sjogren’s syndrome is a chronic and slowly progressing autoimmune disease characterized by lyphocytic infiltration of exocrine glands resulting in Sicca syndrome (xerostomia and keratocunjuntivitis sicca). The disease can present alone or along with other autoimmune diseases leading to significant organ specific and systemic disease. Middle aged women (Female: Male: 9:1) are primarily affected. Extraglandular (systemic) manifestations are seen in one third of patients with Sjogren’s syndrome. Among the extraglandular manifestations, renal involvement is commonly seen. Renal involvement in the form of tubulointerstitial nephritis (TIN) is more common compared to glomerular involvement. Distal renal tubular acidosis (RTA) is more common manifestation of TIN presenting as mild hypokalemia, metabolic acidosis, and rarely with hypokalemic periodic paralysis. We report three cases of hypokalemic periodic paralysis with metabolic acidosis, two in respiratory paralysis, diagnosed as distal RTA. On further evaluation of distal RTA, the patient diagnosed to have Sjogren’s syndrome and managed accordingly. Our report shows that Sjogren’s syndrome is a rare but important cause of hypokaemic periodic paralysis due to RTA.

Don’t pin it all on a stereotype

Hypercalcemia is one of the most frequently encountered problems in endocrinology OPD. Although the evaluation may not always be straightforward in all scenarios. Common factors affecting calcium levels such as dehydration, improper sample collection, and vitamin D supplementation may mask a serious underlying disorder. Here, we discuss a case of an elderly female who had symptoms of myelopathy and hypercalcemia whose etiology was initially attributed to excessive sup

A chiral metal-organic framework {(HQA)(ZnCl2)(2.5H2O)}n for the enantioseparation of chiral amino acids and drugs / 药物分析学报

Chiral metal-organic frameworks(CMOFs)with enantiomeric subunits have been employed in chiral chemistry.In this study,a CMOF formed from 6-methoxyl-(8S,9R)-cinchonan-9-ol-3-carboxylic acid(HQA)and ZnCl2,{(HQA)(ZnCl2)(2.5H2O)｝n was constructed as a chiral stationary phase(CSP)via an in situ fabrication approach and used for chiral amino acid and drug analyses for the first time.The{(HQA)(ZnCl2)(2.5H2O)}n nanocrystal and the corresponding chiral stationary phase were systematically characterised using a series of analytical techniques including scanning electron microscopy,X-ray diffraction,Fourier transform infrared spectroscopy,circular dichroism,X-ray photoelectron spectros-copy,thermogravimetric analysis,and Brunauer-Emmett-Teller surface area measurements.In open-tubular capillary electrochromatography(CEC),the novel chiral column exhibited strong and broad enantioselectivity toward a variety of chiral analytes,including 19 racemic dansyl amino acids and several model chiral drugs(both acidic and basic).The chiral CEC conditions were optimised,and the enantioseparation mechanisms are discussed.This study not only introduces a new high-efficiency member of the MOF-type CSP family but also demonstrates the potential of improving the enantiose-lectivities of traditional chiral recognition reagents by fully using the inherent characteristics of porous organic frameworks.

Recent applications and chiral separation development based on stationary phases in open tubular capillary electrochromatography(2019-2022) / 药物分析学报

Capillary electrochromatography(CEC)plays a significant role in chiral separation via the double sepa-ration principle,partition coefficient difference between the two phases,and electroosmotic flow-driven separation.Given the distinct properties of the inner wall stationary phase(SP),the separation ability of each SP differs from one another.Particularly,it provides large room for promising applications of open tubular capillary electrochromatography(OT-CEC).We divided the OT-CEC SPs developed over the past four years into six types:ionic liquids,nanoparticle materials,microporous materials,biomaterials,non-nanopolymers,and others,to mainly introduce their characteristics in chiral drug separation.There also added a few classic SPs that occurred within ten years as supplements to enrich the features of each SP.Additionally,we discuss their applications in metabolomics,food,cosmetics,environment,and biology as analytes in addition to chiral drugs.OT-CEC plays an increasingly significant role in chiral separation and may promote the development of capillary electrophoresis(CE)combined with other instruments in recent years,such as CE with mass spectrometry(CE/MS)and CE with ultraviolet light detector(CE/UV).

Application progress in classification of puncture biopsy after kidney transplantation / 器官移植

Renal allograft biopsy (biopsy) remains the "gold standard" for the diagnosis of renal dysfunction after kidney transplantation. Puncture biopsy after kidney transplantation could be divided into indicative biopsy and protocol biopsy according to renal function of the patients. Indicative biopsy is mainly applied to diagnose postoperative complications of kidney transplantation, evaluate the severity of disease and guide subsequent treatment. Protocol biopsy is primarily employed to regular monitor renal allograft function of kidney transplant recipients and exclude subclinical rejection and other complications. Due to the willingness of patients and other reasons, protocol biopsy has not been widely applied in China. Currently, indicative biopsy is the main biopsy pattern. At present, the indications of puncture of indicative biopsy, the timing and necessity of puncture of protocol biopsy remain controversial. In this article, the classification of puncture biopsy after kidney transplantation and research progress on tissue biomarkers based on biopsy were reviewed, aiming to assist clinical diagnosis and targeted treatment of complications after kidney transplantation and provide reference for further improving the survival of renal allografts and recipients.

Effect of Dahuang Xiezhuo Prescription on Renal Tubular Function in Patients with IgA Nephropathy Complicated with Hyperuricemia / 中国实验方剂学杂志

ObjectiveTo observe the effect of Dahuang Xiezhuo prescription on the clinical symptoms， blood uric acid， and renal tubular function of patients with immunoglobulin A （IgA） nephropathy in stages 1-2 of chronic kidney disease （CKD） complicated with hyperuricemia （HUA）. MethodSixty patients with IgA nephropathy in stages 1-2 of CKD complicated with HUA of spleen and kidney deficiency and combined turbidity and blood stasis syndromes were randomly divided into an observation group and a control group， with 30 cases in each group. The patients in the control group received basic treatment， i.e.， losartan potassium tablets 50-100 mg/time， once per day， and sodium bicarbonate tablets 0.5 g/time， three times per day by oral administration， combined with low-salt， low-fat， and low-purine diet. The patients in the observation group received Dahuang Xiezhuo prescription on the basis of basic treatment， one dose per day， twice a day in the morning and evening with warm water. Both groups were treated for two months. The total scores of traditional Chinese medicine（TCM）syndrome， blood pressure， 24 h urinary protein （24 h UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr） ［glomerular filtration rate （eGFR） was calculated by CKD-epidemiology collaboration （CKD-EPI） formula］， serum uric acid （SUA）， and renal tubular function indexes ［urinary α1-microglobulin （α1-MG）， urinary β2-microglobulin （β2-MG）， urinary kidney injury molecule-1 （KIM-1）， and neutrophil gelatinase-associated lipocalin （NGAL）］ of the two groups before treatment and two months after treatment were recorded. The clinical efficacy of the two groups was evaluated two months after treatment. ResultAfter 2 months of treatment，the total effective rate in the observation group was 81.48%（22/27），higher than 50.00%（14/28） in the control group（χ2 =6.661，P<0.05）. The total scores of TCM syndrome， 24 h UTP， and SUA in the observation group and the observation group were lower than those before treatment （P<0.05）， and compared with the control group after treatment， the observation group decreased more significantly （P<0.05）. After treatment， the blood pressure in the observation group and the observation group was lower than that before treatment （P<0.05）， and there was no significant difference in blood pressure between the two groups after treatment. After treatment， the levels of urinary α1-MG， β2-MG， KIM-1， and NGAL in the two groups were lower than those before treatment （P<0.05）， and the observation group was lower than the control group after treatment （P<0.05）. There were no significant inter-group and intra-group differences in BUN， SCr， and eGFR levels before and after treatment. There were no obvious abnormalities in blood routine， liver function， and electrolytes before and after treatment in the two groups， and no adverse reactions such as allergies occurred. ConclusionDahuang Xiezhuo prescription can effectively improve the clinical symptoms of IgA nephropathy with HUA （CKD1-2） patients with spleen and kidney deficiency and combined turbidity and blood stasis syndromes， reduce blood uric acid level， alleviate renal tubular injury， and protect the kidney. The curative effect is better than that of basic treatment.

Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway / 中国中药杂志

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

The use of intraoperative mannitol during the laparoscopic nephrectomy in living kidney donor and the prevention of delayed graft function / Uso de manitol intraoperatorio durante la nefrectomía por laparoscopia en donante vivo de riñón y la prevención de función retardada del injerto

Background and objectives: The administration of mannitol during laparoscopic hand-assisted nephrectomy in the living donor has been controversial with various recommendations about it. This study aims to evaluate the effect of the intraoperative mannitol in the living kidney donor and the incidence of delayed graft function (DGF). Methods: This study was a retrospective observational study with living kidney transplant recipients and donors who underwent laparoscopic hand-assisted nephrectomy at Colombiana de Trasplantes from January 2015 to September 2019. We assessed the impact of mannitol administration in living donors on the main transplant outcomes such as DGF, urinary volume, acute rejection, and mortality at 3 months of follow-up. We performed a descriptive analysis of demographics and clinical variables in our cohort. Results: A total of 367 recipients were evaluated. The incidence of DGF was 5.9% without mannitol versus 6.2% with mannitol (p = 0.99). The acute rejection episodes (12.2% without mannitol versus 4.7% with mannitol) had a trend difference between the comparative groups, but it was still not significant in the bivariate analysis (p = 0.06). The mortality rate in the recipient was not significant (p = 0.69). The mean serum creatinine did not have significant differences at 1 and 3 months of follow-up comparing both groups. Conclusion: The use of mannitol in living donors does not have a significant impact on the incidence of DGF in kidney recipients. A trend of association between mannitol administration and reduced acute rejection episodes was observed, though it was not statistically significant.

Antecedentes y objetivo: La administración de manitol durante la nefrectomía laparoscópica en el donante vivo ha sido discutida con diversas recomendaciones. El objetivo es evaluar la administración de manitol intraoperatorio en el donante vivo de riñón y la incidencia de función retardada del injerto en el receptor. Métodos: Estudio observacional retrospectivo con receptores de riñón y donantes vivos que tuvieron nefrectomía laparoscópica en Colombiana de Trasplantes entre enero de 2015 a septiembre de 2019. Evaluamos el impacto de administrar manitol en los principales desenlaces del trasplante: función retardada del injerto, volumen urinario, rechazo agudo y mortalidad del receptor a los 3 meses post-trasplante. Se realizó un análisis descriptivo de las características demográficas y clínicas. Resultados: Se evaluaron 367 receptores con una incidencia de función retardada del injerto de 5.9% sin manitol versus 6.2% con manitol (p = 0,99), el rechazo agudo (12,2% sin manitol versus 4,7% con manitol) tuvo una tendencia de diferencia entre ambos grupos no significativa (p = 0,06) y la mortalidad del receptor tampoco mostró diferencias significativas (p = 0,69). La media de creatinina sérica al mes y 3 meses no tuvo diferencias significativas en los grupos. Conclusión: El uso de manitol en los donantes vivos de riñón no impactó significativamente la incidencia de función retardada del injerto en los receptores de trasplante. Se encontró una tendencia de asociación en la administración de manitol intraoperatorio y la reducción de los episodios de rechazo agudo al tercer mes post-trasplante en los receptores. No obstante, esta tendencia no tuvo la suficiente relevancia estadística.

Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway

BACKGROUND: Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1ß in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1ß and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. METHODS: Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1ß, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1ß and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. RESULTS: The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1ß in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1ß, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. CONCLUSIONS: Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

Hipomineralización Incisivo Molar en paciente pediátrico con acidosis tubular renal distal. Reporte de caso. Control y seguimiento por 14 años

Introducción: la hipomineralización incisivo molar es un defecto sistémico del desarrollo que afecta a uno o más primeros molares permanentes, se asocia con frecuencia a los incisivos permanentes, de etiología multifactorial y con diversas opciones de tratamiento. Objetivo: se presenta el caso de un paciente que presenta hipomineralización incisivo molar en sus primeros molares permanentes con antecedentes de haber padecido de acidosis tubular renal distal, dicha entidad puede ocasionar defectos en el esmalte. Reporte del caso: masculino de 7 años de edad diagnosticado con acidosis tubular distal a los 4 meses de edad, al momento de la consulta ya superado. En sus primeros molares permanentes se observan lesiones sugestivas de hipomineralización incisivo molar. Se evalúa clínica y radiográficamente. Se le realizan restauraciones con vidrio ionomérico revisadas en controles semestrales y a los 10 años se decide colocar resinas compuestas en los molares afectados. Se indican controles periódicos a los cuales asiste regularmente por 14 años. Conclusión: la identificación temprana de la Hipomineralización incisivo molar permitirá la aplicación de medidas preventivas para asegurar la permanencia de los dientes afectados en boca. Es Importante afianzar las prácticas higiénicas especialmente en las superficies afectadas, concomitantemente con la aplicación de materiales restauradores.

Introdução: a hipomineralização molar incisivo é um defeito sistémico do desenvolvimento que afeta um ou mais primeiros molares permanentes, está frequentemente associada a incisivos permanentes, de etiologia multifatorial e com várias opções de tratamento. Objetivo: é apresentado o caso de um paciente que apresenta hipomineralização molar incisivo em seus primeiros molares permanentes com histórico de ter sofrido acidose tubular renal distal, esta entidade pode causar defeitos de esmalte. Relato de caso: menino de 7 anos de idade diagnosticado com acidose tubular distal aos 4 meses de idade, à época da consulta já ultrapassado. Em seus primeiros molares permanentes, foram observadas lesões sugestivas de hipomineralização molar incisivo. É avaliado clínica e radiograficamente. Restaurações de ionômero de vidro foram realizadas, revisadas em controles semestrais, e aos 10 anos foi decidido colocar resinas compostas nos molares afetados. São indicados controles periódicos, que frequenta regularmente há 14 anos. Conclusão: a identificação precoce da hipomineralização molar incisivo permitirá a aplicação de medidas preventivas para garantir a permanência dos dentes acometidos na boca. É importante reforçar as práticas de higiene, principalmente nas superfícies afetadas, então com a aplicação de materiais restauradores.

Summary Introduction: molar incisor hypomineralization is a systemic developmental defect that affects one or more permanent first molars, is frequently associated with permanent incisors, of multifactorial etiology and with various treatment options. Objective: the case of a patient who presents molar incisor hypomineralization in his first permanent molars with a history of having suffered from distal renal tubular acidosis is presented, this entity can cause enamel defects Case report: 7-year-old male diagnosed with distal tubular acidosis at 4 months of age, at the time of the consultation he had already passed. In his first permanent molars, lesions suggestive of molar incisor hypomineralization were observed. It is evaluated clinically and radiographically. Glass ionomer restorations were performed, reviewed at six-monthly controls, and at 10 years it was decided to place composite resins on the affected molars. Periodic controls are indicated, which he regularly attends for 14 years. Conclusion: early identification of molar incisor hypomineralization will allow the application of preventive measures to ensure the permanence of affected teeth in the mouth. It is important to strengthen hygienic practices, especially on affected surfaces, concomitantly with the application of restorative materials.

Fanconi syndrome secondary to primary biliary cholangitis: a case report / 中华肾脏病杂志

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

Clinicopathological characteristics and prognosis analysis of mucinous tubular and spindle cell carcinoma of the kidney / 中华泌尿外科杂志

Objective:To explore the clinicopathological features and prognosis of renal mucinous tubular spindle cell carcinoma (MTSCC).Methods:The clinical data of 16 patients with MTSCC admitted to the First Affiliated Hospital of Zhengzhou University from July 2013 to July 2022 were retrospectively analyzed. There were six male cases and ten female cases. The mean age was (56.4±11.4) years old. Among them, 10 cases were asymptomatic, two complained of hematuria, three complained of lumbar pain, and one complained of lower limb pain. Twelve cases underwent preoperative enhanced CT examination, 6 cases of ultrasound examination, 3 cases of MRI examination, and 1 case of bone scan. Imaging manifestations showed that the masses were round or round-like with clear borders. Two cases combined with hemorrhage and three cases combined with calcification. Five cases showed exophytic growth, 10 cases partially exophytic, and 1 case completely endophytic. The maximum diameter of the tumor was (65.7±27.4) mm. The tumors were located in the left kidney in 11 cases and in the right kidney in 5 cases. The tumors were mildly delayed-enhancing under enhanced CT, long/short T1 signal mixed with long/short T2 signal under MRI, and diffusion-limited high signal under DWI. The tumors were hypoechoic masses without obvious blood flow signals under ultrasound. Twelve cases were diagnosed as renal occupying neoplasms, 2 cases were suggested as lack of blood supply renal tumor, and one was considered renal tumor rupture and bleeding. In one case, a bone scan suggested metastasis to the thoracic spine and pelvis. The metastatic renal tumor was diagnosed, and a renal puncture was performed to clarify the pathology. Eleven patients underwent laparoscopic radical nephrectomy, and 4 patients underwent partial nephrectomy. One case was metastasized without surgery and treated with apatinib mesylate and zoledronic acid.Results:The postoperative pathological specimens showed grayish, grayish-yellow, or grayish-red masses with a soft or medium texture. No perinephric, ureteral, or adrenal invasion was seen in all tumors. Microscopically, the tumor cells were round and ovoid. The tumor cells were arranged in tubular and striated shapes, and mucus pools were locally visible. No sarcomatous component was seen in all tumors. There were 9 patients with pT 1N 0M 0, 6 patients with pT 2N 0M 0, and 1 patient with pT 1N 0M 1. After operation, 2 patients with pT 2N 0M 0, who underwent laparoscopic radical nephrectomy were treated with pazopanib and sunitinib, respectively. All patients were followed up for a median of 50.7(25.8, 75.0)months, 15 patients were free of recurrent metastases, and 1 patient with pre-puncture metastasis died due to tumor progression of multiple pulmonary and bone metastases, with a survival of 16.9 months. Conclusions:Renal MTSCC is rare, mostly found on physical examination, with female patients predominantly, and imaging shows a lack of blood supply tumor. Surgery is the primary treatment method. Partial nephrectomy or radical nephrectomy could be chosen according to the tumor stage, kidney function, and patient's underlying condition, and patients have a good prognosis.

Effect of L-carnitine on ferroptosis in renal tubular epithelial cells induced by calcium oxalate / 中华泌尿外科杂志

Objective:To investigate the effect of L-carnitine on calcium oxalate-induced ferroptosis in renal tubular epithelial cells (HK-2).Methods:The effects of calcium oxalate(0, 2, 4 and 8 mmol/L) on the expression of ferroptosis-related protein long chain fatty acyl-CoA synthetase 4 (ACSL4), cystine/glutamate transporter(XCT) and glutathione peroxidase 4 (GPX4) in HK-2 cells were detected by Western blotting. The experiment was then divided into four groups: ①control group, cells were cultured in normal medium for 12 hours, then continued to use normal medium; ②L-carnitine group, cells were pretreated with medium containing 5mmol/L L-carnitine for 12 hours, then changed to medium containing 5mmol/L L-carnitine; ③calcium oxalate group, cells were cultured in normal medium for 12 hours, and then replaced with medium containing 4 mmol/L calcium oxalate; ④calcium oxalate+ L-carnitine group, the cells were pretreated with medium containing 5mmol/L L-carnitine for 12 h, and then replaced with 5mmol/L L-carnitine and 4mmol/L calcium oxalate medium. After changing the culture medium for 24 hours, the cells or supernatants were collected, and the expression levels of ferroptosis-related protein quinone oxidoreductase (NQO1), ACSL4, XCT and GPX4 were detected by Western blotting. The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde were detected by corresponding kit, and the level of reactive oxygen species in cells was detected by reactive oxygen species kit.Results:The results of Western blotting showed that the expression of ACSL4 protein in 0, 2, 4, 8 mmol/L calcium oxalate was 0.37±0.16, 0.68±0.16, 0.73±0.09, 0.89±0.03 respectively. The expression of XCT protein was 1.11±0.10, 0.91±0.14, 0.83±0.09, 0.80±0.07, respectively. The expression of GPX4 protein was 1.23±0.13, 0.99±0.17, 0.81±0.05, 0.72±0.06, respectively. Compared with 0mmol/L group, the expression of ACSL4 protein increased and the expression of XCT and GPX4 decreased in 2, 4 and 8 mmol/L groups, and the difference was more significant between 4 mmol/L group and 0 mmol/L group. So 4 mmol/L was taken as the optimal concentration for follow-up experiment. The levels of NQO1 in control group, L-carnitine group, calcium oxalate group and calcium oxalate+ L-carnitine group were (0.36±0.06, 0.54±0.05, 0.76±0.07, 0.90±0.03) respectively. There was significant difference between L-carnitine group and control group ( P<0.05). There was significant difference between calcium oxalate group and control group ( P<0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of ACSL4 in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (0.66±0.10, 0.58±0.08, 0.99±0.03, 0.77±0.09) respectively. There was no significant difference between L-carnitine group and control group(P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of XCT in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (0.93±0.08, 0.85±0.07, 0.76±0.06, 0.99±0.05). There was no significant difference between L-carnitine group and control group (P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of GPX4 in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (1.10±0.09, 1.09±0.09, 0.85±0.03, 0.99±0.02) respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of LDH in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine were (100.00±5.37)%, (99.50±6.38)%, (153.77±6.06)% and (132.50±5.58)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The SOD levels in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (100.00±5.79)%, (105.80±3.26)%, (44.74±7.60)% and (85.01±5.15)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The levels of GSH in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (100.00±4.73)%, (107.10±5.48)%, (53.49±3.98)% and (85.18±5.48)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.01). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.01). The levels of MDA in control group, L-carnitine group, calcium oxalate group and calcium oxalate + L-carnitine group were (100.00±2.36)%, (98.00±11.10)%, (129.11±2.59)% and (113.35±5.79)%, respectively. There was no significant difference between L-carnitine group and control group( P>0.05). There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.01). The fluorescence intensity of ferrous ion in control group, calcium oxalate group and calcium oxalate + L-carnitine group was (39.77±0.68) AU, (68.40±3.14) AU and (48.60±4.30) AU, respectively. There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.05). The fluorescence intensity of reactive oxygen species in control group, calcium oxalate group and calcium oxalate + L-carnitine group was (63.98±9.41) AU, (145.41±8.39) AU and (85.37±4.51) AU, respectively. There was significant difference between calcium oxalate group and control group ( P<0.01). There was significant difference between calcium oxalate + L-carnitine group and calcium oxalate group ( P<0.01). Transmission electron microscopy results showed that mitochondria were wrinkled, cristae were broken or disappeared in the calcium oxalate group compared to the control group, and a double-layer membrane structure was evident. DAPI staining showed that compared with the control group, some of the nuclei in the calcium oxalate group were significantly more damaged, while compared with the calcium oxalate group, the nuclei in the calcium oxalate + L-carnitine were significantly less damaged. The results of crystal adhesion test showed that compared with the control group, calcium oxalate crystals in the calcium oxalate group adhered to the cells in black-like particles and formed clusters. Compared with the calcium oxalate group, the calcium oxalate + L-carnitine showed less black particles adhering to the cells. Conclusions:L-carnitine may reduce the effects of oxidative stress and ferroptosis induced by calcium oxalate, thus reducing cell damage and crystal adhesion.

Large mucinous tubular and spindle cell carcinoma of left kidney: a case report / 中华泌尿外科杂志

In November 2019, we received and treated a patient with MTSCC of the left kidney. The tumor was located at the upper pole of the left kidney, with a size of 23.3 cm×18.0 cm×21.8 cm. She underwent transperitoneal radical nephrectomy. There was no local recurrence or distant metastasis during the follow-up of 3 years and 2 months. MTSCC of the kidney is a rare subtype of renal carcinoma, with slower disease progression, a clear and smooth rim, and fewer invasion or metastasis. Its final diagnosis should depend on pathology examination. Surgical treatment is the only effective intervention for this disease at present.

Assessment of Causality in Hospitalized Children With AminoglycosideRelated Nephrotoxicity

Objectives: To evaluate the incidence of aminoglycoside-related nephrotoxicity and ascertain drug causality and its risk factors. Methods: This prospective study was conducted from January, 2019 to January, 2021, and recruited 110 consecutively admitted children aged 1 month to 12 years, receiving aminoglycosides for ?4 days. Drug causality was assessed using Liverpool adverse drug reaction causality assessment tool. Results: 42 (38.2%) children developed acute kidney injury (AKI), with 71 (64.5%) having composite nephrotoxicity (AKI and/or tubular-dysfunction). Only 17 (15.5%) had AKI definitively attributable to aminoglycosides. Hypotension [OR 0.016 (95% CI 0.01-0.71), P=0.03], PRISM-III score 20-29% [OR 55.48 (95% CI 3.66-840.53), P=0.004] and post-surgery patients [OR 3.2 (95% CI 1.01-10.1), P=0.047] were independent predictors of AKI. Conclusions: Only a small proportion of children receiving aminoglycosides had AKI definitively attributable to the drug.

Hypokalemic paralysis due to distal renal tubular acidosistype 1 in patient of mucormycosison amphotericin B: a case report

A 42-year-old male patient who is a known case of DM and mucormycosison treatment presented with sudden onset difficulty in moving all 4 limbs followed by decreased depth of respiration for 4 hours. The patient was known case of DM for 10 years and was on OHA for the same, he had history of biopsy diagnosed rhino mucormycosis 4 months ago and was on treatment for the same. On initial examination the tone was hypotonic in all4 limbs along with power of 3+, respiration was shallow and patient was bedridden unable to stand on his own, he was ambulatory 6 days before presentingto hospital. Potassium-1.7 mEq/l, ABGA pH-7.18, HCO3-10 Meq/l, urine osmolality 220 mOsm/l, urine pH-7.0, potassium-to-creatinine rstio (K/Cr)-3.9 mEq/ml, urine K-22 mEq/ml. Distal RTA (dRTA) is the classical form of RTA, being the first described. DistalRTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalatedcellsof themedullary collecting ductof thedistalnephron.This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to apHof less than 5.3.This case study enumerates the potentially dangerous side effects of amphotericin B in patients which canprecipitate RTA type 1 leading to severe hypokalaemia and acidosis, thus all patients receiving amphotericin B should be cautiously warned regarding side effect of hypokalaemia and prophylactic potassium syrup supplementation may be given in predisposed patients.

Pathological findings in COVID-19: A conventional autopsy-based study from India

Background & objectives: Autopsy study has been considered the gold standard method for studying the effects of any disease on the body. Since COVID-19 is a novel disease, autopsy is crucial to understand its pathophysiology. This study was conducted to analyze the microscopic and macroscopic findings of various organs in COVID-19 and to associate those findings with clinical observations and laboratory findings. Methods: Conventional invasive autopsies were performed on 33 patients with COVID-19 from September 7, 2020 to December 23, 2020. All the organs were removed by routine dissection techniques and preserved in 10 per cent formalin. The tissues were processed and stained according to standard practices using haematoxylin-eosin (H & E) and periodic acid-schiff (PAS) stain. Results: The study included 28 males and 5 females with a median age of 61 yr (range 30-90 yr). Massive pulmonary oedema and thrombi in the lungs were the characteristic features macroscopically. On microscopic examination, diffuse alveolar damage in the exudative/proliferative phase was found in 29 (87.88%) cases. Among the other notable microscopic findings were bronchopneumonia and lung abscesses due to secondary bacterial infection (n=17, 51.52%), acute tubular injury (n=21, 63.64%) and thrombi in the lungs, heart, and kidneys. Interpretation & conclusions: COVID-19 primarily affected the respiratory and the renal systems in the vast majority of severely affected patients in our study. We also found signs of hypercoagulability, as evidenced by widespread thrombi in multiple organs, along with a raised d-dimer level and a hyperinflammatory state manifested by elevated inflammatory markers. Our autopsy findings and altered laboratory investigations support

Inhibition of ginsenoside Rb 1 on the epithelial-mesenchymal transition of renal tubular epithelial cells by regulating TGF-β1/Smad3 signaling pathway / 中国药房

OBJECTIVE To study the effects of ginsenoside Rb 1（G-Rb1）on epithelial-mesenchymal transition （EMT）of renal tubular epithelial cells and its potential mechanism. METHODS The growth factor β1（TGF-β1）10 ng/mL was used to induce EMT of human renal tubular epithelial cells HK- 2. The morphological changes of HK- 2 cells were observed after treated with 10， 20，30 μmol/L G-Rb1 for 48 h. The transcriptional activities of biovector SBE in human embryonic kidney cell HEK 293 were determined after 24 h treatment with 1.0，2.5，5.0，10，20，30 μmol/L G-Rb1. Effects of above concentration of G-Rb 1 on the viability of HK- 2 cells were determined after 24 h of treatment. mRNA expressions of α-smooth muscle actin （α-SMA），collagen Ⅰ （COL-Ⅰ）and fibronectin （FN）in HK- 2 cells were detected after treated with 10，20，30 μmol/L G-Rb1 for 24 h. The expressions of α-SMA，Smad3，p-Smad3，COL-Ⅰ，FN and E-cadherin were detected after treated with 10，20，30 μmol/L G-Rb1 for 24 h. RESULTS G-Rb1 of 10-30 μmol/L significantly inhibited TGF-β1-induced EMT in HK- 2 cells and the increase of transcriptional activities of biovector SBE induced by TGF-β1（P＜0.05），but had no effects on relative activities of HK- 2 cells（P＞0.05）. The protein and mRNA expressions of α-SMA，COL-Ⅰ and FN ， the protein expressions of Smad 3 and p-Smad 3 were significantly up-regulated induced by TGF-β1（P＜0.05），while the protein expression of E-cadherin was significantly down- regulated（P＜0.05）；G-Rb1 could effectively reverse aboveprotein or mRNA expressions. CONCLUSIONS G-Rb1 can protect renal tubular epithelial cells from EMT induced byxiezhishen TGF-β1 to a certain extent ，which may be related to inhibiting the activation of TGF-β1/Smad3 signaling pathway.

Predictive value of kidney injury markers for early DGF in kidney transplant recipients / 器官移植

Objective To evaluate the predictive values of serum neutrophil gelatinase-associated lipocalin (NGAL), urine NGAL, serum cystatin C (Cys-C) and serum creatinine (Scr) for early delayed graft function (DGF) in kidney transplant recipients. Methods Clinical data, blood and urine samples of 159 kidney transplant recipients were collected. All recipients were divided into the DGF group (n=42) and immediate graft function (IGF) group (n=117) according to the incidence of DGF. Clinical data of all recipients were analyzed. The changes of serum NGAL, urine NGAL, Cys-C and Scr levels were statistically compared between two groups. The predictive values of different markers for early DGF were assessed. Results Among 159 kidney transplant recipients, DGF occurred in 42 cases with an incidence rate of 26.4%. There were statistically significant differences in donor age, cold ischemia time of donor kidney and complement-dependent cytoxicity (CDC) between the two groups(all P < 0.05). Within postoperative 2 weeks, the serum NGAL levels in the DGF group were higher than those in the IGF group (all P < 0.05). The Cys-C, Scr and urine NGAL levels in the DGF group were higher compared with those in the IGF group within 3 weeks after kidney transplantation(all P < 0.001). Serum NGAL, urine NGAL, Cys-C and Scr levels had certain predictive values for early DGF in kidney transplant recipients. Cys-C yielded the highest predictive value with a cut-off value of 4.73 mg/L, sensitivity of 0.833, specificity of 0.812 and area under the curve (AUC) of 0.895. Conclusions Cys-C has higher predictive value for early DGF in kidney transplant recipients compared with serum NGAL, urine NGAL and Scr.

The role of the fat mass and obesity-associated protein in ischemia-reperfusion injury of human renal tubular epithelial cells / 中华实用儿科临床杂志

Objective:To explore the role of the fat mass and obesity-associated protein (FTO) in human renal tubular epithelial cells (HK-2) suffering ischemia-reperfusion injury (IRI).Methods:The in vitro IRI mo-del was established in HK-2 cells by induction with antimycin A, A23187 and 2-deoxy-D-glucose.The cells were divided into control group and ischemia-reperfusion group (I/R group). The mRNA and protein expressions of FTO, B-cell lymphoma / leukemia 2(Bcl-2)-associated X(Bax), Bcl-2 and cleaved cysteinyl aspartate specific proteinase(cleaved Caspase-3) in HK-2 cells before and after IRI were detected by real-time fluorescent quantitative PCR(qPCR) and Western blot, respectively.Cell apoptosis was measured using flow cytometry.The level ofe N 6-methy-ladenosine (m 6A) RNA was detected by colorimetry. Results:(1) The mRNA expressions of FTO (0.15±0.05 vs.1.00±0.23) and Bcl-2 (0.14±0.07 vs.1.02±0.25) in I/R group were significantly lower than those in control group; While those of Bax (3.10±0.35 vs.1.00±0.13) and cleaved Caspase-3 (4.21±0.56 vs.1.00±0.09) were significantly higher ( t=6.28, 5.84, -9.83, and -9.84, respectively, all P<0.01). (2) The protein expressions of FTO (0.69±0.14 vs.1.37±0.02) and Bcl-2 (0.50±0.12 vs.1.25±0.21) were significantly lower in I/R group than those of control group; While those of Bax (1.04±0.08 vs.0.57±0.06) and cleaved Caspase-3 (0.99±0.05 vs.0.36±0.07) were significantly higher ( t=8.10, 5.49, -8.22, and -12.09, respectively, all P<0.05). (3) Compared with the control group, the apoptosis rate of HK-2 cells in I/R group was significantly higher [(61.70±1.01)% vs.(0.16±0.10)%, t=63.80, P<0.01]. (4) Compared with the control group, the percentage of m 6A modification level in total RNA in I/R group was significantly higher [(3.13±0.21)% vs.(1.10±0.26)%, t=-10.61, P<0.01]. Conclusions:FTO-mediated RNA m 6A modification may affect renal IRI by regulating the apoptosis of HK-2 cells.