Thyroid function and polycystic ovary syndrome: a Mendelian randomization study.

Background: Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. Methods: Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses. Results: The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS. Conclusions: Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.

Preparation and evaluation of the immune efficacy of an inactivated fowl adenovirus 8a serotype oil emulsion vaccine.

In recent years, fowl adenovirus (FAdV) transmission has significantly increased worldwide, leading to substantial economic losses in the poultry industry. The virus causes hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH). The prevalent FAdV strains in China are FAdV-4, FAdV-8a, FAdV-8b, and FAdV-11. Vaccines for FAdV-4 and FAdV-8b, which prevent HHS and IBH, are available commercially, but no vaccine exists for FAdV-8a. To address this issue, we developed a vaccine using an oil emulsion to inactivate the FAdV-8a serotype. Additionally, we built a fluorescence quantitative PCR for the detection of the virus. The lowest concentration detected was 4.11 × 101 copies/µL. The study's results illustrated that the FAdV-8a oil emulsion vaccine effectively produced significant antibodies and offered ample protection for poultry. This vaccine can potentially limit the transmission of IBH resulting from FAdV-8a in China.

Prenatal Ultrasound Diagnosis and Clinical Analysis of Fetal Small Bowel Obstruction.

BACKGROUND: Fetal small bowel obstruction (SBO) is a serious condition with high morbidity and mortality rates. Prenatal ultrasound is an important tool for detecting SBO, but the optimal cutoff value for intestinal diameter remains undefined. OBJECTIVE: This study aimed to investigate the ultrasonic characteristics of fetal SBO and determine the optimal cutoff value for intestinal diameter to enhance prenatal ultrasound diagnosis. METHODS: We retrospectively analyzed the ultrasonic characteristics and postpartum data of 76 cases diagnosed with SBO. Receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff value for dilated intestinal diameter. RESULTS: Among the 76 cases, 31 displayed the "double bubble sign" on ultrasound, with 20 cases identified as annular pancreas, 6 as duodenal atresia, and 5 as duodenal membranous stenosis. In 45 cases, the lesions were located in the jejunal or ileal segment and exhibited intestinal dilatation above the lesion site, including 27 cases of small bowel atresia, 7 cases of membranous jejunal stenosis, and 11 cases of small bowel volvulus. Out of the 76 cases, 9 showed no abnormalities after birth. ROC curve analysis determined optimal cutoff values of 17.5mm and 10.5mm for predicting "double bubble sign" lesions in the gastric and duodenal widths. For predicting small intestinal dilatation, the optimal cutoff values for dilated width and length of the intestinal tube were 11.5mm and 21.5mm, respectively, with high sensitivity and specificity. CONCLUSION: Ultrasonic imaging and changes in intestinal diameter provide valuable information for prenatal diagnosis and management of SBO. Establishing these cutoff values can improve the accuracy of prenatal ultrasound diagnosis for SBO.

Accuracy of lung and diaphragm ultrasound in predicting infant weaning outcomes: a systematic review and meta-analysis.

Background: Although lung and diaphragm ultrasound are valuable tools for predicting weaning results in adults with MV, their relevance in children is debatable. The goal of this meta-analysis was to determine the predictive value of lung and diaphragm ultrasound in newborn weaning outcomes. Methods: For eligible studies, the databases MEDLINE, Web of Science, Cochrane Library, PubMed, and Embase were thoroughly searched. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) method was used to evaluate the study's quality. Results were gathered for sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the curve of summary receiver operating characteristic curves (AUSROC). To investigate the causes of heterogeneity, subgroup analyses and meta-regression were conducted. Results: A total of 11 studies were suitable for inclusion in the meta-analysis, which included 828 patients. The pooled sensitivity and specificity of lung ultrasound (LUS) were 0.88 (95%CI, 0.85-0.90) and 0.81 (95%CI, 0.75-0.87), respectively. The DOR for diaphragmatic excursion (DE) is 13.17 (95%CI, 5.65-30.71). The AUSROC for diaphragm thickening fraction (DTF) is 0.86 (95%CI, 0.82-0.89). The most sensitive and specific method is LUS. The DE and DTF were the key areas where study heterogeneity was evident. Conclusions: Lung ultrasonography is an extremely accurate method for predicting weaning results in MV infants. DTF outperforms DE in terms of diaphragm ultrasound predictive power.

EditorialAssignment.

INTRODUCTION: Primary membranous nephropathy (PMN) is a major cause of nephrotic syndrome in adults. Rituximab has been recommended in the treatment of PMN by the updated Kidney Disease Improved Outcome guideline. However, the optimal dosing regimen of rituximab for the initial treatment of patients with PMN is unclear. METHODS AND ANALYSIS: A comprehensive screening will be performed by searching PubMed, Embase and the CENTRAL (Cochrane Central Register of Controlled Trials) without language restriction. Studies evaluating the efficacy of rituximab monotherapy using the following types of dosing regimens will be included: high-dose regimen; standard regimen and low-dose regimen. Studies with less than 10 participants will be excluded. The primary outcome is the remission rate at 12 months. The secondary outcomes are remission rate at 6 and 24 months, complete remission rate at 6, 12 and 24 months, relapse at 6, 12 and 24 months, and side effects. Risk of Bias In Non-randomised Studies of Interventions tool will be used to assess the risk of bias for non-randomised studies and the Cochrane risk of bias assessment tool will be used for randomised controlled trials. The pooled remission rate, complete remission rate, relapse rate and side effects will be estimated using the metaprop command. All analyses will be calculated using Stata software (V.15.0; StataCorp). ETHICS AND DISSEMINATION: Ethics approval is not required. The results of our study will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42022319401.

Association of serum 25-hydroxy vitamin D with gait speed and handgrip strength in patients on hemodialysis.

BACKGROUND: Muscle dysfunction is prevalent in dialysis patients. Gait speed and handgrip strength are simple and reliable methods of assessing muscle function. Numerous observational studies have linked 25-hydroxy vitamin D[25(OH)D] status with gait speed and handgrip strength in populations without kidney diseases. This study aimed to evaluate the potential associations of 25(OH)D status with gait speed and handgrip strength in patients on hemodialysis. METHODS: In this observational cross-sectional study, demographic data, biological data, and dialysis parameters were collected. Gait speed and handgrip strength were measured. Multiple linear regression and logistic regression analysis were used to investigate the relationship of 25(OH)D status with gait speed and handgrip strength after adjusting for potential confounders. RESULTS: Overall, a total of 118 participants undergoing hemodialysis were included. Seventy-one (60.2%) participants were male. The median 25(OH)D status in participants was 11.58 (interquartile range: 8.51 to 15.41) ng/ml. When controlling for age, gender, dialysis vintage, and other confounders with a p-value < 0.15 in univariate analyses, 25(OH)D was significantly positively associated with gait speed (ß = 0.16, 95% CI 0.05 to 0.28, p = 0.006) and handgrip strength (ß = 3.83, 95% CI 1.09 to 6.56, p = 0.007). CONCLUSION: Our study showed that 25(OH)D status seemed to be associated with gait speed and handgrip strength in patients on hemodialysis. However, these results were not robust. The relationships between 25(OH)D status and gait speed and handgrip should be further explored.

Porcine Epidemic Diarrhea Virus Infection Subverts Arsenite-Induced Stress Granules Formation.

Stress granules (SGs) are dynamic cytoplasmic protein-RNA structures that form in response to various stress conditions, including viral infection. Porcine epidemic diarrhea virus (PEDV) variant-related diarrhea has caused devastating economic losses to the swine industry worldwide. In this study, we found that the percentage of PEDV-infected cells containing SGs is nearly 20%; meanwhile, PEDV-infected cells were resistant to sodium arsenite (SA)-induced SGs formation, as demonstrated by the recruitment of SGs marker proteins, including G3BP1 and TIA1. Moreover, the formation of SGs induced by SA treatment was suppressed by PEDV papain-like protease confirmed by confocal microscopy. Further study showed that PEDV infection disrupted SGs formation by downregulating G3BP1 expression. Additionally, PEDV replication was significantly enhanced when SGs' assembly was impaired by silencing G3BP1. Taken together, our findings attempt to illuminate the specific interaction mechanism between SGs and PEDV, which will help us to elucidate the pathogenesis of PEDV infection in the near future.

Diagnostic Ideas and Management Strategies for Thrombocytopenia of Unknown Causes in Pregnancy.

Objective: To summarize the clinical characteristics and treatment options together with the maternal and neonatal prognoses in women with different degrees of thrombocytopenia of unknown causes during pregnancy. Materials and Methods: One hundred twenty-nine cases meeting the inclusion and exclusion criteria were retrospectively analyzed. Patients were divided into group A (50*109/L) and group B (50*109/L to 100*109/L) according to the lowest level of platelet count during pregnancy. Patients were divided into those found to have thrombocytopenia in the relatively early, middle, and late stages according to the detection period of maternal thrombocytopenia during pregnancy. Results: There were 72 cases in group A, and 57 cases in group B. There existed statistically significant differences in terms of the proportion of primipara, the proportion with a history of thrombocytopenia, and the median length of pregnancy between the two groups (p < 0.05). The proportion of patients with severe thrombocytopenia as an indication for cesarean delivery was higher in group A than in group B (p < 0.05). More cases were detected at the relatively early stages of pregnancy in group A than in group B (p < 0.05). There was no difference in neonatal hemorrhage and events of thrombocytopenia between the two groups. Conclusion: Patients with platelet counts below 50*109/L were mostly primipara with a history of thrombocytopenia, most often detected at a relatively early stage of pregnancy, and continued pregnancy might lead to aggravation of the disease. Combination therapy was required for patients with platelet counts below 30*109/L to maintain the platelet counts within a safe range. Cesarean delivery was selected to terminate the pregnancies, and platelet counts should be raised above 50*109/L before surgery. Close monitoring was required for those with platelet counts above 30*109/L. There was no direct correlation between the maternal and neonatal platelet counts.

Reproduction and pathogenesis of short beak and dwarfish syndrome in Cherry Valley Pekin ducks infected with the rescued novel goose parvovirus.

Since the outbreak of short beak and dwarfish syndrome (SBDS) in Cherry Valley Pekin ducks in China, novel goose parvovirus (NGPV) has been isolated. Till now, little is known about the NGPV pathogenesis toward Cherry Valley Pekin ducks. Besides, due to detection of duck circovirus co-infection in SBDS clinical cases, whether sole NGPV infection can reproduce all the typical symptoms of SBDS remains unclear. In this study, based on the NGPV isolate SDJN19, an infectious plasmid clone pJNm containing the entire SDJN19 genome was constructed. Transfection of pJNm in embryonated duck eggs resulted in generation of the infectious virus carrying the genetic marker, named rJNm. rJNm infection of 2-day-old Cherry Valley Pekin ducks reproduced all the typical signs of SBDS, including beak atrophy, tongue protrusion, and growth retardation. rJNm can infect Cherry Valley Pekin ducks through the horizontal transmission route, and the infected ducks exhibited the characteristic SBDS symptoms. A high level of serum precipitation antibodies (above 5log2) were induced in the surviving ducks, however, high viral loads were still detected in the duck organs, suggesting persistent NGPV infection in ducks. By incorporating the homologous Rep1 and VP1 gene from classical GPV, two chimeric viruses rJN-cVP1 and rJN-cRep1 were generated. Duck infection tests revealed that the non-structural protein Rep1 played a crucial role in the NGPV pathogenicity. The present result lays a solid foundation for further exploring how the Rep protein contributes to the NGPV pathogenesis.

Generation of duck Tembusu virus using a simple reverse genetic system in duck embryo fibroblast cells.

Outbreaks of duck Tembusu virus (DTMUV) have caused serious economic losses in China since 2010. In this study, an infectious clone of the DTMUV BZ-2010strain, isolated from layer cherry duck in China, was constructed using the bacterium-free infectious subgenomic-amplicons method. The subgenomic-amplicons of the human cytomegalovirus promoter (pCMV) at the 5' terminus of the first DNA fragment, the entire genome of DTMUV, and the hepatitis delta ribozyme followed by the simian virus 40 polyadenylation signal (HDR/SV40pA) at the 3' terminus of the last DNA fragment were synthesized and amplified by PCR in three DNA fragments. The pCMV and HDR/SV40pA were used to drive the viral RNA transcription and generate a full-length RNA transcript of the virus, and were found to be effective in reassembling DTMUV in duck embryo fibroblast cells. The RNA transcripts from the infection clone were infectious in duck embryo fibroblast cells, generating the reconstituted DTMUV. This study provided a valuable reverse genetic tool for the further study DTMUV pathogenesis.

Molecular characteristics and phylogenetic analysis of novel goose parvovirus strains associated with short beak and dwarfism syndrome.

Short beak and dwarfism syndrome (SBDS) emerged in Cherry Valley duck flocks in China in 2015, and novel goose parvovirus (NGPV) was shown to be the etiological agent of SBDS. To date, it is not known whether SBDS-related NGPV isolates possess common molecular characteristics. In this study, three new NGPV strains (namely, SDHT16, SDJN19, and SDLC19) were isolated from diseased ducks showing typical signs of SBDS and successfully passaged in embryonated goose or Cherry Valley duck eggs. The complete genome sequences of these NGPV strains were 98.9%-99.7% identical to each other but showed slightly less similarity (95.2%-96.1% identity) to classical GPV strains. A total of 16 common amino acid substitutions were present in the VP1 proteins of six NGPV strains (SDHT16, SDJN19, SDLC19, QH, JS1, and SDLC01) compared with the classical Chinese GPV strains, nine of which were identical to those found in European GPV strain B. The non-structural protein Rep1 of the six NGPV strains had 12 common amino acid substitutions compared with the classical GPV strains. Phylogenetic analysis indicated that the Chinese NGPV strains clustered with the European SBDS-related NGPV strains, forming a separate branch that was distinct from the group formed by the classical GPV strains. The present study shows the common molecular characteristics of NGPV isolates and suggests that the Chinese NGPV isolates probably share a common ancestor with European SBDS-related NGPV strains.

Novel duck reovirus exhibits pathogenicity to specific pathogen-free chickens by the subcutaneous route.

To study the pathogenicity of new duck reovirus (NDRV) to chickens, eighty 3-day-old SPF chickens were equally divided into two groups. The experimental group was inoculated with a NDRV challenge strain of 100 µL (10-5.00 ELD50/0.1 mL) by the subcutaneous (s.c.) route, and the control group was inoculated with 100 µL of sterile phosphate-buffered saline (PBS) by the same route. In the experimental group, chickens exhibited introflexion of claws, performing of splits, stunting syndrome, weight loss and death. Gross lesions such as enlargement and yellowish-white focal necroses were observed in the liver and spleen. Microscopic changes were typical including varying degrees of hepatocyte steatosis and necrosis, splenic lymphocyte necrosis, interstitial pneumonia. Viral loads were detected in lung, liver, heart, spleen, duodenum, burse and kidney. The liver and spleen viral loads remained a much higher level and maintained for a longer time, suggesting that these tissues might be the target organs. In summary, NDRV can cause systemic infections and death in chickens, which indicated that chickens may be infected by NDRV in poultry production.

New insights into enhanced anaerobic degradation of coal gasification wastewater (CGW) with the assistance of magnetite nanoparticles.

Magnetite nanoparticles (Fe3O4 NPs) was firstly used to enhance pollutants removal during coal gasification wastewater (CGW) treatment in anaerobic digestion (AD) system. Bench-scale results revealed that 200 mg/L and 20-40 nm of Fe3O4 NPs addition resulted in a maximum removal capacity of total phenol (TPh) at a temperature of 36 °C and hydraulic retention time (HRT) of 36 h. Meanwhile, Fe3O4 NPs addition reduced the oxidation reduction potential (ORP) values and biological toxicity, and enhanced the stability of AD system. Pilot-scale results showed that the TPh and chemical oxygen demand (COD) removal efficiency (53% and 49%) were obtained with the optimal dosage of Fe3O4 NPs. Moreover, electron nanowires may be established with Fe3O4 NPs assisted to perform direct interspecies electron transfer (DIET) among Geobacter, Pseudomonas and Methanosaeta species, and finally enhanced the pollutants removal efficiency.

Meta-analysis of heparin combined with aspirin versus aspirin alone for unexplained recurrent spontaneous abortion.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) frustrates women of childbearing age profoundly, and effective therapies are particularly important. OBJECTIVE: To compare the efficacy of heparin combined with aspirin and aspirin alone for URSA. SEARCH STRATEGY: Electronic databases (PubMed, Medline, Web of Science, Clinical key and Cochrane Library) were searched for relevant studies from database inception to August 2019. SELECTION CRITERIA: Studies of women of childbearing age with at least two consecutive abortions were included. DATA COLLECTION AND ANALYSIS: Relevant items were extracted, tabulated, and subjected to STATA for data analysis. Study women were divided into group A (taking heparin plus aspirin) and group B (taking aspirin alone). The primary outcome was the rate of live birth. MAIN RESULTS: Women from eight randomized controlled trials were included: 493 in group A and 501 in group B. The number of live births was significantly higher in group A (P=0.003). The result remained the same in subgroup analysis by presence of antiphospholipid antibodies. Among women who had a live birth, gestational age at delivery tended to be older in group B (P=0.054). No differences in birthweight or intrauterine growth restriction were observed. Adverse effects were sporadically reported. CONCLUSION: Among women with URSA, heparin combined with aspirin increased the live birth rate as compared with aspirin alone. There was a beneficial tendency of taking aspirin-only to prolong gestation week.

Surgical Decompression versus Conservative Treatment in Patients with Malignant Infarction of the Middle Cerebral Artery: Direct Comparison of Death-Related Complications.

BACKGROUND: Surgical decompression and conservative treatment are routinely used in the treatment of patients with malignant infarction of the middle cerebral artery (MIMCA). However, efficacy and safety are controversial. The purpose of this study is to systematically compare the clinical outcomes between surgical decompression and conservative treatment in patients with MIMCA. METHODS: This study retrieved available academic randomized controlled trials (RCTs) comparing the clinical outcomes between surgical decompression and conservative treatment in patients with MIMCA from the databases of ScienceDirect, Cochrane Library, Embase, and PubMed. The references of previous reviews and related clinical studies were manually checked to retrieve potential literature that was not involved in our electronic search results. RESULTS: A total of 7 RCTs were included in the study. The overall number of participants in the surgical decompression group was 165, whereas it was 173 in the conservative treatment group. The results revealed that the surgical decompression group was related to a lower incidence of 1-year death (odds ratio [OR], 0.192; 95% confidence interval [CI], 0.119-0.309; P < 0.001), 1-year death in patients >60 years of age (OR, 0.202; 95% CI, 0.097-0.421; P < 0.001), 1-year death in patients <60 years of age (OR, 0.145; 95% CI, 0.069-0.301; P < 0.001), 1-year death in patients treated within 48 hours of stroke onset (OR, 0.159; 95% CI, 0.090-0.282; P < 0.001), and modified Rankin Scale (mRS) score ≤3 (OR, 2.082; 95% CI, 1.185-3.658; P < 0.001). CONCLUSIONS: Based on current evidence for patients with MIMCA, decompressive surgery not only is a life-saving therapy but also reduces the incidence of mortality without increasing the risk of severe disability.

Loss of transforming growth factor-ß1 in epithelium cells affects enamel formation in mice.

OBJECTIVES: In order to understand the specific in vivo function of transforming growth factor-beta1 (TGF-ß1), we successfully established aTGF-ß1 deficient mouse model using a conditional knockout method. In the present study, we aimed to further understand the potential role of TGF-ß1 in enamel formation. DESIGN: Transgenic mice withoutTGF-ß1 in epithelial cells were generated. Scanning electron microscopy and micro-computed tomography analysis were used to detect the dental appearance, enamel microstructure and tooth density. Histological analysis was used to examine the residual organic matrix of enamel. Quantitative real-time polymerase chain reaction was used to analyze the expressions of enamel matrix proteins at the mRNA level. RESULTS: The enamel of mandibular molars and incisors inTGF-ß1 conditional knockout mice displayed severe attrition and lower density compared with the wild-type littermates. A slender microstructure of enamel rod was observed, and enamel matrix proteins were retained in the enamel space at the maturation stage in conditional knockout mice. Moreover, the expressions of enamel matrix protein-encoding genes, such as amelogenin (Amelx), ameloblastin (Ambn), Enamelin (Enam) and matrix metalloproteinase-20 (Mmp-20), were increased in enamel organs of conditional knockout mice. On the other hand, the expressions of Amelotin (Amtn), kallikrein-related peptidase-4 (Klk4), C4orf26 and WD repeat-containing protein 72 (Wdr72) were dramatically decreased at the transition and maturation stages. CONCLUSIONS: TGF-ß1 played an important role in enamel mineralization through decreasing synthesis ofAmelx, Ambn and Enam and increasing synthesis of Klk4, Amtn, Corf26 and Wdr72.

Nonrigid Registration of Prostate Diffusion-Weighted MRI.

Motion and deformation are common in prostate diffusion-weighted magnetic resonance imaging (DWI) during acquisition. These misalignments lead to errors in estimating an apparent diffusion coefficient (ADC) map fitted with DWI. To address this problem, we propose an image registration algorithm to align the prostate DWI and improve ADC map. First, we apply affine transformation to DWI to correct intraslice motions. Then, nonrigid registration based on free-form deformation (FFD) is used to compensate for intraimage deformations. To evaluate the influence of the proposed algorithm on ADC values, we perform statistical experiments in three schemes: no processing of the DWI, with the affine transform approach, and with FFD. The experimental results show that our proposed algorithm can correct the misalignment of prostate DWI and decrease the artifacts of ROI in the ADC maps. These ADC maps thus obtain sharper contours of lesions, which are helpful for improving the diagnosis and clinical staging of prostate cancer.

Knockdown of SKA1 gene inhibits cell proliferation and metastasis in human adenoid cystic carcinoma.

The spindle and kinetochore-associated complex subunit 1(SKA1) is a newly discovered gene, which has been associated with mitosis and tumorigenesis. However, its role insalivary adenoid cystic carcinoma (SACC) is still unknown, and the invasive and metastatic mechanism in SACC is still unclear. To explore the molecular mechanism of SKA1 in the process of malignant proliferation and metastasis in adenoid cystic cancer (ACC) cells, we employed lentivirus-mediated short hairpin RNA to knockdown SKA1 in SACC-83 cells. The results demonstrated that the lentivirus-mediated shRNA-targeting SKA1 lead to a significant down-regulation of SKA1 expression. Knockdown of SKA1 inhibited cell proliferation, cell invasion, migration and the cell cycle arrest. Furthermore, knockdown of SKA1 reduced the Ndc80, CDK4, Cyclin D1, Cyclin E1, Cyclin B1 and matrix metalloproteinase-9 (MMP-9) protein expression, but increased the p27 protein expression. These findings indicated that SKA1 might be a promising target for cancer gene therapy in human ACC.

L-Carnitine Ameliorates the Decrease of Aquaporin 2 Levels in Rats with Cisplatin-Induced Kidney Injury.

BACKGROUND: It has been found that L-carnitine ameliorated cisplatin-induced acute kidney injury (AKI) in rats. However, the detailed role of L-carnitine in improving the renal urinary concentration function in cisplatin-induced AKI is not fully understood. METHODS: In this study, 30 Sprague-Dawley rats were divided randomly into 5 groups: control, cisplatin (CIS), L-carnitine (CAR), L-carnitine plus cisplatin (CAR + CIS), and cisplatin plus L-carnitine (CIS + CAR) groups. Cisplatin (7 mg/kg) and L-carnitine (300 mg/kg) were injected intraperitoneally. Urine (24 h) and blood samples were collected to analyze renal urinary concentrating function. Immunoblotting, confocal laser microscopy, and enzyme-linked immunosorbent assays were used to assess the level and localization of the water channel aquaporin (AQP) 2, and levels of stimulatory G protein α subunit (GSα protein), arginine vasopressin (AVP) receptor 2, adenylyl cyclase and serum AVP. RESULTS: Renal urinary concentrating function was improved by L-carnitine in rats with cisplatin-induced AKI. AQP2 expression, which decreased after cisplatin treatment, was improved by L-carnitine in different regions of the kidney. Moreover, our data indicated that L-carnitine could increase AQP2 accumulation at the apical plasma membranes of the renal-collecting ducts. Finally, intervention with L-carnitine effectively improved the expression of AQP2 upstream signaling proteins, such as GSα protein, adenylyl cyclase, and serum AVP levels in rats with cisplatin-induced AKI. CONCLUSION: L-carnitine resolves the cisplatin-induced urinary concentration defect, which may occur by increasing AVP/cyclic adenosine monophosphate/AQP2 levels, indicating the potential use of L-carnitine to ameliorate the renal urinary concentration effect in cancer patients treated with cisplatin.

Uremia and thrombotic microangiopathy: conditions that may havethe same manifestation.

In this article, we present the case of a man with uremia. Laboratory testing revealed thrombocytopenia, erythrocyte fragmentation, elevated lactate dehydrogenase, and malignant hypertension, manifestations that are similar to thrombotic microangiopathy (TMA). Thromboasthenia, manifested as a decrease in the platelet aggregation rate, was also noted. Regular hemodialysis (3 times per week) improved the patient's thrombocytopenia and thromboasthenia. This case supports the conclusion that uremic toxin, which can be removed by hemodialysis, inhibits the quantity and quality of platelets. We believe that the platelet aggregation rate can be a useful tool in distinguishing uremia from TMA.