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The aim of this study is to clarify the association between lymphovascular invasion (LVI) and/or perineural invasion (PNI) and the clinical characteristics and prognostic importance of rectal cancer, to provide a basis for early adjuvant treatment of rectal cancer. We retrospectively analyzed patients diagnosed with rectal cancer. This study involved rectal cancer tissue samples were obtained by surgical methods. Data on histological form, tumor classification, tumor size, gross growth pattern, blood and lymphatic vessel invasion, and PNI of the slice by HE staining were obtained from pathological examination. Immunohistochemical analysis of tissue samples was performed to determine p53 and EGFR expressions. There were 330 rectal cancer patients included in the study. LVI and/or PNI can be used as a high-risk factor for the prognosis of rectal cancer, predict prognostic survival, and guide adjuvant therapy. The detection rates of LVI and PNI were 32.1% and 16.1%. Differentiation grade, Union for International Cancer Control staging, tumor-lymph node-metastasis staging are significantly related to LVI or PNI. Multivariate logistic regression analysis shows that poor differentiation and N ≥ 1 can be used as independent risk factors and predictive factors for LVI. At the same time, poor differentiation and T 3 is an independent risk factor for PNI. Only poor differentiation is the risk factor for poor prognosis in Cox risk regression analysis. In addition, the simultaneous occurrence of LVI and PNI is an independent prognostic factor.

Background Both Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants. Methods Using high‐throughput DNA sequencing and Sanger sequencing, we detected variants in a female with clinically suspected PS. A minigene splicing assay was performed to assess the effect of LAMB2 intron 20 c.2885‐9C>A on RNA splicing. We also performed the immunohistochemical analysis of laminin beta‐2 in kidney tissues. Results Two novel LAMB2 heteroallelic variants were found: a paternally inherited variant c.2885‐9C>A in intron 20 and a maternally inherited variant c. 3658C>T (p. (Gln1220Ter)). In vitro minigene assay showed that the variant c.2885‐9C>A caused erroneous integration of a 7 bp sequence into intron 20. Immunohistochemical analysis revealed the absence of glomerular expression of laminin beta‐2, the protein encoded by LAMB2. Conclusion We demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2., We demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2.

Renal hypodysplasia and cystic kidney diseases, the common non-glomerular causes of pediatric chronic kidney disease (CKD), are usually diagnosed by their clinical and imaging characteristics. The high degree of phenotypic heterogeneity, in both conditions, makes the correct final diagnosis dependent on genetic testing. It is not clear, however, whether the frequencies of damaged alleles vary among different ethnicities in children with non-glomerular CKD, and this will influence the strategy used for genetic testing. In this study, 69 unrelated children (40 boys, 29 girls) of predominantly Han Chinese ethnicity with stage 2–5 non-glomerular CKD caused by suspected renal hypodysplasia or cystic kidney diseases were enrolled and assessed by molecular analysis using proband-only targeted exome sequencing and array-comparative genomic hybridization. Targeted exome sequencing discovered genetic etiologies in 33 patients (47.8%) covering 10 distinct genetic disorders. The clinical diagnoses in 13/48 patients (27.1%) with suspected renal hypodysplasia were confirmed, and two patients were reclassified carrying mutations in nephronophthisis (NPHP) genes. The clinical diagnoses in 16/20 patients (80%) with suspected cystic kidney diseases were confirmed, and one patient was reclassified as carrying a deletion in the hepatocyte nuclear factor-1-beta gene (HNF1B). The diagnosis of one patient with unknown non-glomerular disease was elucidated. No copy number variations were identified in the 20 patients with negative targeted exome sequencing results. NPHP genes were the most common disease-causing genes in the patients with disease onsets above 6 years of age (14/45, 31.1%). The children with stage 2 and 3 CKD at onset were found to carry causative mutations in paired box gene 2 (PAX2) and HNF1B gene (11/24, 45.8%), whereas those with stage 4 and 5 CKD mostly carried causative mutations in NPHP genes (19/45, 42.2%). The causative genes were not suspected by the kidney imaging patterns at disease onset. Thus, our data show that in Chinese children with non-glomerular renal dysfunction caused by renal hypodysplasia and cystic kidney diseases, the common causative genes vary with age and CKD stage at disease onset. These findings have the potential to improve management and genetic counseling of these diseases in clinical practice.

The study aims to reveal the clinical significance of perineural invasion (PNI) for gastric cancer prognosis and determine the risk factors of PNI in gastric cancer. This study retrospectively analyzed 350 patients who were diagnosed with GC and underwent curative surgical resection. Variables used to analyze survival included gender, age, degree of differentiation, T classification, lymph node metastasis, lymphovascular invasion, nerve invasion, mucinous adenocarcinoma component, and signet ring cell carcinoma component. The tumors of all patients were surgically resected. All resected specimens were stained with hematoxylin-eosin and immunohistochemical. The data for the patient's lymphovascular invasion and PNI came from the collected pathological reports. The results of the survival analysis showed that T staging (P.001), lymph node metastasis (P.001), lymphovascular invasion (P = .013), PNI (P = .001), and signet ring cell carcinoma components (P = .046) affect the survival time and have a statistically significant difference. Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .014). T staging (P = .006) and lymph node metastasis (P = .013) were independent prognostic parameters too. Using the Spearman correlation analysis, the following clinicopathological indicators were associated with PNI positivity, such as tumor differentiation, T staging, lymph node metastasis, vascular invasion, and signet ring cell carcinoma components (P.05). PNI is an independent marker of poor prognosis in patients with gastric cancer.

Purpose: Vesicoureteral reflux (VUR) is a risk factor for various renal problems like recurrent urinary tract infections (UTIs), pyelonephritis, renal scarring, hypertension, and other renal parenchymal defects. The interventions followed by pediatricians include low-dose antibiotic treatment, surgical correction, and endoscopy. This meta-analysis aimed to assess the advantages and drawbacks of various primary VUR treatment options. Search Strategy: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of journals, and abstracts from conference proceedings were all used to find randomized controlled trials. The articles were retrieved from 1985 till 2020. Twenty articles were used for the data analysis. Criteria for Selection: Surgery, long-term antibiotic prophylaxis, noninvasive techniques, and any mix of therapies are also options for treating VUR. Collection and Interpretation of Data: Two authors searched the literature separately, determining research qualifications, assessing accuracy, and extracting and entering results. The odds ratio (OR) of these studies was used to construct the forest plot. The random-effects model was used to pool the data. Also, the random-effects model was used with statistical significance at a p value < 0.05 to assess the difference in side effects after treatment of VUR using different modalities. Results: We found no statistically significant differences between surgery plus antibiotics and antibiotic alone-treated patients in terms of recurrent UTIs (OR = 0.581; 95% confidence interval [CI] 0.259–1.30), renal parenchymal defects (OR = 1.149; 95% CI 0.75–1.754), and renal scarring (OR = 1.042; 95% CI 0.72–1.50). However, the risk of developing pyelonephritis after surgical treatment of VUR was lesser than that in the conservative approach, that is, antibiotics (OR = 0.345; 95% CI 0.126–0.946.), positive urine culture (OR = 0.617; 95% CI 0.428–0.890), and recurrent UTIs were more common in the placebo group than in the antibiotic group (p < 0.05; OR = 0.639; 95% CI 0.436–0.936) which is statistically significant. Conclusion: Based on current research, we recommend that a child with a UTI and significant VUR be treated conservatively at first, with surgical care reserved for children who have issues with antimicrobials or have clinically significant VUR that persists after several years of follow-up.

Background: The coronavirus disease 2019 (COVID-19) pandemic has posed a great challenge to the healthcare system. This study evaluated the impact of the pandemic on the utilization of primary healthcare (PHC). Methods: The outpatient data from 158 PHC institutions in Yinchuan from May 1, 2017 to April 30, 2020 were used. The difference in difference (DID) model was used to analyze the difference in the number of outpatient visits per day, total outpatient expenditure per day, and outpatient expenditure per visit between December 2019 and February 2020 compared with the same periods in two previous years. The autoregressive integrated moving average (ARIMA) modelling was used to investigate the association between the outpatient volume and the number of the last week’s new COVID-19 cases in Yinchuan, Ningxia, and China. Results: From December 2019 to February 2020, the decline in the number of outpatient visits per day (DID: -367.21 times, P=.004) was larger than that in two previous years, and a similar trend can be seen in the outpatient expenditure per day. However, the rise in the outpatient expenditure per visit (DID: 19.06 thousand yuan, P=.003) was larger than that in two previous years. In 2020, the outpatient visits for most types of diseases decreased from week 3 and rebounded after week 5. The decline and rebound of outpatient visits in the population aged 45 years and older were steeper than in those younger. The outpatient volume was negatively associated with the number of the last week’s new COVID-19 cases. Conclusion: This study indicated a significant impact of the pandemic on PHC service utilization. Since PHC service is the foundation of the healthcare system in most developing countries, measures should be taken to make PHC help cope with the crisis and relieve the burden of hospital care.

Shelterbelts, also termed windbreaks, play a significant role in reducing soil erosion, sand drift, and protecting crops, livestock and farmstead. Cropland shelterbelts are known to improve the microclimate and provide protection against sand-related damages to crops. However, the protection of shelterbelts to crops may be complicated by fine roots near the edge of the shelterbelt, which directly affects the absorption of soil water and the accumulation of soil organic carbon. In this study, we investigated the effects of shelterbelt fine roots on farmland soil water content (SWC) and soil organic carbon density in an agricultural system located in northern China. The distribution characteristics of fine-root biomass density, soil water content and soil organic carbon density were measured at the 0-200 cm soil depth in a farmland shelterbelt system at distances of 0.3H (H is the windbreak height), 0.5H, and 0.7H from the shelterbelt with three replicates. Soil samples were randomly collected in the center of the cropland. The results showed that fine roots of shelterbelts concentrated at the depth of the 20-60 cm soil layer, whereas the fine roots of the crop summer squash (Cucurbita pepo L.) were mainly found within the top 20 cm of the soil profile. With the presence of shelterbelt fine roots, strong SWC deficiency that occurred up to100 cm in the soil profile was observed. The SWC was deficient at all sampling points, the overall shallow layer deficient was larger than the deep layer. In contrast, the soil organic carbon was cumulative, and the overall deep accumulation was greater than the shallow layer. The effects of fine roots on SWC and soil organic carbon density variations in different soil layers were inconsistent. The information accrued in this study can be used to evaluate the effect of farmland shelterbelt on soil water and soil carbon in the Hetao irrigation area of Inner Mongolia, northern China.

The windbreak system is a major component of successful agricultural systems in arid deserts throughout the world. Ulan Buh Desert is one of the eight biggest deserts in China, and the oases there offer residence and cropland for over 90% of the local residents. However, due to climate change and human disturbances, the Ulan Buh Desert continues spreading to the south, bringing more pressure on the windbreak systems there. Meanwhile, the Chinese government put much effort into greening the desert, establishing artificial shrubs to prevent dune movement and soil loss. How microclimate in the cropland-windbreak-desert system responded to human activities and climate change has rarely been studied. In this study, we investigated the microclimate change dynamics across the cropland-windbreak-desert transition zone during the past 38 years. Two 50 m climatological towers, located in the same distance inner and outside a shelterbelt, have continuously monitored climatic factors, including air temperature, soil temperature, relative humidity, precipitation, evaporation, layered wind speeds, etc., and aeolian erosion related factors, such as layered dustfall. The long-time fluctuations of the inside and outside climatic factors have been analyzed, and the global climate change data, local land-use history, as well as the record of afforestation activities implemented by government and local people, were also collected. The results revealed that both the inside and outside windbreak air temperatures and soil temperatures increased during the past 38 years, which agrees with the global warming phenomenon. The inner windbreak air temperature is consistently lower than the outer windbreak areas, and the temperature difference is biggest in summer and smallest in winter. However, the soil temperature difference between the outside and inner windbreak is unstable. In 1995, 2002, and 2004, the dune areas even had lower soil temperature than the inner cropland. The precipitation is 0.5~100.7mm higher in cropland and the evaporation is lower in cropland when comparing to outside dune areas, but their annual variations changed greatly. The wind speed and erosion rate are significantly lower in cropland than desert dune areas, and the seasonal change exhibited a bimodal curve pattern. The results suggest that the cropland-windbreak-desert transition zone responded to global climate change simultaneously. Although the shelterbelt still creates a favorable regional climatic condition for the cropland, the differences between the inner and outer windbreak areas narrowed during the past 10 years. The aeolian erosion rate reduced significantly in outside windbreak dune areas, which may largely attribute to the artificial Haloxylon ammodendron communities planted at the southeastern margin of the desert.

The inappropriate selection of measurement points and measurement times in an ecosystem may easily lead to the underestimation or overestimation of soil respiration due to spatial and temporal heterogeneity. To assess the law of spatial and temporal heterogeneity and more accurately determine the soil respiration rate, we measured the soil respiration rate of a forest in the plant growing season from 2011 to 2013 on Changbai Mountain in 8 directions and 7 distances from each tree trunk. Neglecting the direction of the measuring point may overestimate or underestimate the soil respiration rate by 29.81% and 26.09%, respectively, neglecting the distance may overestimate or underestimate the soil respiration rate by 41.36% and 20.28%, respectively, and ignoring the measurement time may overestimate and underestimate the soil respiration rate by 41.71% and 57.64%, respectively. In addition, choosing a measurement point in the eastern direction at a 1.8 m distance and conducting the measurement in September may relatively accurately reflect the soil respiration rate of the ecosystem. These findings can deepen our understanding of soil respiration rate heterogeneity and may provide new ideas for improving the measurement method of soil respiration.

Water, nutrient and light deficiency during the co-growth period are the major factors limiting the productivity of the apple–maize alley cropping system in Loess Plateau, China. Therefore, it is crucial to optimize the management of water and fertilizer in the region. The effects of different irrigation and fertilizer levels on photosynthetic characteristics, growth, yield, water consumption (ET) and water use efficiency were studied in a young apple-maize intercropping system during 2014–2016. The treatments included three levels of maximum irrigation, namely 50% (W1), 65% (W2), and 85% (W3) of field capacity (Fc), and three different NPK fertilization levels (289.0-118.0-118.0, 412.4-168.8-168.8 and 537.0-219.0-219.0 kg∙ha−1), which were designated F1, F2 and F3, respectively. In addition, the rain-fed (neither irrigation nor fertilizer) crop was included as the control (CK). The F1 significantly increased the net rate of photosynthesis (Pn) and leaf water-use efficiency (LWUE) of both apple and maize. For maize, the effect of irrigation was greater than that of fertilizers on water use, but smaller on growth indicators and yield. The ET of the alley cropping systems increased with the amount of irrigation but decreased as the dose of fertilizers increased. Growth and yield of maize increased when the amount of irrigation increased, but were inversely related to fertilizer dose. The canopy architecture appeared to be regulated through differential absorption of water and nutrients. The Pn and transpiration (Tr) in maize decreased as the distance from the tree line increased, and the extent of decrease grew over time, suggesting greater interspecific competition. It is recommended that dwarf crops should be planted after intercropping for 5 years according to the change in photosynthetic index with intercropping years under different treatments. Multiple regression analysis indicated the following regime to be optimal during the first 3–5 years of the intercropping in terms of the yield of maize and water use in the alley cropping system: maximum watering (85% Fc) and minimum fertilization (289.0-118.0-118.0 kg ha−1 NPK).

In arid areas precipitation patterns and soil nutrient determine plant survival. To study the effect of fertilizer addition on plant traits and on biological soil crusts under different rainfall intervals we collected and sowed the seeds of three typical psammophyte species from a natural community in China’s Mu Us Desert, and raised their seedlings in pots. During the growing season we added commercial seaweed fertilizer to the pots and irrigated the plants at different intervals. After one growing season we measured plant traits and the biomass of biological soil crusts, and soil nutrient contents. Seaweed fertilizer increased biomass production. The combined effects of seaweed fertilizer and rainfall interval were related to the life history attributes of the species. For a given fertilizer addition, changing the rainfall interval from 3 to 15 days increased the Agriophyllum squarrosum and Achnatherum splendens biomass, but decreased Glycyrrhiza uralensis biomass. Seaweed fertilizer significantly affected plant traits, but the effects of the rainfall interval on plant traits were not significant. Fertilizer addition increased the soil organic carbon and total nitrogen. Fertilizer addition also promoted biological soil crusts and enriched their total nitrogen content. Structural equation modeling showed that the organic carbon, total nitrogen, and chlorophyll a content of the biological crusts played different roles in biomass production of the three species. Soil carbon and nitrogen affected biological soil crusts more than they affected plant biomass production. Our results show that seaweed fertilizer can promote plant growth and biological crust development, making it useful for ecosystem restoration in arid and semi-arid regions.

Amorpha fruticosa is often used to revegetate saline wasteland in the YinNan Irrigation Area, northwest China. However, the survival rate of transplanted A. fruticosa seedlings is constrained by its low tolerance to high soil salinity, drought, and low soil temperatures (Tsoil) at the early transplanting stage. This study aimed to evaluate the effects of three different mulches, including plastic mulch (PM), sand mulch (SM) and rice straw mulch (RSM), and control (CK) on the soil microenvironment and A. fruticosa seedling growth. The results indicated that PM (19.1–26.2 °C), followed by SM (18.6–26.1 °C), provided the highest Tsoil at 0–20 cm depth during the whole growing period, while RSM (16.5–21.5 °C) exhibited lower Tsoil than CK (15.8–22.0 °C) at all time except the later growing stage. RSM (7.1%–26.4%) retained soil water most effectively as compared to CK, followed by SM (3.2%–22.5%), and then PM (-0.6%–19.7%). PM (11.4%–18.5%) had the best performance in reduction of ECe at 0–80 cm depth, followed by RSM (10.5%–15.5%), and then SM (3.7%–7.4%). Still, PM exhibited the greatest improvement in soil structure. A. fruticosa seedlings grown in PM achieved the best stand establishment and growth characteristics, in which its root reached to 40–60 cm depth, while the counterparts in RSM showed the poorest performance in three mulching treatments. The results above suggest that PM is a promising strategy to promote the growth of transplanted halophytes in saline wasteland of the YinNan Irrigation Area and other areas with similar ecologies.

A field trial consisting of cotton grown employing a combination of ridge planting, mulching with film, and drip irrigation was laid out on a plot with severely saline soil in a typical inland arid area of Xinjiang. The effect of five levels of soil matric potential set up 0.2 m below the drip emitter, namely −5 kPa, −10 kPa, −15 kPa, −20 kPa, and −25 kPa, were studied in terms of changes in soil salinity (ECe), sodicity (SAR), crop growth and yield components. Drip irrigation increased the leaching of soil salts and decreased the ECe and SAR of each soil layer. Although the levels of soil salt rose again, in spring and winter, after irrigation was discontinued, the root zone (0–40 cm) remained less saline: the ECe and SAR value under the soil matric potential of −5 kPa and −10 kPa were 63% and 49% of its values in 2009 respectively, before the land was brought under cultivation (p ≤ 0.05), showing maximum leaching. The yield of cotton peaked at the soil matric potential of −5 kPa. The germination rate, which was the main factor that influenced the cotton yield, was 67% of that in non-saline soil in the first two years, and increased to 84% in the third year. After three years, the rate of germination in all the treatments exceeded 67%, and the highest rate (78%) was at −5 kPa; in the same treatment, boll yield was 4.40 g per plant. Except for germination rate and the yield of lint and seed, all the yield components increased significantly (p ≤0.05) as ECe and SAR decreased in 2010 and 2011. The correlation between soil salt (salinity and sodicity) and other components such as the number of cotton bolls per plant, the average weight of a boll, and lint percentage varied, probably because water supply was being regulated and, as a result, the physicochemical properties of the soil kept changing constantly. Taking into account the extent of leaching, crop growth, and yield, the lower limit for the soil matric potential should be −5 kPa at 20 cm below the dripper for the first three years during reclamation to promote cotton cultivation on the saline-sodic soil of Xinjiang.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree Camptotheca acuminata. CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.

BackgroundThromboembolism is a life-threatening, limb-threatening or organ-threatening complication that occurs in patients with primary nephrotic syndrome (NS). There are few studies on the spectrum, complications and outcomes of thrombosis in children with NS. This study aimed to determine the spectrum of thrombosis and its relationship with the nephrotic state, treatment and outcomes in children and adolescents with primary NS.MethodsThe medical records of subjects aged 1–18 years with NS complicated with thromboembolism treated at our centre within the last 26 years were retrieved. Data on the status of NS, site, symptoms and signs, laboratory investigations, diagnosis, treatment, complications and outcomes of thrombosis were collected and reviewed retrospectively. A severe complication was defined as a condition associated with thrombosis requiring a special diagnostic modality to confirm or a specific treatment such as surgical intervention. The outcome of thrombosis was defined as the status of thrombosis, as determined by imaging methods and the functional status with respect to the anatomic sites of thrombosis at the last follow-up. The permanent dysfunction of an organ or limb related to thrombosis was defined as a sequela.ResultsWe observed thrombosis in 1.4% (27/1995) of subjects with NS during the study period. There were 27 subjects with thrombosis, including 21 males and 6 females. Thrombosis was observed in 51.9% (14/27) of the study participants with steroid resistant NS. Most episodes of thrombosis occurred during the active stage of NS; however, 7.4% of thrombosis cases occurred during the remission of proteinuria. Renal vein thrombosis (33.3%) and pulmonary embolism (25.9%) were the most common types of thrombosis. Among the 17 subjects biopsied, minimal change disease and membranous nephropathy were the two most common findings. Six (22.2%) subjects experienced severe complications or sequelae; 1 had persistent intracranial hypertension, 1 had intestinal perforation, 1 had hypoxemia and pulmonary hypertension, 1 had lameness, 1 had epilepsy, and 1 had an askew mouth due to facial paralysis. In 19 (70.4%) subjects, the symptoms resolved completely or improved without severe complications or sequelae.ConclusionsThrombosis mostly occurred in males of school age during the active stage of NS. Renal vein thrombosis and pulmonary embolism were the most common types of thrombosis. In most patients with thrombosis, the symptoms improved completely without complications with standard anticoagulation therapy. However, 22.2% had severe complications or sequelae requiring an advanced diagnostic modality and aggressive treatment.

Background: A false interpretation of homozygosity for pathogenic variants causing autosomal recessive disorders can lead to improper genetic counseling. The aim of this study was to demonstrate the underlying etiologies of presumed homozygous disease-causing variants harbored in six unrelated children with five different genetic renal diseases when the same variant was identified in a heterozygous state in only one of the two parents from each family using direct sequencing. Methods: Peripheral blood genomic DNA samples were extracted. Six short tandem repeats were used to verify the biological relationships between the probands and their parents. Quantitative PCR was performed to detect mutant exons with deletions. Single nucleotide polymorphism analysis and genotyping with polymorphic microsatellite markers were performed to identify uniparental disomy (UPD). Results: Each proband and his/her parents had biological relationships. Patients 2, 4, and 6 were characterized by large deletions encompassing a missense/small deletion in DGKE, NPHP1, and NPHS1, respectively. Patients 1 and 5 were caused by segmental UPD in NPHS2 and SMARCAL1, respectively. In patient 6, maternal UPD, mosaicism in paternal sperm or de novo variant in NPHP1 could not be ruled out. Conclusions: When a variant analysis report shows that a patient of non-consanguineous parents has a pathogenic presumed homozygous variant, we should remember the need to assess real homozygosity for the variant, and a segregation analysis of the variants within the parental DNAs and comprehensive molecular tests to evaluate the potential molecular etiologies, such as a point variant and an overlapping exon deletion, UPD, germline mosaicism and de novo variant, are crucial.

Pediatric native kidney diseases are common worldwide. The pathological diagnosis of kidney lesions is crucial for clinical treatment and prognosis. The aim of the current study was therefore to evaluate the value of electron microscopy (EM) to the final diagnosis of native kidney biopsies in children.A retrospective evaluation of 855 pediatric kidney biopsies obtained from the Department of Pediatrics in Peking University First Hospital between November 2010 and December 2017 was performed to assess the contribution of EM to the final diagnosis.The role of EM in the final diagnosis was determined to be crucial in 300 cases (35.1%), important in 280 cases (32.7%), and auxiliary in 275 cases (32.2%). EM is considered most valuable in a large percentage of glomerular diseases, mainly including minimal change disease, early-stage membranous nephropathy, postinfectious glomerulonephritis, Alport syndrome, thin basement membrane nephropathy, and thrombotic microangiopathy. EM also provided helpful diagnostic information in cases of focal segmental glomerulosclerosis, lupus nephritis, IgA nephropathy, and IgA vasculitis (Henoch-Schonlein purpura nephritis). Additionally, EM was crucial in 90.0% of cases of subtle pathological changes observed with light microscopy (LM) and immunofluorescence (IF) and in 69.3% of the IF-negative specimens. Patients with nephrotic syndrome or hematuria also benefit from ultrastructural examination.The present study demonstrated the crucial or important role of EM in the diagnosis of a majority of native kidney biopsies in children. The application of EM should be integrated together with LM and IF as a routine method of assessing pediatric kidney specimens. Graphical abstract.

Background To characterize the phenotypic spectrum and assess the antialbuminuric response to angiotensin converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) therapy in a cohort of children with Dent disease. Methods The patients’ clinical findings, renal biopsy results, genetic and follow‐up data were analyzed retrospectively. Mutations in CLCN5 or OCRL were detected by next‐generation sequencing or Sanger sequencing. Results Of 31 Dent disease boys, 24 carried CLCN5 and 7 carried OCRL mutations. Low molecular weight proteinuria and albuminuria were detected in all cases. Nephrotic‐range proteinuria and severe albuminuria were identified in 52% and 62% of cases, respectively; by 7 years of age, 6 patients had hematuria and nephrotic‐range proteinuria, and 7 patients had hematuria and moderate to severe albuminuria. In addition to disease‐related renal features, patients with Dent‐1 disease also presented with congenital cataract (1/9) and developmental delay (2/7). Seventeen of 31 patients underwent renal biopsy. Glomerular changes included mild glomerular lesions, mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Thirteen of the 31 patients had follow‐up records and received ACE inhibitor and/or ARB treatment for more than 3 months. After a median 1.7 (range 0.3–8.5) years of treatment, a reduction in the urinary microalbumin‐to‐creatinine ratio was observed in 54% of children. Conclusions Hematuria with nephrotic‐range proteinuria or moderate to severe albuminuria was common in Dent disease patients. Extrarenal manifestations were observed in Dent‐1 patients, which extends the phenotypic spectrum. In addition, ACE inhibitors and ARBs are well tolerated, and they are partially effective in controlling albuminuria., Hematuria with nephrotic‐range proteinuria or moderate to severe albuminuria was common in Dent disease patients.Patients with Dent‐1 disease may also present with congenital cataract and developmental delay.The percentage of urinary albumin in the total protein ranged from 24.2% to 47.6%; it was usually smaller than that of LMW proteinuria. ACE inhibitors and ARBs are partially effective in controlling albuminuria and they are well tolerated.

Alport syndrome is a hereditary progressive chronic kidney disease caused by mutations in type IV collagen genes COL4A3/4/5. X-linked Alport syndrome (XLAS) is caused by mutations in the COL4A5 gene and is the most common form of Alport syndrome. A strong correlation between the type of COL4A5 mutation and the age developing end-stage renal disease in male patients has been found. Mutation to the α (IV) chain causes retention of the protein to the endoplasmic reticulum lumen, which causes endoplasmic reticulum stress (ERS) and subsequent exertion of deleterious intracellular effects through the activation of ERS. The exact time point that mutant type IV collagen α chain exerts its deleterious effects remains elusive. In this study, we explored the relationship between the COL4A5 genotype and cell type in ERS activation. We obtained skin fibroblasts from Alport syndrome patients with different COL4A5 mutation categories [i.e., a missense mutation (c.4298G > T, p.Gly1433Val) in exon 47, a splicing mutation (c.1949–1G > A) in intron 25 and an insertion (c.573_c.574insG, p. Pro193Alafs*23) in exon 10], and then reprogrammed these fibroblasts into induced pluripotent stem cells (iPSCs). Interestingly, no significant dysregulation of ERS pathway markers was observed for the three COL4A5 mutant iPSCs; however, significant activation of ERS in COL4A5 mutant fibroblasts was observed. In addition, we found that the activation levels of some ERS markers in fibroblasts varied among the three COL4A5 mutation types. Mutant COL4A5 proteins were demonstrated to have different effects on cells at different stages of ontogenesis, providing a theoretical basis for choosing the timing of intervention. The observed differences in activation of ERS by the COL4A5 mutant fibroblasts may contribute to the intracellular molecular mechanisms that describe the correlation between genotype and clinical features in XLAS.

Background Alport syndrome is a rare hereditary kidney disease manifested with progressive renal failure. Considerable variation exists in terms of disease progression among patients with Alport syndrome. Identification of patients at high risk of rapid progression remains an unmet need. Urinary epidermal growth factor (uEGF) has been shown to be independently associated with risk of progression to adverse kidney outcome in multiple independent adult chronic kidney disease (CKD) cohorts. In this study, we aim to assess if uEGF is associated with kidney impairment and its prognostic value for children with Alport syndrome. Methods One hundred and seventeen pediatric patients with Alport syndrome and 146 healthy children (3–18 years old) were included in this study. uEGF was measured in duplicates in baseline urine samples using ELISA (R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients with longitudinal follow-up data (n = 38), progression was defined as deteriorated kidney function (CKD stage increase) during follow-up period (follow-up length is about 31 months in average). The association of baseline uEGF/Cr level with estimated glomerular filtration rate (eGFR) slope and Alport syndrome patients’ progression to a more advanced CKD stage during the follow-up period was used to evaluate the prognostic value of the marker. Results We found that uEGF/creatinine (uEGF/Cr) decreases with age in pediatric patients with Alport syndrome with a significantly faster rate than in healthy children of the same age group. uEGF/Cr is significantly correlated with eGFR (r = 0.75, p

Aim The TTC21B gene is now known as causative of nephronophthisis-related ciliopathies (NPHP-RC). We reported two Chinese pediatric cases with end-stage renal disease and other phenotypes caused by the TTC21B gene mutations. Methods The clinical features of Chinese pediatric cases with NPHP-RC were summarized. Mutation analysis of the TTC21B gene was performed using next-generation sequencing. Results The two cases both had nephrotic proteinuria, renal failure, hypertension and abnormal liver function (or hepatic fibrosis). One case also presented situs inversus and short phalanges. They developed end-stage renal disease (ESRD) at 1 year old and 8 years old, respectively, when renal pathology both showed focal segmental glomerular sclerosis (FSGS) with tubulointerstitial lesions including interstitial fibrosis and atrophic tubules. Three novel disease-causing TTC21B mutations were identified. One case carried homozygous mutation c.2211 + 3A > G, while the other case carried compound heterozygous mutations c.1552 T > C (p.C518R) and c.1456dupA (p.R486KfsX22). Conclusion Mutations in TTC21B cause a range of ciliopathy phenotypes in humans. We identified 3 novel TTC21B mutations in two Chinese pediatric cases that both presented end-stage renal disease and other different features. This is the first TTC21B mutations ever reported in China.

Ecological restoration by Tamarix plants on semi-arid saline lands affects the accumulation, distribution patterns and related mechanisms of soil water content and salinity. In this study, spatio-temporal variations of soil water content and salinity around natural individual Tamarix ramosissima Ledeb. were invetigated in a semi-arid saline region of the upper Yellow River, Northwest China. Specifically, soil water content, electrical conductivity (ECe), sodium adsorption ratio (SARe), and salt ions (including Na+, K+, Ca2+, Mg2+ and SO42–) were measured at different soil depths and at different distances from the trunk of T. ramosissima in May, July, and September 2016. The soil water content at the 20–80 cm depth was significantly lower in July and September than in May, indicating that T. ramosissima plants absorb a large amount of water through the roots during the growing period, leading to the decreasing of soil water content in the deep soil layer. At the 0–20 cm depth, there was a salt island effect around individual T. ramosissima, and the ECe differed significantly inside and outside the canopy of T. ramosissima in May and July. Salt bioaccumulation and stemflow were two major contributing factors to this difference. The SARe at the 0–20 cm depth was significantly different inside and outside the canopy of T. ramosissima in the three sampling months. The values of SARe at the 60–80 cm depth in May and July were significantly higher than those at the 0–60 cm depth and higher than that at the corresponding depth in September. The distribution of Na+ in the soil was similar to that of the SARe, while the concentrations of K+, Ca2+, and Mg2+ showed significant differences among the sampling months and soil depths. Both season and soil depth had highly significant effects on soil water content, ECe and SARe, whereas distance from the trunk of T. ramosissima only significantly affected ECe. Based on these results, we recommend co-planting of shallow-rooted salt-tolerant species near the Tamarix plants and avoiding planting herbaceous plants inside the canopy of T. ramosissima for afforestation in this semi-arid saline region. The results of this study may provide a reference for appropriate restoration in the semi-arid saline regions of the upper Yellow River.

Accurate assessments of soil organic carbon (SOC) and total nitrogen (TN) stocks and controlling factors are essential for understanding carbon and nitrogen sequestration in soil. In this study, we analyzed the spatial distribution and influencing factors of SOC and TN stocks to the depth of 3 m in a desert oasis ecotone of northwestern China. The study area has experienced large-scale transition of dunelands to irrigated croplands in the past 40–50 years. The results showed that the vertical distributions of SOC and TN stocks were well demonstrated by quadratic function forms. The SOC and TN stocks at 0–3 m depths in nabkha dunes were generally significantly higher than that in bare sand dunes. Additionally, after converting nabkha dunes to croplands, both SOC and TN stocks at the top 0.4 m depths increased with the extension of cultivation years, the mean SOC and TN stocks significantly increased from 0.396 to 0.992 kg·m−2 and from 0.053 to 0.096 kg·m−2, respectively. The strongest heterogeneity of SOC and TN generally appeared at top 0–0.4 m depths and decreased with the depth. The SOC and TN stocks in the nabkha dunes near the water areas were relatively higher, which may be suitable for croplands reclamation. It is noteworthy that land use brought a major influence of SOC and TN at top 0–0.4 m depths, whereas soil texture (clay and silt contents) was the main factor that controlled SOC and TN at deep soil depths (1–3 m). The results indicate that the nabkha dunes also increased carbon and nitrogen stocks throughout the entire 3 m soil profiles. While the demand for food is almost certain to increase in arid and semiarid China and other regions worldwide, the conversion from non-traditional croplands such as dunelands to croplands is likely going to continue.

The widely used International Study of Kidney Disease in Children (ISKDC) classification for Henoch-Schonlein purpura nephritis (HSPN) does not completely correlate with the clinical presentation and long-term prognosis of this disease. Primary IgA nephropathy (IgAN) and HSPN share common features; thus, the Oxford classification of IgAN might be useful in predicting the long-term outcomes of HSPN. However, its value has not been confirmed in children with HSPN. We selected children with HSPN diagnosed between 2003 and 2015, and reclassified their renal biopsies according to the Oxford classification scoring system. The primary outcome was impaired renal function, and remission of proteinuria and clinical remission were secondary outcomes. We included 104 patients (58 males, 46 females) with a median age of 10 (4–17) years. Mesangial hypercellularity (M1) was strongly associated with proteinuria, and tubular atrophy/interstitial fibrosis (T1&2) and C2 (with crescents in > 25% of glomeruli) were associated with reduced estimated glomerular filtration rate (eGFR) at the time of biopsy. Patients with M1, endocapillary proliferation (E1), segmental glomerulosclerosis (S1), and crescents (C1&2) were more likely to have been treated with high-dose methylprednisolone. At univariate time-dependent analyses, S1 was strongly associated with the primary outcome (p = 0.025), whereas T1&2 was significantly negatively associated with proteinuria remission (p = 0.035) and clinical remission (p = 0.038). Our findings suggest that the Oxford classification is valid for children with HSPN. S and T lesions, which are ignored in the ISKDC classification, can be used to assess renal outcomes of HSPN, and such assessments are not affected by currently available treatments. The value of M, E and C lesions in predicting response to therapy and renal outcome warrants further study.

The loess plateau of northern China has always been severely affected by drought and rainfall, impacting ecological integrity and sustainable development in particular. Super-absorbent polymers (SAPs) can relieve the pressure of water shortages and change the process of rainfall-runoff. In this study, SAPs were mixed with soil in percentages(weight ratio) of 0, 0.25%, 0.5%, 0.75%, 1% and 2%; then, these mixtures were applied in 5 cm depth layers in runoff plots of 5 m × 4 m for every treatment (T1, T2, T3, T4, T5). Artificial rainfall intensity was controlled at 40 mm/h, and the rainfall duration was 0.5 h when the soil physical and chemical properties were surveyed. With SAPs, the initial runoff time of different treatments increased by 21.5-102.7%; the amount of surface runoff decreased remarkably; the SAPs could reduce the loss of soil and water: the runoff reduction effect was 24.6% (T1), 41.5% (T2), 46.5% (T3), 50.7% (T4), and 60.6% (T5); the sediment reduction effect was very significant at 58.8% (T1), 74.1% (T2), 85.6% (T3), 80.9% (T4), and 75% (T5); and the lowest losses of total nitrogen (TN 0.09 kg), total phosphorus (TP 5.02 g) and total potassium (TK 0.08 kg) were measured in T3,with 14.9%, 14.2% and 13.1% that of the control (CK), respectively. The soil moisture content increased by 19.2%, 32.5%, 33.5% and 31.3% compared to CK in the different soil layers; SAPs could raise the soil temperature by 0.72 °C (T5) and lower the soil temperature by 0.53 °C (T5) in September and July, respectively. The aboveground biomass and underground biomass of the treatments increased by a maximum value of 84.4% in T3, which was 38% greater than CK, and the vegetation in T3 (44 kinds) was the most abundant and it was 69.2% more than CK (26 kinds). The effect was not always positively correlated with the percentage of SAPs. The application of SAPs in this study showed a comprehensive utility (soil erosion prevention, redistribution of soil water and temperature, maintenance of fertility and the synergy between SAPs and plants), which suggest that the most basic goal, to ensure socio-economic and ecological sustainability in dryland systems, is obtained.

The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity.Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome.A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome.Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.

Dent disease is an X-linked recessive proximal tubular disorder that affects mostly male patients in childhood or early adult life, caused by mutations in CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes, respectively. It presents mainly with hypercalciuria, low-molecular-weight proteinuria, nephrocalcinosis and progressive renal failure. We report here the same CLCN5 mutation but different phenotypes in two Chinese brothers, and speculate on the possible reasons for the variability of the genotype-phenotype correlations.

Hereditary nephrotic syndrome often presents with steroid-resistance and onset within the first year of life. Mutations in genes highly expressed in podocytes have been found in two thirds of these patients, especially NPHS1 and NPHS2 among at least 29 genetic causes that have been discovered. We reported two siblings with steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at NPHS1 (c.1339G>A, p.E447K) and ACDK4 (c.748G>C, p.D250H) genes. The siblings presented with steroid-resistant nephrotic syndrome and pathological lesions of focal segmental glomerulosclerosis (FSGS), while the elder sister also developed hypertension, renal failure and cardiac dysfunction.

Postsurgical relapse remains a common issue for resectable gastric cancer (GC). Here, we investigated the efficacy and safety of an adjuvant treatment combining chemotherapy with cellular immunotherapy (CIT) using autologous natural killer cells, γδT cells, and cytokine‐induced killer cells in the treatment of stage II/III GC. A pilot prospective cohort study was conducted in 169 patients with stage II/III GC who had undergone gastrectomy with D2 lymph node dissection. Patients were assigned into two groups according to the patient choice of treatment, including chemotherapy alone (chemo) or chemotherapy combined with CIT (chemo/CIT). Disease‐free survival (DFS), overall survival (OS), and adverse events were evaluated. Univariate and multivariate Cox models were used to analyze the impact of chemo/CIT on DFS and OS. Kaplan–Meier analysis with the log‐rank test was used to compare the clinical outcome between two groups. Three‐year DFS rate was 60.6% and 74.7% (P = 0.036) and 3‐year OS rate was 64.9% and 83% (P = 0.051) for the chemo and chemo/CIT group, respectively. TNM stage and chemo/CIT were independent prognostic factors for both DFS (for TNM stage, P

Background The aim of this study was to analyze the diverse phenotypes of children with PAX2‐related disorder so as to improve our understanding of this disease. Methods The clinical data of ten children with PAX2 mutations, detected by targeted region capture sequencing or whole‐exome sequencing, were retrospectively analyzed. Family members of index cases were verified by Sanger sequencing and family segregation analysis was performed. Results The age of first symptom of 10 unrelated children (six girls and four boys) was 6.4 (ranged from postnatal day to 14.8) years old. Proteinuria, abnormal renal function, and structure were found in all patients. Renal hypoplasia and renal cysts were found in 10 of 10 and five of 10 cases, respectively. Three patients progressed to chronic kidney disease stage 5 and the onset age of end‐stage renal disease was 9.8–16.4 years old. PAX2‐related ocular abnormalities were found in five of seven cases and three patients were observed to have more than one ocular findings involved. In addition to diverse renal and ocular findings, new phenotypes including congenital ventricular septal defect, skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and relatively rare extrarenal manifestations such as growth retardation, gout, and microcephaly were also found. Three novel mutations were reported for the first time. De novo mutations occurred in all patients who were carried out segregation analysis. Patients with the same mutation had different manifestations. PAX2‐related disorder showed remarkable clinical variability and phenotypic heterogeneity. Conclusion We firstly reported skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and congenital ventricular septal defect as new phenotypes of PAX2‐related disorder which enlarged the phenotypic spectrum. Gout was firstly reported as the onset symptom of PAX2‐related disorder. The diagnosis of PAX2‐related disorder should be considered without family history due to a much higher percentage of De novo mutations.

Background The main issue of this study is to demonstrate whether M-phase phosphoprotein 8 (MPP8) affect gastric tumor growth and metastasis. Methods Retrospective study was proceeded in 280 patients' surgical specimens with different disease stages. Loss-of-function assays, including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, flow cytometry, and transwell assays were performed to evaluate the biological function of MPP8 in gastric cancer cells. Apoptosis and metastasis relative biomarkers were measured by quantitative real-time polymerase chain reaction and Western blot analysis. Results Compared with normal adjacent tissues, obviously elevated MPP8 expression was found in gastric cancer tissues. Elevated MPP8 expression was associated with male sex (vs female sex), intermediate differentiation (vs poorly differentiated cancer), and later stage (vs earlier stage). Furthermore, MPP8 overexpression in tumor tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased apoptosis-related proteins (p53, Bax, and PARP) expression, but downregulated Bcl-2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway-related proteins (N-cadherin and vimentin), and as well as the levels of anti-oncogene ZEB1, MET, and KRAS mRNA. Conclusion Our findings demonstrated that MPP8 might be an oncogene by positively regulating gastric cancer cell function through the p53/Bcl-2 and epithelial to mesenchymal transition-related signaling pathways.

Background Alport syndrome is an inherited renal disease caused by mutations in COL4A3, COL4A4, or COL4A5 genes. Coexisting mutations in either two of the three genes in Alport patients have been reported recently. However, the effect of heterozygous mutations in COL4A3 or COL4A4 genes in X‐linked Alport syndrome (XLAS) patients is unclear. Methods Using targeted next‐generation sequencing, six unrelated Chinese children were identified to have a combination of a pathogenic variant in COL4A5 and a heterozygous mutation in COL4A3 or COL4A4. They were three males and three females. Another three XLAS males each with only one pathogenic variant in COL4A5 were included. The clinical data were analyzed and compared between the males in two groups (group 1, males with a pathogenic variant in COL4A5 and a heterozygous pathogenic variant in COL4A3 or COL4A4; group 2, males with only one pathogenic variant in COL4A5). Results Patients with XLAS who also had heterozygous pathogenic COL4A3 or COL4A4 variants accounted for 1% of Alport syndrome. In this study, three children showed coexisting pathogenic variants in COL4A5 and COL4A3. Two children showed pathogenic variants in COL4A5 and COL4A4. One child had pathogenic variants in the three COL4A3‐5 genes, in which the pathogenic variant in COL4A5 was de novo and the pathogenic variants in COL4A4 and COL4A3 were inherited independently (in trans). The site and type of mutations in COL4A5 were similar between the two groups. It was revealed that males in group 1 presented more severe proteinuria than males in group 2 (p

Objectives The aims of this study were to investigate the population pharmacokinetic (PPK) characteristics of tacrolimus in Chinese children with nephrotic syndrome and to apply it in clinical practice. Materials and methods A total of 137 concentrations from 61 patients were collected from routine therapeutic drug monitoring data between 2011 and 2018. Population modeling was performed with the nonlinear mixed-effects model (NONMEM) program, using a one-compartment model with first-order absorption and elimination. The mean population estimate values of clearance (CL/F) and volume of distribution (V/F) were determined. Common demographic and clinical variables were tested for their influence on these parameters. External validation was conducted, and Monte Carlo simulation, based on the final model, was carried out to determine optimal dosage regimen. Results Age and body weight were the covariates that displayed a significant influence on CL/F and V/F according to the final regression model. Goodness-of-fit plots, bootstrap outcomes, and external validation confirmed the relatively good stability and prediction capability of the model. The interindividual variability of CL/F was 31.10%, and the residual variability was 0.91 ng/mL. Mean prediction error (MPE, %) and Mean absolute prediction error (MAPE, %) were 10.3% and 16.6%, respectively. Monte Carlo simulation based on the final model was carried out to determine optimal dosage regimen. Conclusion A PPK model of tacrolimus in children with nephrotic syndrome was developed. Age and bodyweight could partly explain the interindividual variability in the CL/F and V/F of tacrolimus. The final model could be used to accurately predict tacrolimus individual pharmacokinetic parameters and assist in dosage optimization. .

为了试用figshare上传的半成品数据

为了试用figshare上传的半成品数据

为了试用figshare上传的半成品数据

Tamarisk (Tamarix ramosissima) plants are widely distributed in semi-arid regions with saline soils. In these environments, the survival and sustainability of the Tamarisk plants are critically related to the availability and distribution of soil water and salt. In this study, we analyzed the soil water content (SWC) and soil electrical conductivity (EC) to the depth of 60 cm in natural Tamarisk communities, located in a semi-arid saline region of northwestern China, in July 2016 (a normal period) and July 2017 (a dry period). The results showed that SWC varied from 1.91 to 7.82% and soil EC ranged from 9.65 to 25.38 mS/cm in the 0–60 cm soil layer. Despite the deficiency of precipitation in the study period of 2017, the SWC in all plots was higher at the 20–60 cm depth than that of the normal study period in 2016. Compared to 2016, the soil was also less saline in 2017, representatively by lower soil EC values at the 0–40 cm depth. Additionally, the SWC decreased with Tamarisk density, indicating that Tamarisk plants increase water consumption. The SWC and soil EC both revealed “island” distribution, with highest level found inside or underneath the Tamarisk plant canopies. Both the SWC and soil EC presented a strong or moderate spatial dependency, and the spatial dependency in soil EC were significantly affected by community composition. Correlations (Pearson’s r) showed that there were positive correlations between SWC and soil EC. The results above indicate that Tamarisk communities can ameliorate the semi-arid high saline soil environment, and that the growth and distribution of Tamarisk plants influence the spatiotemporal variability of SWC and soil EC. In addition, the results also demonstrate that the possible appropriate density in the process of constructing Tamarisk plants should be considered in order to achieve the optimal water condition. The study may provide a scientific basis for the ecological restoration and halophytes establishment in the semi-arid saline region of northwestern China and other areas with similar ecologies.

Dent's disease is an X-linked recessive proximal tubular disorder that mostly affects male patients in childhood or early adult life. The condition is caused by mutations in the CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes located on chromosome Xp11.22 and Xq25, respectively. In most male patients, proteinuria is subnephrotic but may reach nephrotic levels. Here, we report the first case of Dent's disease complicated by nephrotic syndrome. Dent's disease should be considered in the differential diagnosis of nephrotic syndrome, and especially in male patients with early onset of nephrotic syndrome. A urinary α1-microglobulin/albumin ratio > 1 may provide the first clue to a tubulopathy.

Background The main issue of this study is to demonstrate whether M-phase phosphoprotein 8 (MPP8) affect gastric tumour growth and metastasis. Methods Retrospective study was proceeded in 280 patients’ surgical specimens with different disease stages. Lentivirus delivery of short hairpin RNA targeting MPP8 was also used to explore the function of MPP8 in gastric cancer cells. Quantitative real-time PCR and western blot were applied to measure apoptosis and metastasis relative biomarker. Results The present study revealed that MPP8 expression was higher in surgical specimens from patients with gastric cancer (vs. normal adjacent tissues), and that elevated expression was associated with male sex (vs. female sex), intermediate differentiation (vs. poorly differentiated cancer), and later stage (vs. earlier stage). Furthermore, MPP8 overexpression in tumour tissues was marginally associated with a poor prognosis, with a significant relationship between MPP8 overexpression and prognosis among patients with poorly differentiated gastric cancer. Inhibition of MPP8 in these cells significantly suppressed proliferation and colony formation, promoted apoptosis, and repressed invasion. Furthermore, silencing of MPP8 remarkably increased the expression of apoptosis-related proteins (p53, Bax, and PARP), and down-regulated Bcl-2 expression. Silencing of MPP8 also decreased the expression of metastasis pathway-related proteins (N-cadherin and vimentin), and as well as the levels of anti-oncogene ZEB1, MET, and KRAS mRNA. Conclusions These results suggest that MPP8 plays a critical role in regulating gastric cancer apoptosis and metastasis via the p53/Bcl-2 and EMT-related signalling pathways, respectively, which may indicate that MPP8 is a promising target for treating gastric cancer. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Low-molecular-weight proteinuria is one of the characteristic clinical manifestations of renal tubular and interstitial diseases. Low-molecular-weight proteinuria is defined as excessive urinary loss of α1-microglobulin, β2-microglobulin, or other low-molecular-weight plasma proteins. The current study examined the ratio of urinary α1-microglobulin to microalbumin in 24 Chinese pediatric patients with renal tubular and interstitial diseases, including 10 patients with Dent disease, 2 patients with Lowe syndrome, 6 patients with acute tubulointerstitial nephritis (ATIN), 4 patients with acute tubulointerstitial nephritis with uveitis syndrome (TINU), and 2 patients with nephronophthisis (NPHP). Patients with steroid-sensitive nephrotic syndrome, IgA nephropathy, Henoch-Schonlein purpura nephritis, or lupus nephritis served as control groups. In all of the patients with tubular and interstitial disease, urinary α1-microglobin increased 10-300-fold above the upper limit of the normal range, the ratio of urinary α1-microglobulin to microalbumin was greater than 1, and the percentage of low-molecular-weight plasma proteins (LMWP) in urine was greater than 50% according to urine protein electrophoresis. There was close correlation between the ratio of urinary α1-microglobulin to microalbumin and the percentage of LMWP in urine according to urine protein electrophoresis (r = 0.797, p = 0.000). We suggested firstly that the ratio of urinary α1-microglobulin to microalbumin, greater than 1, can be used as a diagnostic criterion for tubuloproteinuria.

Hereditary nephrotic syndrome often presents with steroid-resistance and onset within the first year of life. Mutations in genes highly expressed in podocytes have been found in two thirds of these patients, especially NPHS1 and NPHS2 among at least 29 genetic causes that have been discovered. We reported two siblings with steroid-resistant nephrotic syndrome caused by co-inheritance of mutations at NPHS1 (c.1339G>A, p.E447K) and ACDK4 (c.748G>C, p.D250H) genes. The siblings presented with steroid-resistant nephrotic syndrome and pathological lesions of focal segmental glomerulosclerosis (FSGS), while the elder sister also developed hypertension, renal failure and cardiac dysfunction.

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients. Thirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1–4, SCR 7, SCRs 11–14, and SCRs 19–20). Purified IgG from plasma from seven patients were used for functional analyses. All patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19–20 domains of CFH but not the SCRs 1–4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells. Our study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.

The aim of this study was to analyze the long-term efficacy and safety of angiotensin-converting enzyme inhibitor (ACEi) and ACEi + angiotensin receptor blocker (ARB) treatments in a cohort of children with Alport syndrome (AS). This was a respective review of 79 Chinese children with AS who received ACEi alone or combined ACEi + ARB therapy. The mean age of the pediatric patients with AS at onset of treatment was 8.6 ± 4.1 (range 1.5–16.3) years. The mean duration of follow-up was 2.5 ± 1.8 (range 0.5–7.8) years. For analysis, we separated the children into three groups according to proteinuria level before treatment, namely

Dent disease is a rare X-linked recessive proximal tubular disorder that affects mostly male patients in childhood or early adult life. Dent disease is clinically characterized by the presence of low molecular weight proteinuria (LMWP), hypercalciuria, medullary nephrocalcinosis, nephrolithiasis, and progressive renal failure. The clinical features, diagnosis, and treatment of Dent disease were examined in 10 Chinese boys. All 10 childhood cases of Dent disease in China presented with tubular proteinuria in the nephrotic range and hypercalciuria. The ratio of α1-microglobulinuria to microalbuminuria, if close to or above 1, can be used as a diagnostic criterion for tubuloproteinuria. Lotensin was ineffective at treating proteinuria while dihydrochlorothiazide reduced urine calcium excretion.

The TTC21B gene is now known as causative of nephronophthisis-related ciliopathies (NPHP-RC). We reported two Chinese paediatric cases with end-stage renal disease and other phenotypes caused by the TTC21B gene mutations.The clinical features of Chinese paediatric cases with NPHP-RC were summarized. Mutation analysis of the TTC21B gene was performed using next-generation sequencing.The two cases both had nephrotic proteinuria, renal failure, hypertension and abnormal liver function (or hepatic fibrosis). One case also presented situs inversus and short phalanges. They developed end-stage renal disease (ESRD) at 1 year old and 8 years old, respectively, when renal pathology both showed focal segmental glomerular sclerosis (FSGS) with tubulointerstitial lesions including interstitial fibrosis and atrophic tubules. Three novel disease-causing TTC21B mutations were identified. One case carried homozygous mutation c.2211 + 3A G, while the other case carried compound heterozygous mutations c.1552 T C (p.C518R) and c.1456dupA (p.R486KfsX22).Mutations in TTC21B cause a range of ciliopathy phenotypes in humans. We identified 3 novel TTC21B mutations in two Chinese paediatric cases that both presented end-stage renal disease and other different features. This is the first TTC21B mutations ever reported in China.

A core cross-linked polymeric micellar cisplatin(IV) conjugate prodrug is prepared by attaching the cisplatin(IV) to mPEG-b-PLL biodegradable copolymers to form micellar nanoparticles that can disintegrate to release the active anticancer agent cisplatin(II) in a mild reducing environment. Moreover, in vitro studies show that this cisplatin(IV) conjugate prodrug displays enhanced cytotoxicity against HepG2 cancer cells compared with cisplatin(II). Further studies demonstrate that the high cellular uptake and platinum-DNA adduct of this cisplatin(IV) conjugate prodrug can induce more cancer-cell apoptosis than cisplatin(II), which is responsible for its enhanced anticancer activity.