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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 < 0.001, hazard ratio [HR]: 5.599, 95% confidence interval [CI]: 2.791-11.232; for chemo/CIT, P = 0.013, HR: 0.478, 95% CI: 0.266-0.858) and OS (for TNM stage, P < 0.001, HR: 6.559, 95% CI: 2.903-14.817; for chemo/CIT, P = 0.04, HR: 0.506, 95% CI: 0.264-0.970). In subgroup analysis, 3-year DFS and OS rates of patients with stage III GC in the chemo/CIT group were significantly higher than those in the chemo group (38.4% vs. 57.1%, P = 0.038; and 45.9% vs. 76%, P = 0.06, respectively), while there was no significant difference between the two groups in patients with stage II GC. Only 15.9% of patients (10/63) in the chemo/CIT group had mild and manageable fever (grades 1 and 2), while no other side effects were observed. The adjuvant treatment combining chemotherapy with cellular immunotherapy is well tolerated and significantly improves the clinical outcome of patients with stage II/III GC, when compared with chemotherapy alone, therefore warrants further attention in treatment for relapsed GC after tumor resection. [ABSTRACT FROM AUTHOR]

Defects in the mitochondrial tRNA genes cause a group of highly clinically and genetically heterogeneous disorders, which poses a challenge for clinical identification and genetic diagnosis. Here, we present a pre‐school boy with a novel MT‐TD variant m.7560T>C at the heteroplasmy level of 76.53% in blood, 93.34% in urine sediments, and absent in the healthy mother's blood and urine. Besides convulsions, brain magnetic resonance imaging abnormalities and high plasma lactate, the boy presented with the prominent extra‐neurologic phenotype including steroid‐resistant nephrotic syndrome associated with focal segmental glomerulosclerosis characterized by abnormal mitochondria in podocytes, cortical blindness, and pancreatitis. To our knowledge, this is the unique case with MT‐TD m.7560T>C‐related multi‐organ impairments, which expands the phenotypic and mutational spectrum of primary mitochondrial diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.05). Conclusion: The present study provides further evidence for complicated genotype in Alport syndrome. For the first time, we reported a case with three pathogenic variants in COL4A5, COL4A3, and COL4A4 genes. Moreover, we found that heterozygous pathogenic COL4A3 or COL4A4 variants are likely to make XLAS disease more serious. [ABSTRACT FROM AUTHOR]

Objective: To explore the genetic etiology and clinical outcome of a child with co-morbid progressive IgA nephropathy and COQ8B-associated glomerulopathy., Methods: A child who was admitted to Peking University First Hospital on March 2, 2021 was selected as the study subject. Genomic DNA was extracted from peripheral blood samples from the child and his parents and sister. Whole exome sequencing was carried out, and candidate variant was verified by Sanger sequencing. This study was approved by the Peking University First Hospital (Ethics No. 2016[1029])., Results: The child, a 7-year-old boy who had developed proteinuria 8 months before, was diagnosed with IgA nephropathy (M1E1S1T1C1). With steroid, cyclophosphamide, cyclosporine and angiotensin-converting enzyme inhibitor therapy, partial remission of proteinuria was achieved. However, his serum creatinine level had increased from 53.8 mol/L at the onset of disease to 86.7 mol/L after 3.9 years, along with massive proteinuria. Kidney biopsy still indicated IgA nephropathy (M0E0S1T0C0). The child was found to harbor a homozygous c.737G>A (p.Ser246Asn) missense variant of the COQ8B gene, for which his parents and sister were heterozygous carriers. The variant was predicted to be pathogenic (PS1+PM2&#95;Supporting+PM3+PP3+PP4) based on the guidelines from the American College of Medical Genetics and Genomics. The child was treated with high-dose coenzyme Q10 in combination with steroid and/or mycophenolate mofetil, though his serum creatinine level still increased to 286 mol/L after 7.3 years, which conformed to a chronic kidney disorder with glomerular filtration rate category of G3b., Conclusion: The homozygous c.737G>A missense variants of the COQ8B gene probably underlay the progressive kidney dysfunction in this child. For children with IgA nephropathy presenting with atypical clinical manifestations, unsatisfactory therapeutic effect, and/or early onset of kidney function decline, coexistence of other diseases should be suspected.

Background: Vacuum packaging has the ability to reduce oxidative deterioration and microbial-induced spoilage of meat. However, in an oxygen-free environment, it can lead to the development of an unappealing purplish-red color and a decrease in the water-holding capacity of meat, thereby impacting the overall meat quality. Portulaca oleracea L. (POL) is a homology of medicine and food known for its exceptional antioxidant and antimicrobial properties., Results: The aim of our present study was to investigate the antioxidant and antimicrobial ability of n-butanol phase extract of POL and the effect of POL extract incorporation on the quality (water-holding capacity, shear force, color, and texture) and physicochemical (pH, total volatile base nitrogen, and total viable counts) attributes of vacuum-packed seasoned steaks at 4 °C over a 15-day period. Results showed that the POL extract had excellent antioxidant and antimicrobial capacity. Furthermore, the addition of POL extract significantly inhibited protein oxidation and microbial growth of steaks (P < 0.05), and improved the water-holding capacity, color properties, and tenderness (P < 0.05). Moreover, there were no significant differences (P > 0.05) in the color, water-holding capacity, or tenderness between the 0.5 and 1 g kg -1 POL extract treatment groups compared to the sodium nitrite control group., Conclusion: These results indicate that POL extract had the potential to replace sodium nitrite due to its ability to hinder protein oxidation and microbial growth of vacuum-packed seasoned steaks, while enhancing the color, water-holding capacity, and tenderness of seasoned steaks. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: The primary objective of this investigation was to assess the impact of pyrroline-5-carboxylate reductase 1 (PYCR1) on the progression of gastric cancer (GC), specifically focusing on tumor growth and metastatic potential., Methods: Surgical specimens from patients with different stages of GC were assayed for PYCR1 expression using immunohistochemistry. PYCR1 expression was manipulated by depletion or overexpression approaches in GC cells, and these cells were applied to explore the functional roles of PYCR1. Expression of apoptosis- and metastasis-related markers was quantified through quantitative real-time PCR and Western blot., Results: Higher PYCR1 expression was ascertained in surgical specimens from patients with GC as compared to noncancerous adjacent tissues. Additionally, PYCR1 overexpression in GC tissues was linked to adverse clinical outcomes. The depletion of PYCR1 in GC cells resulted in a pronounced reduction in proliferation, the induction of apoptosis, and the attenuation of invasion and metastasis. Conversely, its ectopic expression notably augmented proliferation, restricted apoptosis, and stimulated invasion and metastasis. In addition, the knockdown of PYCR1 resulted in a significant elevation in the activation of caspase 3, a key protein involved in apoptosis. This depletion also led to a decrease in the activation or expression of proteins associated with metastasis, such as phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), p-AKT serine/threonine kinase (AKT), and snail family transcriptional repressor 1 (Snail). Additionally, it resulted in an upregulation of E-cadherin expression. Conversely, the overexpression of PYCR1 notably increased the levels of p-PI3K, p-AKT, and Snail, while simultaneously reducing E-cadherin expression., Conclusion: PYCR1, by activating PI3K/AKT signaling, assumes a crucial role in governing malignant characteristics of GC cells, including proliferation, apoptosis, and metastasis. These findings underscore the promising potential of PYCR1 as a diagnostic biomarker and a target for tailored therapeutic interventions in patients with GC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Since the mid-2000s, drilling and production of oil and gas activities have grown exponentially in the southwestern United States. The clearing of pre-existing vegetation and topsoil to build well pads is known to have a broad range of ecological, biological, hydrological, and health impacts, therefore ecosystem restoration of the well pads is generally required. This process, however, is often complicated by limited funding, various governing bodies and ownership, and frequent extreme weather events. To ensure that well pad construction does not result in damaging, irreversible environmental change in the region, a prioritization strategy is needed to maximize the effectiveness of restoration efforts. The objective of this study is to develop a methodology to prioritize well pads where ecosystem restoration is urgently needed. In this methodology, a set of locational soil (e.g., soil fragility, wind and water erodibility) and land cover (e.g., land cover, proximity to streams) attributes were derived from publicly available datasets and a restoration priority score system along with a weighting factor were assigned to individual attributes. Accordingly, a total restoration priority score (TRPS) was calculated for individual well pads. This methodology was applied to a dataset of >10,000 well pads located in the Permian Basin and the surrounding area. This method effectively filtered out a large number of sites with low TRPS, and identified a small portion of high-score, clustered well pads. The identification of such well pads makes the logistical challenge of targeted restoration much easier for stakeholders tasked with maximizing the effectiveness of restoration efforts with limited funding. Despite some known limitations and inaccuracies, this method is low-cost and can be easily adaptable to humid and sub-humid systems, and even to restoration relevant to non-oil and gas exploration activities, such as solar and wind development, in the southwestern United States and many other areas worldwide., Competing Interests: Declaration of competing interest Junran Li reports article publishing charges and travel were provided by Project of Intergovernmental International Cooperation in Science and Technology Innovation (NO. 2019YFE0116500), Ministry of Science and Technology of China., (Copyright © 2023. Published by Elsevier B.V.)

Introductions: Identifying biological markers of colorectal cancer (CRC) development and prognosis and exploring the intrinsic connection between these molecular markers and CRC progression is underway. However, a single molecular tumor marker is often difficult to assess and predict the progression and prognosis of CRC. Consequently, a combination of tumor-related markers is much needed. Ki67, Her-2, and mutant P53 (MutP53) proteins play pivotal roles in CRC occurrence, progression and prognosis., Methods: Based on the expressions by immunochemistry, we developed a risk model, nomogram and lymph node metastasis model by R software and Pythons to explore the value of these proteins in predicting CRC progression, prognosis, and examined the relationship of these proteins with the CRC clinicopathological features from 755 (training set) and 211 CRC (validation set) patients collected from the hospital., Results: We found that Ki67 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular invasion, organization differentiation, and adenoma carcinogenesis. Moreover, Her-2 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, pMMR/dMMR, signet ring cell carcinoma, and organization differentiation. MutP53 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, adenoma carcinogenesis, signet ring cell carcinoma, organization differentiation, and pMMR/dMMR. Increased expression of each of the protein indicated a poor prognosis. The established risk model based on the three key proteins showed high predictive value for determining the pathological characteristics and prognosis of CRC and was an independent influencer for prognosis. The nomogram prediction model, which was based on the risk model, after sufficient evaluation, showed more premium clinical value for predicting prognosis. Independent cohort of 211 CRC patients screened from the hospital verified the strong predictive efficacy of these models. The utilization of the XGBoost algorithm in a lymph node metastasis model, which incorporates three crucial proteins, demonstrated a robust predictive capacity for lymph node metastasis., Discussion: The risk model, nomogram and lymph node metastasis model have all provided valuable insights into the involvement of these three key proteins in the progression and prognosis of CRC. Our study provides a theoretical basis for further screening of effective models that utilize biological markers of CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Huang, Wang and Xiao.)

A significant correlation is observed between Fusobacterium nucleatum ( F. nucleatum ) and the evolution of inflammatory bowel disease (IBD). Particularly, FomA, a critical pathogenic element of F. nucleatum , inflicts substantial detriment to human intestinal health. Our research focused on the development of recombinant Lactobacillus plantarum that expresses FomA protein, demonstrating its potential in protecting mice from severe IBD induced by F . nucleatum . To commence, two recombinant strains, namely L. plantarum NC8-pSIP409-pgsA'-FomA and NC8-pSIP409-FnBPA-pgsA'-FomA, were successfully developed. Validation of the results was achieved through flow cytometry, ELISA, and MTT assays. It was observed that recombinant L. plantarum instigated mouse-specific humoral immunity and elicited mucosal and T cell-mediated immune responses. Significantly, it amplified the immune reaction of B cells and CD4 + T cells, facilitated the secretion of cytokines such as IgA, IL4, and IL10, and induced lymphocyte proliferation in response to FomA protein stimulation. Finally, we discovered that administering recombinant L. plantarum could protect mice from severe IBD triggered by F. nucleatum , subsequently reducing pathological alterations and inflammatory responses. These empirical findings further the study of an innovative oral recombinant Lactobacillus vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Xiao, Zhang and Jiang.)

Background: This study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN)., Methods: We included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria., Results: Patients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05-4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02-15.88)., Conclusions: Urinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN., Impact: High levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN., (© 2023. The Author(s).)

This study aimed to assess the intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases. Hospitalized children with glomerular diseases participated in the study. For each patient, an overnight (9:00 p.m.-7:00 a.m.) urine was collected, followed by a 24-h urine (classified into four distinct periods: morning 7:00 a.m.-12:00 p.m., afternoon 12:00 p.m.-4:00 p.m., evening 4:00 p.m.-9:00 p.m., and overnight 9:00 p.m.-7:00 a.m.). The concentrations of protein, albumin, N-acetyl-beta-D-glucosaminidase, and epidermal growth factor (EGF) were measured and normalized by three correction factors (creatinine, osmolality, or specific gravity, respectively). Additionally, the 2nd overnight urine sample was grouped into different aliquots according to centrifugation, additives, storage temperature, or delayed processing. Twenty (14 boys, 6 girls) children were enrolled, with an average age of 11.3 years. Among the three correction factors, creatinine-normalized biomarkers provided the best agreements among different periods over 24 h. There were significant diurnal variations during 24 h in the concentrations of urinary protein, albumin, N-acetyl-beta-D-glucosaminidase, and EGF (p = 0.001, p = 0.003, p = 0.003, and p = 0.003, respectively). Evening urine overestimated 24-h urinary protein and albumin, while overnight urine underestimated 24-h urinary albumin. Urinary EGF showed low variability within a day or between the 2 days (coefficients of variation 10.2% and 10.6%, respectively) and excellent agreements (intraclass correlation coefficients > 0.9) with 24-h urinary concentration. Furthermore, urinary EGF was not affected by centrifugation, additives, storage temperature, or delayed processing of urine samples (all p > 0.05).  Conclusion: Given the diurnal variations of urinary biomarkers, urine samples should be collected during the same time period in clinical practice if possible. The results also extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice. What is Known: • Urinary biomarkers have been widely used or discussed in making diagnoses and therapy regimens and estimating the prognosis of pediatric glomerular diseases. It remains unclear whether their levels would be affected by the time of sample collection, processing methods, and storage conditions in hospitalized children with glomerular diseases. What is New: • The levels of both commonly used biomarkers and novel biomarkers exhibited diurnal variations in hospitalized children with glomerular diseases. • Our results extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice., (© 2023. The Author(s).)

Background: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear., Methods: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks., Results: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention., Conclusions: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety., Impact: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Neutrophil extracellular traps (NETs) is the key means for neutrophils to resist bacterial invasion. Sepsis is a systemic inflammatory response syndrome caused by infection., Methods: In our study, qRT-PCR was used to detect the gene expression in neutrophils, Western blot was used to detect the protein expression in mouse tissues and neutrophils, flow cytometry was used to detect the purity of neutrophils in the whole blood and immunofluorescence was used to detect the NETs formation., Results: In this study, we analyzed the NETs formation in the blood of patients with sepsis. The results showed that a large number of NETs appeared. And the expression of GPR109A in neutrophils of patients with sepsis was significantly up regulated. Then we collected neutrophils from WT mice and GPR109A -/- mice and found that GPR109A knockout could significantly inhibit the early NETs formation of neutrophils. The results also showed that knockout of GPR109A or inhibition of the NETs formation could increase the inflammatory response of liver, spleen, lung and kidney in mice, thus affecting the disease process of sepsis. Then we observed the death of mice in 16 days. The results showed that inhibiting the NETs formation could significantly affect the early mortality of mice, while knocking out GPR109A could directly affect the mortality of the whole period., Conclusions: This study confirmed the regulatory effect of GPR109A on early NETs formation for the first time, and provided a new target for the treatment of sepsis., (© 2023. The Author(s).)

Background: To detect the expression of HER-2 and P53 patients with gastric cancer and to analyze their correlation., Methods: A total of 249 gastric cancer patients with complete clinical data who received surgical treatment from China-Japan Union Hospital of Jilin University were selected. The expression of Her-2 and P53 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between HER-2 and P53 in gastric cancer were analyzed., Results: The positive rate of Her-2 and P53 expression was 37.3% (93/249) and 100% in all the specimens, respectively. The intensity of Her-2 expression was significantly different in patients with different degrees of gastric cancer cell differentiation (P = 0.012). Meanwhile, the expression of her-2 was closely related to whether the pathological type of gastric cancer was a signet-ring cell carcinoma (P = 0.022). Different percentage of positive P53 expression was closely related to the grade of tumor differentiation (P = 0.035) and positive Ki67 expression (P = 0.001). There was a significant positive correlation between HER-2 and P53 expression in gastric cancer (P = 0.003). These findings suggest that HER-2 and P53 have synergistic effects in gastric cancer., Conclusion: Her-2 and P53 are important markers for invasion and metastasis of gastric cancer. Combined detection of P53 and Her-2 expression in gastric cancer tissue can be used to assess prognosis and screen cancer patients at high risk of metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty., Results: This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658&#95;660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, L-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies., Conclusions: Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, L-carnitine, and betaine appears to be beneficial., (© 2022. The Author(s).)

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., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objective: To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis., Methods: Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family., Results: A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic., Conclusion: The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.

Background: The prognosis of acute kidney injury (AKI) varies in children with nephrotic syndrome (NS), data on factors predicting the recovery and recurrence of AKI in children with NS are limited. This study aimed to explore the possible factors predicting the recovery from and recurrence of AKI in children with primary NS., Methods: Children with primary NS complicated with AKI from 1993 to 2017 in a single centre were reviewed retrospectively. The clinical pictures and possible factors predicting the recovery from and recurrence of AKI in children with primary NS were investigated., Results: Sixty-eight episodes of AKI in 59 children with NS were analysed: 88.2% of AKI recovered within 3 months, and 2.9% of AKI did not recover after 3 months. Survival analysis revealed that leucocyturia is significantly related to the AKI recovery time (P = 0.001), and children with leucocyturia [22 (4, 79) days] recovered significantly slower than did children without leucocyturia [12.0 (2, 39) days]. Renal tubular and interstitial injury were prominent in children with leucocyturia, and 11.9% of children with index AKI experienced the recurrence of AKI., Conclusions: Most episodes of AKI that occurred in children with NS recovered completely. Leucocyturia is a significant factor predicting the recovery time of AKI., (© 2021. Japanese Society of Nephrology.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

A. fruticosa (Amorpha fruticosa L.) is widely used for revegetation in semiarid lands that undergo secondary salinization. Understanding A. fruticosa plants response to soil water and salt stress is essential for water irrigation management and proper revegetation practices. In this study, we measured sap flow, stomatal conductance, meteorological and soil characteristics in an A. fruticosa community that recently experienced secondary salinization in northwestern China. Results of our study showed that daytime and nocturnal sap flows averaged 804.37 g·cm -2 ·day -1 and 46.06 g·cm -2 ·day -1 , respectively, during the growing season. Within individual days, the highest sap flow appeared around noon local time and followed a similar pattern of photosynthetically active radiation (PAR). Despite the significant effect of meteorological factors on the characteristics of sap flow, our study highlighted that the sap flow of A. fruticosa is strongly regulated by the availability of soil relative extractable water (REW). The daytime sap flow, which is predominant compared to nocturnal sap flow, was strongly affected by PAR, air temperature and vapor-pressure deficit. With water stress in the top 40 cm of the soil (REW 0-40 cm  < 0.4), daytime sap flow displayed a strong relationship with soil water content (SWC) (positive) and soil electrical conductivity (EC) (negative) in the relatively shallow soil profile (up to 40 cm). For the nocturnal sap flow, our results suggest that in the absence of soil water stress (REW 0-40 cm  > 0.4), the nocturnal sap flow is mainly used to replenish the stem water content and sustain nocturnal transpiration. Under soil water stress, nocturnal sap flow is mainly used to replenish stem water content. The results of our study indicate that it is necessary to shorten the irrigation cycle during the primary growing period (May-July) of A. fruticosa. Moreover, in the absence of soil water stress (REW 0-40 cm  > 0.4), A. fruticosa can survive well in an saline environment with soil EC < 5 mS·cm -1 .

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 < 0.001), after adjustment for age. In 38 patients with longitudinal follow-up, we observed a significant correlation between uEGF/Cr and eGFR slope (r = 0.58, p < 0.001). Patients with lower uEGF/Cr level were at increased risk of progression to a higher CKD stage. uEGF/Cr was able to distinguish progressors from non-progressors with an AUC of 0.88, versus 0.77 by eGFR and 0.81 by 24-h urinary protein (24-h UP)., Conclusions: Our study suggests that uEGF/Cr is a promising biomarker for accelerated kidney function decline in pediatric patients with Alport syndrome. It may help to identify patients at high risk of progression for targeted clinical care and improve the patients' stratification in interventional trials.

Objective: To analyze the clinical and genetic features of X-linked Alport syndrome (XLAS) in men positive for the collagen α5(Ⅳ) chain in epidermal basement membrane., Method: This was a retrospective study. Totally 725 families were diagnosed as Alport syndrome in Department of Pediatrics of Peking University First Hospital during January 1998 to December 2014, among them 450 patients were males with XLAS. Patients who met both of the following two criteria were included in this study. (1)Patients underwent α5(Ⅳ) chain staining in the epidermal basement membrane. (2)Mutations in COL4A5 gene were detected.Mann-Whitney test and χ(2) test were used., Result: Totally 140 males with XLAS were included in this study, 18 cases were α5 (Ⅳ)-positive and 122 cases were α5 (Ⅳ)-negative. The two groups of patients were compared, the median age at analysis was 11.0 vs. 7.2 years (Z = -1.839, P = 0.066), the 24-hour urine protein was 1.50 vs. 0.57 g/d (Z = -1.212, P = 0.226), the rate of hearing loss was 28% vs. 53% (χ(2) = 3.619, P = 0.067), the number of patients progressed to end stage renal disease (ESRD) was 4 vs. 12 (χ(2) =2.377, P = 0.128), the median age of ESRD was 31.0 vs. 16.6 years (Z = -2.554, P = 0.011), the rate of missense mutations in COL4A5 gene was 67% vs. 52% (χ(2) = 1.424, P = 0.313)., Conclusion: Compared the two groups of patients with positive and negative staining for the collagen Ⅳ α5 chain in epidermal basement membrane, there was no significant difference in the proteinuria level, the rate of hearing loss and genotype of COL4A5 gene. But the patients with positive staining progressed to ESRD significantly later than the patients with negative staining.

Objective: IgA nephropathy is the most common type of glomerulonephritis in the world. Its clinical and pathological manifestations vary. A few of the patients with IgA nephropathy present with rapidly progressive glomerulonephritis (RPGN) and/or crescent formation. Their conditions are serious and acute, but there are few reports on their characteristics, treatment and outcome. This study aimed to analyze the clinicalopathological features, treatment and prognosis of primary IgA nephropathy in children, to provide a reference for clinical diagnosis and treatment., Method: A retrospective study was conducted in children with primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis admitted to our department from 2000 to 2014. The patients meeting the inclusion and exclusion criteria were included. Patients were divided into RPGN group and non-RPGN group according to the clinical manifestations, crescent formation group and non-crescent group, crescentic IgA nephropathy group and non-crescentic IgA nephropathy group according to renal biopsy. Their clinical manifestations and pathological features, treatment and prognosis were compared., Result: A total of 265 patients were recruited, 10 patients (3.8%) had RPGN, 151 patients (57.0%) had crescent formation, 19 cases (7.2%) showed crescentic IgA nephropathy.Compared with non-RPGN group, RPGN group showed more gross hematuria, higher serum creatinine, lower creatinine clearance correction at biopsy and follow-up, and more crescentic IgA nephropathy (P<0.05). The percent of patients who received methylprednisolone pulse and blood purification therapy in RPGN group is higher than that of non-RPGN group (P<0.05). Compared with non-crescent group, crescent formation group showed more gross hematuria at biopsy and follow-up, higher serum creatinine at biopsy, lower creatinine clearance correction, more 24-hour urinary protein at biopsy and higher serum creatinine at follow-up (P<0.05). The percentage of patients received more methylprednisolone pulse, oral steroids, cyclophosphamide pulse in crescent formation group was higher than that of non-crescent group (P<0.05). Compared with non-crescentic IgA nephropathy group, crescentic IgA nephropathy group showed more RPGN percent, higher serum creatinine, more 24-hour urinary protein at biopsy (P<0.05). The percentage of patients who received more methylprednisolone pulse and blood purification therapy in crescentic IgA nephropathy group was more than non-crescentic IgA nephropathy group (P<0.05). At follow-up, 20.0% of the patients with RPGN and crescent nephritis returned to normal renal function and the percent of crescent glomerulonephritis but not RPGN was 71.4%, RPGN but not crescent glomerulonephritis was 80.0%, crescent formation but not crescent nephritis was 87.5%., Conclusion: In primary IgA nephropathy with crescent formation and/or rapidly progressive glomerulonephritis, the patients with both RPGN and crescentic IgA nephropathy showed the worst clinical manifestations, its prognosis was worst while the patients with crescent formation showed the mildest clinical manifestations and best prognosis.

Objective: In this study, we investigated the role of miR-300 in regulating cell proliferation and invasion of gastric cancer cells., Methods: MicroRNA and protein expression patterns were compared between gastric cancer tissue and normal tissue and between two different prognostic groups. The up-regulation of miR-300 was confirmed by real-time reverse transcription polymerase chain reaction and its expression was analyzed in AGS gastric cancer cells., Results: We observed that miR-300 expression was frequently and dramatically up-regulated in human gastric cancer tissues and cell lines compared with the matched adjacent normal tissues and cells. We further showed that transient and stable over-expression of miR-300 could promote cell proliferation and cell cycle progression. Moreover, p53, a key inhibitor of cell cycle, was verified as a direct target of miR-300, suggesting that miR-300 might promote gastric cancer cell proliferation and invasion by increasing p53 expression., Conclusion: Our findings indicated that miR-300 up-regulation might exert some sort of antagonistic function by targeting p53 in gastric cancer cell proliferation during gastric tumorigenesis.

Objective: To analyze the relationship between hyperuricemia and primary nephrotic syndrome in childhood., Method: A retrospective study was carried out in 107 children with primary nephrotic syndrome. The clinical data were analyzed with statistical methods to identify the related factors with hyperuricemia., Result: The morbidity of hyperuricemia in children with primary nephrotic syndrome was 45% (48/107). Compared to those in normal serum uric acid group, the incidence of hypertension (33%, 16/48), serum triglyceride [2.59(1.62-3.87) mmol/L], creatinine [43.85(33.38-56.38)mmol/L], urea [6.11(3.77-8.40)mmol/L] and blood uric acid/creatinine ratio [9.30(7.03-12.72)] increased while creatinine clearance rate [141.74(103.57-160.97)ml/(min·1.73 (2))] decreased in hyperuricemia group., Conclusion: Hyperuricemia in children with primary nephrotic syndrome correlated with the increase of serum creatinine, urea and blood uric acid/creatinine ratio, the decrease of creatinine clearance rate and the occurance of hypertension.

Objective: To investigate the clinical characteristics, renal pathology, treatment and prognosis of children with atypical hemolytic uremic syndrome associated with H factor antibody., Method: Four children less than 18 yr of age admitted from Nov. 2010 to May 2011 in Peking University First Hospital were included. They all met the criteria for atypical hemolytic uremic syndrome and with positive serum anti factor H antibody. They aged from 5 to 11 yr. Data on clinical manifestations, renal pathology, treatment and prognosis were analyzed., Result: All of the 4 cases had gastrointestinal symptoms such as vomiting, abdominal pain, or abdominal distension. None of them had diarrhea. Two children had hypertension. One child had episodes of convulsion. One child had history of atypical hemolytic uremic syndrome. All of them had low serum complement C3. Three of them had low serum factor H (38.0, 88.4, 209.4 mg/L). All of them had serum antibody to factor H (1: 7 068, 1: 1 110, 1: 174, and 1: 869). Three of them received renal biopsy, all of them showed thrombotic microangiopathy. All of them were treated with steroid combined with mycophenolate mofetil. Two children received plasma exchange. They were followed up for 8 to 29 months. The renal function became normal and proteinuria relieved in all of them. The serum factor H concentration increased to 405.8, 155.8 and 438.4 mg/L, respectively. The titer of anti factor H antibody decreased to 1: 119, 1: 170, 1: 123, and 1: 674, respectively., Conclusion: Gastrointestinal symptom is common in children with atypical hemolytic uremic syndrome associated with H factor antibody. Hypocomplementemia was observed in all of them. Steroid combined with mycophenolate mofetil seemed to be effective for them. The monitoring of serum factor H and antibody to factor H may help diagnosis and treatment.

Unrestrained glycolysis characterizes energy meta-bolism in cancer cells. Thus, antiglycolytic reagents such as 2-deoxy-D-glucose (2-DG) and 3-bromopyruvate (3-BrPA) may be used as anticancer drugs. In the present study, we examined the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells and investigated whether these effects were regulated by hypoxia-inducible factor-1α (HIF-1α). To this end, 2-DG and 3-BrPA were administered to wild-type (wt) MiaPaCa2 and Panc-1 pancreatic cancer cells that were incubated under hypoxic (HIF-1α-positive) or normoxic (HIF-1α-negative) conditions. In addition, 2-DG and 3-BrPA were also administered to si-MiaPaCa2 and si-Panc-1 cells that lacked HIF-1α as a result of RNA interference. Following drug exposure, cell population was measured using a viability assay. Both HIF-1α-positive and HIF-1α-negative MiaPaCa2 cells were further studied for their expression of Cu/Zn-superoxide dismutase (SOD1) and poly(ADP-ribose) polymerase (PARP) and for their contents of ATP and fumarate. In the viability assay, either 2-DG or 3-BrPA decreased the tested cells. Concurrent use of 2-DG and 3-BrPA resulted in a greater decrease of cells and also facilitated ATP depletion. In addition, 3-BrPA was seen to both decrease SOD1 and increase fumarate, which suggests that the reagent impaired the mitochondria. 3-BrPA also decreased both full-length PARP and cleaved PARP, which suggests that 3-BrPA-induced decrease in cell population was a result of cell necrosis rather than apoptosis. When HIF-1α was induced in wt-MiaPaCa2 cells by hypoxia, some effects of 2-DG and 3-BrPA were attenuated. We conclude that: i) concurrent use of 2-DG and 3-BrPA has better anticancer effects in pancreatic cancer cells, ii) 3-BrPA impairs the mitochondria of pancreatic cancer cells and induces cell necrosis, and iii) HIF-1α regulates the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells.