[Mid-term efficacy evaluation of ABO incompatible living relative kidney transplantation based on protocol biopsy].

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed. Combined with blood type antibody levels and renal function recovery, the mid-term efficacy of ABOi-KT was evaluated. Results: Among the 23 recipients, there were 19 males and 4 females; age range from 19 to 47 years old [(29.6±6.7) years old], all underwent ABOi-KT successfully after receiving desensitization treatment. The follow-up time was (44.6±22.4) months, of which 22 cases were followed up for more than 1 year. The incidence rates of rejection reactions at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were 15.0% (3/20), 11.1% (1/9), 7.7% (1/13), 25.0% (3/12), and 12.5% (1/8), respectively. For receptors with rejection reactions, targeted anti-rejection therapy was performed based on clinical symptoms and various indicators. Borderline T cell mediated rejection (TCMR) can be converted to mild tubular inflammation after anti-rejection treatment. The positive rate of complement C4d in peritubular capillaries was 95.0% (19/20) one week after surgery, and the positive rate of complement C4d was 100% at 3 and 12 months after surgery. The cumulative survival rates at 1, 3, 5, and 7 years after surgery were all 100%. The cumulative survival rates at 1, 3, 5, and 7 years after kidney transplantation were 100%, 93.3%, 84.0%, and 84.0%, respectively. Except for 2 recipients who underwent transplantation in 2017 and experienced kidney failure at 30 and 49 months after surgery, all other transplanted kidneys survived. Conclusions: The results of routine renal transplant biopsy show that ABOi-KT has a good mid-term therapeutic effect. The pathological changes of ABOi-KT can be dynamically observed through routine renal transplant biopsy and targeted treatment for rejection reactions can be provided accordingly.

[Long-term outcomes of childhood steroid-sensitive nephrotic syndrome].

Objective: To investigate the long-term outcomes and risk factors in children with steroid-sensitive nephrotic syndrome (SSNS). Methods: A retrospective cohort study was conducted on newly onset SSNS admitted to the Department of Pediatrics of the First Affiliated Hospital of Sun Yat-sen University from January 2006 to December 2010 and 105 cases with follow-up for more than 10 years were included. Clinical data including general characteristics, clinical manifestation, laboratory tests, treatment and prognosis. The primary outcome was the clinical cure, and the secondary outcomes were relapse or ongoing immunosuppressive treatment within the last 1 year of follow-up and complications at the last follow-up. According to the primary outcome, the patients were divided into clinical cured group and uncured group. Categorical variables were compared between 2 groups using the χ2 or Fisher exact test, and continuous variables by t or Mann-Whitney U test. Multiple Logistic regression models were used for multivariate analysis. Results: Of the 105 children with SSNS, the age of onset was 3.0 (2.1, 5.0) years, and 82 (78.1%) were boys, 23(21.9%) were girls. The follow-up time was (13.1±1.4) years; 38 patients (36.2%) had frequently relapsing or steroid-dependent nephrotic syndrome (FRNS or SDNS) and no death or progression to end-stage kidney disease. Eighty-eight patients (83.8%) were clinically cured. Seventeen patients (16.2%) did not reach the clinical cure criteria, and 14 patients (13.3%) had relapsed or ongoing immunosuppressive treatment within the last year of follow-up. The proportion of FRNS or SDNS (12/17 vs. 29.5% (26/88), χ2=10.39), the proportion of treatment with second-line immunosuppressive therapy (13/17 vs. 18.2% (16/88), χ2=21.39), and the level of apolipoprotein A1 at onset ((2.0±0.5) vs. (1.7±0.6) g/L, t=2.02) in the uncured group were higher than those in the clinical cured group (all P<0.05). Multivariate Logistic regression analysis showed that patients treated with immunosuppressive therapy had an increased risk of not reaching clinical cure in the long term (OR=14.63, 95%CI 4.21-50.78, P<0.001). Of the 55 clinically cured patients who had relapsed, 48 patients (87.3%) did not relapse after 12 years of age. The age at last follow-up was 16.4 (14.6, 18.9) years, and 34 patients (32.4%) were ≥18 years of age. Among the 34 patients who had reached adulthood, 5 patients (14.7%) still relapsed or ongoing immunosuppressive treatment within the last year of follow-up. At the last follow-up, among the 105 patients, 13 still had long-term complications, and 8 patients were FRNS or SDNS. The proportion of FRNS or SDNS patients with short stature, obesity, cataracts, and osteoporotic bone fracture was 10.5% (4/38), 7.9% (3/38), 5.3% (2/38), and 2.6% (1/38), respectively. Conclusions: The majority of SSNS children were clinically cured, indicating a favorable long-term prognosis. History of treatment with second-line immunosuppressive therapy was the independent risk factor for patients not reaching the clinical cure criteria in the long term. While it is not uncommon for children with SSNS to persist into adulthood. The prevention and control of long-term complications of FRNS or SDNS patients should be strengthened.

[Role of preoperative ultrasound-guided inferior parathyroid gland localization and new classification to assist intraoperative search and protection of parathyroid glands].

Objective: To investigate the role and significance of ultrasound-guided inferior parathyroid gland (IPTG) localization in searching and protecting parathyroid glands before thyroid surgery. Methods: A randomized controlled trial study was conducted. A total of 306 patients (433 cases of lateral parathyroidectomy) who underwent primary thyroidectomy and central lymph node dissection in Beijing Tongren Hosipital from March to October 2021 were enrolled. In order to locate IPTG more quickly and effectively, new IPTG classification and the definition of quadrant position were carried out. The patients were divided into the study group (n=228) and the control group (n=205). The study group underwent ultrasound-guided IPTG examination before operation and measured the distance between the IPTG and the lower pole of the thyroid and the midline of the trachea. During the operation, the IPTG was found and protected depending on the localization. The control group did not use any auxiliary preoperative positioning method. The distribution ratio of IPTG and the coincidence rate between intraoperative validation and ultrasound localization were calculated. Results: There were 306 patients enrolled in the final analysis (95 males and 211 females), with a median age of 41 years old (18-70). Type Ⅱ and Ⅲ IPTG accounted for 77.2% (176/228) of the total cases. The total coincidence rate ranged from 72.8% to 79.4% in different IPTG groups. Type Ⅲ and quadrant 2 IPTG had the highest coincidence rate [92.4% (73/79) and 92.9% (79/85), respectively]. The study group had better in situ retention rate [82.0% (187/228) vs 73.2% (150/205), χ2=4.896, P=0.027] and less implantation rate [8.8% (20/228) vs 16.1% (33/205), χ2=5.393, P=0.020] than those of the control group. The in situ retention rate were better in type Ⅲ IPTG group, compared with those of the control group [94.9% (74/78) vs 77.4% (48/62), χ2=7.898, P=0.005]. There was no permanent hypoparathyroidism in two groups and the temporary hypoparathyroidism rate was 32.0% (24/75) and 34.6% (18/52), respectively (χ2=0.095, P=0.758). Conclusion: Ultrasound-guided IPTG localization examination has important implications for searching and protecting IPTG during operation, which can significantly increase in situ retention rate of IPTG and decrease the implantation rate.

[Study on efficacy, recurrence rate and related risk factors between ablation index and contact force guided radiofrequency ablation of paroxysmal atrial fibrillation in elderly patients].

Objective: To compare the efficacy, safety and recurrence rate between ablation index (AI) and contact force (CF) guided radiofrequency ablation of paroxysmal atrial fibrillation in elderly patients. Methods: Elderly patients (age ≥60 years) with paroxysmal atrial fibrillation who received radiofrequency ablation for the first time at Department of Cardiology, Beijing Friendship Hospital from April 2018 to April 2019 were enrolled. Patients were divided into 2 groups: AI-group (n=40) and CF group (n=37) depending on their ablation methods. Follow-up was performed until 1 year post the procedure, and efficacy related indexes like first-pass pulmonary vein isolation (PVI) rate, ablation duration, operation duration and major complications were compared between 2 groups. The recurrence rates between 2 groups and related risk factors after radiofrequency ablation were analyzed. Results: A total of 77 patients [mean age (68.5±6.4) years, 40 were male] were enrolled at last. In AI guided patients, frequency of first-pass PVI rate was higher [52.5%(21 cases) vs 29.7%(3 cases), P=0.011] with a shorter ablation duration [(24.5±1.7) min vs (33.7±2.2) min, P<0.001] and operation duration [(136.6±6.1) min vs (139.7±7.4) min, P=0.048] compared with CF guided group. At 1 year follow-up, AI group showed an amendatory recurrence rate in Kaplan-Meier analysis (22.5% vs 40.5%,log-rank P=0.048). Multivariate Cox regression analysis showed that CF guided ablation (HR=3.272,95%CI:1.319-8.114,P=0.011), enlarged anteroposterior diameter of the left atrium (HR=4.233,95%CI:1.511-11.862,P=0.006) and complicated with coronary heart disease (HR=4.829,95%CI:1.399-16.666,P=0.013) were independent risk factors for recurrence of atrial fibrillation in elderly patients. Conclusions: Compared with CF guided ablation, radiofrequency ablation of paroxysmal atrial fibrillation in elderly patients guided by AI showed a higher first-pass PVI rate, shorter procedure duration of both ablation time and total operation time, meanwhile a lower recurrence rate. Further analysis revealed that different ablation alternation (AI or CF), enlarged anteroposterior diameter of left atrium, and complicated with coronary heart disease are independent risk factors for recurrence after radiofrequency ablation of atrial fibrillation in elderly patients.

[Treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis].

Objectives: To analyze the clinical characteristics, treatment effectiveness and long-term prognosis of childhood-onset lupus nephritis (LN), and to explore the risk factors for progression to end-stage renal disease (ESRD). Methods: In this retrospective study, the clinical data including general conditions, clinical manifestations, laboratory examinations, treatment, following up (till December 31st, 2020) and prognosis of 343 children with LN who were treated and followed up in the First Affiliated Hospital of Sun Yat-sen University from January 1, 2003 to December 31, 2019 were analyzed. Complete remission rates were compared between different pathological types according to renal biopsies and flare rates were compared between complete remission group and partial remission group according to the treatment effectiveness after 6 months of induction treatment. To investigate the risk factors of ESRD, the prognosis of flare and non-flare cases, and of cases with normal and elevated serum creatinine levels at baseline, was compared. Chi-squared tests were used for comparison between groups, and cumulative survival rate and renal survival rates were calculated by Kaplan-Meier survival analysis. Risk factors for ESRD were analyzed by COX regression model. Results: Among the 343 children, 68 were males (19.8%) and 275 were females (80.2%) with a median age of 13.0 (11.0, 16.0) years. Regarding the renal symptoms, 305 (88.9%) children had proteinuria and 245 (71.4%) had hematuria; while for extra-renal manifestations, 273 (79.6%) had anemia, 183 (53.4%) had rashes and 165 (48.1%) had fever. A total of 212 (61.8%) children had severely active SLE at initial presentation. After 6 months of induction treatment, the complete remission rate was 63.8% (219/343) and the partial remission rate was 27.1% (93/343). The complete remission rate was significantly higher in type Ⅰ and type Ⅱ LN compared to type Ⅳ LN (10/12 vs. 82/135 (60.7%), χ²=3.936, P=0.047). One hundred and ten children who achieved remission, including complete remission and partial remission, experienced renal flare with a flare rate of 35.3% and a mean time to flare was (43.2±28.4) months. There was no significant difference in flare rates between complete and partial remission group (36.1% (79/219) vs. 33.3% (31/93), χ²=3.394, P=0.065). The follow-up time of all the children was 60.4 (32.3, 100.9) months. During the follow-up period, 15 children died and the cumulative survival rates at 3, 5 and 10 years were 97.2%, 96.4% and 93.3%, respectively; 14 children progressed to ESRD and the cumulative renal survival rates at 3, 5, and 10 years were 99.2%, 97.1%, and 93.4%, respectively. COX multivariate analysis demonstrated that elevated serum creatinine at baseline, nephritic flare and nephrotic flare were independent risk factors for progression of ESRD (hazard ratio (HR)=3.575, 21.550 and 8.590, 95%CI 1.127-11.341, 2.394-194.027 and 1.042-70.823, P=0.031, 0.006, and 0.046, respectively). Conclusions: Children with LN are characterized by high SLE disease activity and multi-system involvement at onset. After 6 months of induction treatment, most of LN children could achieve clinical remission but some would experience renal flare. Nephritic flare, nephrotic flare and elevated serum creatinine at onset are independent risk factors for the progression of ESRD in children with LN.

[Diagnostic and predictive values of three criterias of acute kidney injury in children with chronic kidney disease].

Objective: To compare the consistency in diagnosing and staging acute kidney injury (AKI) in children with chronic kidney disease (CKD) according to three criterias. Methods: Children with CKD hospitalized in the First Affiliated Hospital of Sun Yat sen University from January 2013 to December 2019 were analyzed retrospectively. These patients underwent serum creatinine examination more than twice during hospitalization. The AKI diagnosis and staging were performed for each patient according to the 2007 pRIFLE, 2012 KDIGO and 2018 pROCK criteria respectively. All the children were followed up for 1 year after discharge through outpatient visit, re-hospitalization or online consultation. The clinical characteristics and prognosis of CKD children with or without AKI that were diagnosed by 3 criteria were compared. Analysis of variance and chi-squared tests were used for the comparison among groups. Concordance between the different diagnostic criteria was evaluated using Cohen's kappa coefficient. Result: A total of 2 551 children with CKD were included in this study, with an age of (8±4) years. There were 1 628 boys and 923 girls. Nephrotic syndrome was the most prevalent primary disease (55.4%), followed by lupus nephritis (11.2%) and purpura nephritis (8.2%). Among all stages of CKD, CKD category G1 was the most common type (2 146 cases, 84.1%), followed by CKD category G2 (221 cases, 8.7%). AKI occurence rates according to pRIFLE, KDIGO and pROCK criteria were 33.9% (866/2 551), 26.2%(669/2 551) and 19.5% (498/2 551) respectively (χ²=136.3,P<0.01). The diagnostic consistency within three criteria for AKI was high in children with CKD (κ=0.702), but AKI staging consistency was low (κ=0.329). Both the diagnosis and staging consistency of three AKI criteria were poor in children with CKD category G5 (all κ<0.400). The length of hospital stay (LOS), hospitalization costs, the occurence of intensive care unit (ICU) admission and in-hospital mortality were significantly higher in children with AKI diagnosed by different criteria (P<0.05). After 1-year follow-up, the repeated admission rate and CKD staging progress significantly increased in children with AKI (P<0.05). In children with baseline serum creatinine≥200 µmol/L, compared with children who did not experience AKI during hospitalization, the LOS and the hospitalization costs in children who were diagnosed AKI according to pRIFLE or pROCK criteria was significantly higher (P<0.05). However, there was no significant difference in the LOS and hospitalization costs between children with or without AKI who were diagnosed according to KDIGO criteria (all P>0.05). Conclusions: AKI diagnosed by all of the three criteria (pRIFLE, KDIGO and pROCK criteria) was associated with the poor prognosis in children with CKD. However, in those whose baseline serum creatinine≥ 200 µmol/L, AKI diagnosed by pRIFLE and pROCK criteria could better reflect the poor outcomes than by KDIGO criteria.

Bioinformatic analysis for the identification of potential gene interactions and therapeutic targets in atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is the most common type of tachycardia. The major injury caused by AF is a systemic embolism. Although AF therapies have evolved substantially, the success rate of sinus rhythm maintenance is relatively low. The reason is the incomplete understanding of the AF mechanisms. MATERIALS AND METHODS: A Gene Expression Omnibus (GEO) dataset (GSE79768) was downloaded. Differentially expressed genes (DEGs) were identified by bioinformatic analysis. Enriched terms and pathways were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was constructed to determine regulatory genes. CytoHubba and the Molecular Complex Detection (MCODE) algorithm were used to identify potential hub genes and important modules. The Predicting Associated Transcription Factors From Annotated Affinities (PASTAA) method was used to predict transcription factors (TFs). RESULTS: Two hundred thirty-five upregulated DEGs and seventy-seven downregulated DEGs were identified. In the GO biological process, cellular component, and molecular function analyses, positive regulation of cell migration, anchoring junctions, and cell adhesion molecule binding were enriched significantly. The Hippo signalling pathway was the most significantly enriched pathway. In the PPI network analysis, we found that Class A/1 (rhodopsin-like receptors) may be the critical module. Ten hub genes were extracted, including 6 upregulated genes and 4 downregulated genes. CXCR2, TLR4, and CXCR4 may play critical roles in AF. In the TF prediction, we found that Irf-1 may be implicated in AF. CONCLUSIONS: We found that the CXCR4, TLR4, CXCR2 genes, the Hippo signalling pathway and the class A/1 (rhodopsin-like receptors) module may play critical roles in AF occurrence and maintenance, which may provide novel targets for AF treatment.

Can elevated concentrations of ALT and AST predict the risk of 'recurrence' of COVID-19?

'Recurrence' of coronavirus disease 2019 (COVID-19) has triggered numerous discussions of scholars at home and abroad. A total of 44 recurrent cases of COVID-19 and 32 control cases admitted from 11 February to 29 March 2020 to Guanggu Campus of Tongji Hospital affiliated to Tongji Medical College Huazhong University of Science and Technology were enrolled in this study. All the 44 recurrent cases were classified as mild to moderate when the patients were admitted for the second time. The gender and mean age in both cases (recurrent and control) were similar. At least one concomitant disease was observed in 52.27% recurrent cases and 34.38% control cases. The most prevalent comorbidity among them was hypertension. Fever and cough being the most prevalent clinical symptoms in both cases. On comparing both the cases, recurrent cases had markedly elevated concentrations of alanine aminotransferase (ALT) (P = 0.020) and aspartate aminotransferase (AST) (P = 0.007). Moreover, subgroup analysis showed mild to moderate abnormal concentrations of ALT and AST in recurrent cases. The elevated concentrations of ALT and AST may be recognised as predictive markers for the risk of 'recurrence' of COVID-19, which may provide insights into the prevention and control of COVID-19 in the future.

The effect of Casitas b-lineage lymphoma b on regulating T follicular helper in lupus nephritis.

OBJECTIVE: The purpose of this study was to investigate the effect of Casitas b-lineage lymphoma b (Cblb) on the regulation of T follicular helper (Tfh) in the development of lupus nephritis. MATERIALS AND METHODS: The Tfh (CD4+CXCR5+PD-1+) cells in peripheral blood were analyzed by flow cytometry. Forty mice were divided into 4 groups (10/group), WT, lpr, Cblb-/- and lpr.Cblb-/-. Urine protein, serum creatinine, blood urea nitrogen (BUN), dsDNA, and antinuclear antibody (ANA) titer of mice were monitored once every four weeks. Peripheral blood mononuclear cells (PBMCs) from mice were collected to assess circulating Tfh. The expressions of Cblb in Tfh cells were regulated by transfecting siRNA and overexpression plasmid approach in vitro. RESULTS: The patients with lupus nephritis (LN) had abnormal renal clinical manifestations compared with healthy volunteers. The peripheral Tfh cells were increased and the expression of Cblb were downregulated in patients with LN (p<0.05). Both lpr mice and lpr.Cblb-/- mice had LN symptoms. LN symptoms were more serious in lpr.Cblb-/- mice compared with that in lpr mice (p<0.05). The number of Tfh cells in peripheral blood from lpr.Cblb-/- mice was significantly higher than that from lpr mice (p<0.05). Overexpression of Cblb in Tfh cells led to reduction of IgG expression, while the knockdown of Cblb in Tfh cells was accompanied by increased expression of immunoglobulin (IgG) (p<0.05). CONCLUSIONS: Cblb showed a negative regulatory effect on Tfh. The deletion of Cblb may be a key factor in progression of renal injury.

[Differences in efficacy between drug-eluting beads transbronchial arterial chemoembolization combined with systemic chemotherapy and systemic chemotherapy alone for unresectable lung squamous cell carcinoma].

Objective: To investigate the differences in efficacy between drug-eluting beads transbronchial arterial chemoembolization (DEB-BACE) combined with systemic chemotherapy and systemic chemotherapy alone for unresectable lung squamous cell carcinoma. Methods: Totally 60 cases of unresectable lung squamous cell carcinoma undergoing systemic chemotherapy in Yancheng Third People Hospital were retrospectively selected as the research object. According to patients' wishes, they were divided into chemotherapy-only group (group A) and combined treatment group (group B). Group A received gemcitabine combined with cisplatin chemotherapy. DEB-BACE was applied in the first half, and systemic chemotherapy was administered in the second half (starting 3 d after BACE). The first half and the second half of the chemotherapy dose were 1/2 of the drug dose in the chemotherapy alone group. The short-term efficacy, incidence of toxic side effects, peripheral blood T lymphocyte subsets, serum vascular endothelial growth factor (VEGF) levels, and survival time were compared between the two groups. Results: After 2 cycles of treatment, the total effective rates of group A and group B were 50.0% (15/30) and 76.7% (23/30) (P<0.05), the incidence of nausea and vomiting (63.3% vs 20.0%), decreased appetite (76.7% vs 43.3%), hair loss (86.7% vs 40.0%), and bone marrow suppression (40.0% vs 10.0%) in group A were higher than in group B (all P<0.05). After 2 cycles of treatment, the levels of CD3(+), CD4(+)and CD4(+)/CD8(+)in the two groups were higher than before treatment (group A: 47.7%±6.6% vs 52.3%±7.7%, 31.5%±4.9% vs 34.7%±5.8%, 1.05±0.24 vs 1.18±0.32; group B: 49.2%±7.0% vs 62.0%±14.0%,29.2%±5.5% vs 42.2%±7.3%, 1.07±0.26 vs 1.39±0.42; all P<0.05), while the level of CD8(+)was lower than before treatment (group A: 30.4%±5.4% vs 24.5%±4.8%; group B: 29.5%±4.1% vs 21.1%±4.5%; all P<0.05). The CD3(+), CD4(+), and CD4(+)/CD8(+) levels in group A were lower than those in group B (P<0.05), while CD8(+)level was higher than in group B (P<0.05). After 2 cycles of treatment, the VEGF levels in the two groups were lower than before treatment (group A: (423±85) vs (352±64) ng/L; group B: (404±114) vs (296±66) ng/L; P<0.05), and the VEGF level in group A was higher than that in group B (P<0.05). The 1-year survival rates of groups A and B were 54.9% and 77.9%, and the 2-year survival rates were 17.2% and 41.7% (Log rank χ(2)=4.750, P=0.029). Conclusion: DEB-BACE combined with systemic chemotherapy is superior to systemic chemotherapy in the treatment of unresectable lung squamous cell carcinoma. It can reduce toxic and side effects, improve immune function and prolong survival time, which is worthy of clinical application.

MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM resistance.

The article "MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM resistance, by Chen LZ, Ding Z, Zhang Y, He ST, Wang XH, published in Eur Rev Med Pharmacol Sci. 2018 Jun;22(12):3734-3741. DOI: 10.26355/eurrev_201806_15253. PMID: 29949147" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.

[Genetic variants of familial hematuria associated genes in three families with hematuria with probands initially diagnosed as IgA nephropathy].

Objective: To examine genetic variants of familial hematuria (FH) associated genes in 3 families with hematuria with probands initially diagnosed with IgA nephropathy (IgAN). Methods: A retrospective analysis was performed on the clinical data, laboratory tests and genetic test results of three children with hematuria and the probands in three families with hematuria. The families were ascertained at the Department of Pediatrics, Fuzhou General Hospital of Nanjing Military Command from August 2014 to May 2018. Results: The proband of Family One, an 8-year-old boy, manifested gross hematuria. His renal biopsy pathology revealed IgAN. His father also manifested hematuria. Genetic testing showed that the proband and his father carried a heterozygous variant of the CFHR5 gene,533A>G (Asn178Ser). The child of Family Two, a 4-year-old girl, manifested hematuria. Her father, the proband of the family, was 36 years old, and manifested hematuria, proteinuria, high-frequency sensorineural deafness and renal insufficiency. He was diagnosed as IgAN according to clinical manifestations, renal pathology and routine immunohistochemistry without renal biopsy electron microscopy, renal tissue type Ⅳ collagen α3, α4, α5 chains immunofluorescence and skin type Ⅳ collagen α5 chain immunofluorescence. Genetic testing showed that the girl carried a heterozygous variant of the COL4A5 gene,566G>T (Gly189Val), and her father carried the hemizygous variant. The child of Family Three, a 7-year-old girl, manifested hematuria and proteinuria. Her mother, the proband of the family, was 34 years old, and manifested hematuria and proteinuria as well. The proband was diagnosed as IgAN by the same method used for Family Two. The girl's grandfather died of uremia at the age of 44. Genetic testing showed that the girl and her mother carried a heterozygous variant 539G>A (Gly180Glu)in COL4A5 gene. Conclusions: The variant of the CFHR5 gene identified in Family One is of uncertain signifance, and the two variants of the COL4A5 gene identified in Families Two and Three are pathogenic. The probands of Families Two and Three are diagnosed as Alport syndrome. The study suggests that clinicians should examine genetic variants of FH associated genes in families with hematuria when the probands were diagnosed as IgAN by their clinical manifestations, renal pathology and routine immunohistochemistry.

Overexpression of miR-770 indicates a favorable prognosis and suppresses tumorigenesis by modulating PI3K-AKT pathway in glioma.

OBJECTIVE: Previous studies showed that miR-770 expression was deregulated in many tumors. However, the effect of miR-770 function on glioma remains as a mystery. The present study aimed to explore its expression, cellular function and clinic features in glioma. PATIENTS AND METHODS: We analyzed RNA sequencing data to explore abnormally expressed miRNAs in glioma. Glioma tissue specimens and their matched normal tissues were collected to test miR-770 expression using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis. The correlation between miR-770 and the clinicopathological factors and the prognostic value of miR-770 was statistically analyzed. We then investigated alterations in a series of cancer-related phenotypes, including cell viability, apoptosis, colony formation and metastasis capacities. Western blot analysis was performed to examine the expression changes of EMT-related proteins and PI3K/Akt signaling pathway proteins. RESULTS: We identified a novel glioma-related miRNA miR-770, which was significantly down-regulated in human glioma tissues. The results of RT-PCR further showed that miR-770 expression was significantly down-regulated in both glioma tissues and cell lines. Furthermore, decreased miR-770 expression was significantly associated with advanced WHO grade, KPS score and shorter five-year overall survival. Then, functional assays indicated that overexpression of miR-770 suppressed proliferation, migration, invasion and EMT pathway, and induced the apoptosis of glioma cells in vitro. Moreover, we further illustrated that the up-regulation of miR-770 suppressed the PI3K-AKT signaling pathway. CONCLUSIONS: Our present findings firstly reported the roles and mechanisms associated with miR-770 in glioma progression, highlighting miR-770 as a potential therapeutic target for glioma patients.

MiR-203 over-expression promotes prostate cancer cell apoptosis and reduces ADM resistance.

OBJECTIVE: Extra-cellular signal regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway is widely involved in cell proliferation, apoptosis, and drug resistance. MAPK kinase 1 (MEK1) is the upstream protein kinase of ERK that can activate ERK/MAPK signaling pathway. microRNA 203 (MiR-203) down-regulation is found to be associated with prostate cancer pathogenesis. Bioinformatics analysis showed the complementary targeted relationship between miR-203 and the 3'-UTR of MEK1 mRNA. This study explored the role of miR-203 in regulating prostate cancer cell proliferation, apoptosis, and ADM resistance through affecting MEK1 expression. MATERIALS AND METHODS: Dual luciferase assay confirmed the targeted relationship between miR-203 and MEK1. MiR-203, MEK1, p-ERK1/2, and B cell lymphoma 2 (Bcl-2) expressions were compared in normal prostate epithelial cells PrEC, prostate cancer cells PC-3M, and drug resistance cells PC-3M/ADM. PC-3M, PC-3M/ADM cell apoptosis and proliferation were detected by using flow cytometry under ADM treatment at IC50 concentration of PC-3M cells. PC-3M cells were cultured in vitro and divided into four groups, including microRNA-normal control (miR-NC), miR-203 mimic, small interfere NC (si-NC), and si-MEK1. RESULTS: MiR-203 targeted and inhibited MEK1 expression. MiR-203 levels and cell apoptosis were significantly lower, while MEK1, p-ERK1/2, Bcl-2, and cell proliferation were significantly higher in PC-3M/ADM cells compared to the PC-3M cells. MiR-203 mimic and/or si-MEK1 transfection significantly reduced MEK1, p-ERK1/2, and Bcl-2 levels, attenuated cell proliferation, induced cell apoptosis, and decreased drug resistance. CONCLUSIONS: MiR-203 elevation suppressed prostate cancer PC-3M cell proliferation, promoted apoptosis, and weakened ADM resistance through targeted inhibiting MEK1 expression to alleviate ERK/MAPK signaling pathway and Bcl-2 expression.

[Focal segmental glomerulosclerosis after renal transplantation in a child with ANCA-associated glomerulonephritis: case report and literature review].

Objective: To study the clinical features and treatment of focal segmental glomerulosclerosis (FSGS) after renal transplantation in a child with ANCA-associated glomerulonephritis. Method: The clinical and pathological data of the patient treated in the Department of Pediatrics as well as in the Department of Organ Transplantation in November 2015 in the First Affiliated Hospital of Sun Yat-sen University, who was diagnosed with de novo FSGS after renal transplantation with a primary disease ANCA-associated glomerulonephritis, was analyzed retrospectively. Reports on "ANCA-associated glomerulonephritis" "(renal OR kidney) transplantation" "focal segmental glomerular sclerosis" were searched and reviewed. Result: A ten years old female was definitely diagnosed with ANCA-associated glomerulonephritis on the 81st day after the onset of primary ANCA associated glomerulonephritis. Because of progressive decline of renal function, a hemodialysis period for 7 months was administered following the pulsed methylprednisolone as well as cyclophosphamide treatment. The renal transplantation was then carried out 18 months later, the renal function recovered 7 days later while proteinuria reappeared 28 days after renal transplantation. Based on the anti-rejection treatment, 3 times pulsed methylprednisolone administration did not make difference on reducing the proteinuria and then a renal biopsy was conducted and the transplanted kidney proved to be a newly developed FSGS. Consequently, plasma exchange therapy was administrated. When the plasma exchange course finished, the proteinuria decreased significantly (from 3.270 g/24 h to 0.370 g/24 h). No reports were retrieved either in Chinese databases or at PubMed as well as Medline databases. Conclusion: FSGS appears in transplanted kidney in patient with a primary renal disease as ANCA associated glomerulonephritis with early proteinuria after transplantation as well as negative P-ANCA and MPO. Pathology of renal biopsy revealed FSGS while the pathology of other recipient was not FSGS. The patient had no response to pulsed methylprednisolone therapy. Instead, plasma exchange therapy was an alternative also effective treatment for de novo FSGS in transplanted kidney.

[A meta-analysis of HIV seroprevalence in pregnant women with syphilis and the impact of syphilis infection on mother-to-child HIV transmission].

Objective: To estimate HIV seroprevalence among pregnant women with syphilis and evaluate the influence of syphilis infection on mother-to-child-transmission (MTCT) of HIV by meta-analysis. Methods: We conducted a systematic literature search for 1 678 articles related to maternal syphilis and HIV infection published until October 1st 2015 using the PubMed, Web of Science, Chinese Web of Knowledge, Wanfang, Weipu, and SinoMed databases and evaluated the quality of each papers using the STROBE checklist, and the keywords were " pregnant women/maternal/pregnancy" , "syphilis/AIDS" , "HIV/human immunodeficiency virus" , "mother- to-child transimission/vertical transmission" . Excluding studies with the special subgroups of HIV-positive pregnant women as the research objects, review or meeting abstract, impossibility of full-text acquisition, sample size <50, duplication or impossibility of data extraction, finally, 16 studies were included. Random-effects meta-analysis was used to estimate HIV seroprevalence among pregnant women with syphilis and the RR of MTCT for women infected with both syphilis and HIV. Subgroup analyses were undertaken by study location, sample size, use of anti-retroviral therapy and study quality. Results: Sixteen studies with a combined sample of 110 573 pregnant women were included in the analysis. Of these, ten reported HIV seroprevalences among pregnant women with syphilis and six studies evaluated the influence of syphilis infection on MTCT of HIV. Pooled estimates yielded a HIV seroprevalence of 11.6% (95% CI: 6.7%-19.5%) among pregnant women with syphilis. We estimated that the risk of MTCT of HIV was 1.86 times (RR=1.86, 95% CI: 0.89%-3.89%) higher among pregnant women with syphilis compared with those only infected with HIV-although this effect was not statistically significant. Cochran's Q test showed a high degree of heterogeneity in estimates of HIV seroprevalence and the effect of syphilis infection on MTCT of HIV across studies (I2=89.4% and 86.2%, respectively, P<0.10). Subgroup analysis estimated HIV seroprevalences of 24.9% (95%CI: 17.4%-34.3%) in Africa, 2.8% (95% CI: 1.4%-5.6%) in Asia and 2.2% (95% CI: 0.7%-6.7%) in South America. While studies with a large sample size (≥100) or of higher quality estimated overall seroprevalence at 15.2% (95%CI: 9.0%-24.7%), this was 2.2% (95%CI: 0.7%-6.7%) for lower-quality or smaller studies. Meanwhile, subgroup analyses of the RR of MTCT of HIV in pregnant women infected both with HIV and syphilis gave estimates of 1.19 (0.62-2.29) for the higher quality studies, 4.76 (2.65-8.53) for the lower-quality studies, 1.47 (0.77-2.81) for studies with a large sample size, 5.82 (3.16-10.74) for studies with a small sample size, 4.76 (2.65-8.53) for studies in which participants received antiretroviral treatment and 1.19 (0.62-2.29) for studies in which they did not. While Begg's test showed evidence of publication bias in studies of HIV seroprevalence estimates in pregnant women with syphilis (t=-2.48, P=0.038), no evidence of publication bias was found in studies on the influence of syphilis infection on MTCT of HIV (t=-0.22, P=0.835). Conclusion: HIV seroprevalence is higher among pregnant women with syphilis than uninfected women. Further research is warranted to verify whether syphilis infection can increase the risk of MTCT of HIV.

[Endovascular implantation of iodine-125 seeds strand and portal vein stenting followed by transcatheter arterial chemoembolization combined therapy with sorafenib for hepatocellular carcinoma with main portal vein tumor thrombus].

OBJECTIVE: To compare the therapeutic effect of portal vein stenting and endovascular implantation of iodine-125 seeds strand followed by transcatheter arterial chemoembolization combined with or without sorafenib in patients for hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (MPVTT). METHODS: A total of 53 patients with HCC complicated by MPVTT who received portal vein stenting and endovascular implantation of iodine-125 seeds strand followed by transcatheter arterial chemoembolization combined without (group A, n=38) or with (group B, n=15) sorafenib in Affiliated Yancheng Hospital of Southeast University Medical College during January 2010 and August 2015 were analyzed retropectively.Overal survival, progress free survival and procedure-related adverse event were compared between the two groups. RESULTS: The technical success rate was 100% for placement of (125)I seeds strand and stent in the obstructed main portal vein.No serious procedure-related adverse events occurred. Median survival time of group A and B were 12.1 and 14.8 months, respectively (P=0.037). Additionally, Median progress free survival time of group A and B were 2.8 and 4.0 months, respectively (P=0.002). CONCLUSIONS: Endovascular implantation of iodine-125 seeds strand and portal vein stenting followed by transcatheter arterial chemoembolization combined with sorafenib could improve the survival time, the progress free survival time of patients with HCC complicated by MPVTT.

Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up.

Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This non-randomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10(6) cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4- and CD8- positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).

Relaxin inhibits cardiac fibrosis and endothelial-mesenchymal transition via the Notch pathway.

BACKGROUND: Relaxin (RLX) can prevent cardiac fibrosis. We aimed to investigate the possible mechanism and signal transduction pathway of RLX inhibiting cardiac fibrosis. METHODS: Isoproterenol (5 mg·kg(-1)·d(-1)) was used to establish the cardiac fibrosis model in rats, which were administered RLX. The cardiac function, related targets of cardiac fibrosis, and endothelial-mesenchymal transition (EndMT) were measured. Transforming growth factor ß (TGF-ß) was used to induce EndMT in human umbilical vein endothelial cells, which were pretreated with RLX, 200 ng·mL(-1), then with the inhibitor of Notch. Transwell cell migration was used to evaluate cell migration. CD31 and vimentin content was determined by immunofluorescence staining and Western blot analysis. Notch protein level was examined by Western blot analysis. RESULTS: RLX improved cardiac function in rats with cardiac fibrosis; it reduced the content of collagen I and III, increased the microvascular density of the myocardium, and suppressed the EndMT in heart tissue. In vitro, RLX decreased the mobility of human umbilical vein endothelial cells induced by TGF-ß, increased the expression of endothelial CD31, and decreased vimentin content. Compared to TGF-ß and RLX co-culture alone, TGF-ß + RLX + Notch inhibitor increased cell mobility and the EndMT, but decreased the levels of Notch-1, HES-1, and Jagged-1 proteins. CONCLUSION: RLX may inhibit the cardiac fibrosis via EndMT by Notch-mediated signaling.

High prevalence of type 41 and high sequence diversity of partial hexon gene of human adenoviruses in municipal raw sewage and activated sludge.

AIM: This study was aimed to assess seasonal/geographical distribution and sequence diversity of partial hexon gene for human adenoviruses (HAdVs) within raw sewages (RS) and activated sludges (AS). METHODS AND RESULTS: Assessments were based on high-throughput sequencing (HTS) for polymerase chain reaction (PCR)-amplified 128-bp partial hexon gene fragments and followed by principal coordinate analyses (PCoA) for revealed sequences. Sequencing results showed that the majority of sequences (>90%) for the RS or AS samples were identical to HAdV type 41 of species F, while rest of few sequences belonged to HAdV species-D and -C were only occurred rarely without significant seasonal/geographical variation. The partial hexon genes were highly diverse as many sequence types and operational taxonomic unit groups were noticed among the matched sequences. CONCLUSIONS: This study demonstrated that HAdV-41 was constantly appeared in the RS and AS samples from Taiwan throughout the year without significant seasonal or geographical variations; but, had high sequence diverse noticed for the 128-bp partial hexon gene fragments. SIGNIFICANCE AND IMPACT OF THE STUDY: High-throughput-sequencing results provided better insights of HAdV distribution and genetic diversity for raw sewage and AS samples allowing some probable biases for cloning-sequencing approach to be defeated and further providing public health awareness regarding viral-contaminated sewages or sludges.