A Novel Nomogram to Predict Prognosis of Advanced Hepatocellular Carcinoma Treated with Intensity-Modulated Radiotherapy Plus Anti-PD1.

Purpose: The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti-PD1) showed preliminary efficacy in hepatocellular carcinoma (HCC). This study aimed to identify the prognostic factors and construct a nomogram to predict the overall survival (OS) of patients with advanced HCC after treatment with intensity-modulated radiotherapy (IMRT) plus anti-PD1. Patients and Methods: The OS and progression-free survival (PFS) of 102 patients with BCLC stage C HCC was analyzed using the Kaplan-Meier method. Potential independent prognostic factors were determined using univariate and multivariate Cox regression analyses. A nomogram was established to predict prognosis whose accuracy and reliability was verified by a calibration curve and area under the receiver operating characteristic curve (AUROC). Results: The median PFS and OS rates of the 102 patients with advanced HCC were 9.9 months and 14.3 months, respectively. Ninety-three patients were evaluated for efficacy, including five (5.38%) with complete response and 48 (51.61%) with partial response, with an overall response rate of 56.99%. Grade 3 and 4 adverse reactions (AEs) were observed in 32.35% of patients; no grade 5 AEs occurred. Multivariate Cox analysis revealed albumin and alpha-fetoprotein levels, neutrophil counts 3-4 weeks after IMRT initiation, and platelet-to-lymphocyte ratio 3-4 weeks after IMRT initiation to be independent prognostic factors. The nomogram model constructed using these factors had good consistency and accuracy with 1-3 years AUROC of 78.7, 78.6, and 93.5, respectively. Conclusion: IMRT plus anti-PD1 showed promising efficacy and controllable adverse reactions in treating advanced HCC. The nomogram model demonstrated good reliability and clinical applicability.

The combination of radiotherapy and monoclonal antibody against programmed cell death 1 (anti­PD1) showed preliminary efficacy and manageable safety in HCC. We retrospectively evaluated the efficacy and safety of 102 patients with advanced HCC treated with intensity-modulated radiotherapy (IMRT) plus anti-PD1. The study shows that the combination showed promising efficacy with a median PFS and OS of 9.9 months and 14.3 months, respectively. The adverse reactions were controllable. The novel nomogram model established based on independent prognostic factors including albumin, alpha-fetoprotein, neutrophils count 3­4 weeks after IMRT initiation and platelet-to-lymphocyte ratio 3­4 weeks after IMRT initiation demonstrated good reliability.

Therapeutic potential of dihydroartemisinin in mitigating radiation-induced lung injury: Inhibition of ferroptosis through Nrf2/HO-1 pathways in mice.

BACKGROUND: Radiation-induced lung injury (RILI) is a common consequence of thoracic radiation therapy that lacks effective preventative and treatment strategies. Dihydroartemisinin (DHA), a derivative of artemisinin, affects oxidative stress, immunomodulation, and inflammation. It is uncertain whether DHA reduces RILI. In this work, we investigated the specific mechanisms of action of DHA in RILI. METHODS: Twenty-four C57BL/6J mice were randomly divided into four groups of six mice each: Control group, irradiation (IR) group, IR + DHA group, and IR + DHA + Brusatol group. The IR group received no interventions along with radiation treatment. Mice were killed 30 days after the irradiation. Morphologic and pathologic changes in lung tissue were observed with hematoxylin and eosin staining. Detection of hydroxyproline levels for assessing the extent of pulmonary fibrosis. Tumor necrosis factor α (TNF-α), transforming growth factor-ß (TGF-ß), glutathione peroxidase (GPX4), Nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) expression in lung tissues were detected. In addition, mitochondrial ultrastructural changes in lung tissues were also observed, and the glutathione (GSH) content in lung tissues was assessed. RESULTS: DHA attenuated radiation-induced pathological lung injury and hydroxyproline levels. Additionally, it decreased TNF-α and TGF-ß after irradiation. DHA may additionally stimulate the Nrf2/HO-1 pathway. DHA upregulated GPX4 and GSH levels and inhibited cellular ferroptosis. Brusatol reversed the inhibitory effect of DHA on ferroptosis and its protective effect on RILI. CONCLUSION: DHA modulated the Nrf2/HO-1 pathway to prevent cellular ferroptosis, which reduced RILI. Therefore, DHA could be a potential drug for the treatment of RILI.

Development and validation of a nomogram for radiation-induced hepatic toxicity after intensity modulated radiotherapy for hepatocellular carcinoma: a retrospective study.

OBJECTIVE: This study aimed to construct a nomogram to predict radiation-induced hepatic toxicity in patients with hepatocellular carcinoma treated with intensity-modulated radiotherapy. METHODS: This study reviewed the clinical characteristics and dose-volume parameters of 196 patients with hepatocellular carcinoma. Radiation-induced hepatic toxicity was defined as progression of the Child-Pugh score caused by intensity-modulated radiotherapy. Factors relevant to radiation-induced hepatic toxicity were selected using receiver operating characteristic and univariate logistic analysis. A risk assessment model was developed, and its discrimination was validated. RESULTS: Eighty-eight (44.90%) and 28 (14.29%) patients had radiation-induced hepatic toxicity ≥ 1 (Child-Pugh ≥ 1) and radiation-induced hepatic toxicity ≥ 2 (Child-Pugh ≥ 2). Pre-treatment Child-Pugh, body mass index and dose-volume parameters were correlated with radiation-induced hepatic toxicity ≥ 1 using univariate logistic analysis. V15 had the best predictive effectiveness among the dose-volume parameters in both the training (area under the curve: 0.763, 95% confidence interval: 0.683-0.842, P < 0.001) and validation cohorts (area under the curve: 0.759, 95% confidence interval: 0.635-0.883, P < 0.001). The area under the curve values of the model that was constructed by pre-treatment Child-Pugh, body mass index and V15 for radiation-induced hepatic toxicity ≥1 were 0.799 (95% confidence interval: 0.719-0.878, P < 0.001) and 0.775 (95% confidence interval: 0.657-0.894, P < 0.001) in the training and validation cohorts, respectively. Patients with a body mass index ≤ 20.425, Barcelona clinic liver cancer = C, Hepatitis B Virus-positive, Eastern Cooperative Oncology Group = 1-2 and hepatic fibrosis require lower V15 dose limits. CONCLUSIONS: Risk assessment model constructed from Pre-treatment Child-Pugh, V15 and body mass index can guide individualized patient selection of toxicity minimization strategies.

Adjuvant chemotherapy or no adjuvant chemotherapy? A prediction model for the risk stratification of recurrence or metastasis of nasopharyngeal carcinoma combining MRI radiomics with clinical factors.

BACKGROUND: Dose adjuvant chemotherapy (AC) should be offered in nasopharyngeal carcinoma (NPC) patients? Different guidelines provided the different recommendations. METHODS: In this retrospective study, a total of 140 patients were enrolled and followed for 3 years, with 24 clinical features being collected. The imaging features on the enhanced-MRI sequence were extracted by using PyRadiomics platform. The pearson correlation coefficient and the random forest was used to filter the features associated with recurrence or metastasis. A clinical-radiomics model (CRM) was constructed by the Cox multivariable analysis in training cohort, and was validated in validation cohort. All patients were divided into high- and low-risk groups through the median Rad-score of the model. The Kaplan-Meier survival curves were used to compare the 3-year recurrence or metastasis free rate (RMFR) of patients with or without AC in high- and low-groups. RESULTS: In total, 960 imaging features were extracted. A CRM was constructed from nine features (seven imaging features and two clinical factors). In the training cohort, the area under curve (AUC) of CRM for 3-year RMFR was 0.872 (P <0.001), and the sensitivity and specificity were 0.935 and 0.672, respectively; In the validation cohort, the AUC was 0.864 (P <0.001), and the sensitivity and specificity were 1.00 and 0.75, respectively. Kaplan-Meier curve showed that the 3-year RMFR and 3-year cancer specific survival (CSS) rate in the high-risk group were significantly lower than those in the low-risk group (P <0.001). In the high-risk group, patients who received AC had greater 3-year RMFR than those who did not receive AC (78.6% vs. 48.1%) (p = 0.03). CONCLUSION: Considering increasing RMFR, a prediction model for NPC based on two clinical factors and seven imaging features suggested the AC needs to be added to patients in the high-risk group and not in the low-risk group.

Nestin+ Mesenchymal Stromal Cells Fibrotic Transition Mediated by CD169+ Macrophages in Bone Marrow Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) involves multiple organs, but little is known about bone marrow (BM) alterations caused by cGVHD. In mice and humans, we found that cGVHD is associated with BM fibrosis resulting in T cell infiltration, IgG deposition, and hematopoietic dysfunction. Macrophages and Nestin+ mesenchymal stromal cells (MSCs) participated in the process of BM fibrosis during BM cGVHD development. BM macrophage numbers were significantly increased in mice and humans with BM fibrosis associated with cGVHD. Amplified macrophages produced TGF-ß1, which recruited Nestin+ MSCs forming clusters, and Nestin+ MSCs later differentiated into fibroblasts, a process mediated by increased TGF-ß/Smad signaling. TLR4/MyD88-mediated activation of endoplasmic reticulum (ER) stress in macrophages is associated with fibrosis by increasing Nestin+ MSC migration and differentiation into fibroblasts. Depletion of macrophages by clodronate-containing liposomes and inhibition of ER stress by 4-phenylbutyric acid reversed BM fibrosis by inhibiting fibroblast differentiation. These studies provide insights into the pathogenesis of BM fibrosis during cGVHD development.

Ruxolitinib versus basiliximab for steroid-refractory acute graft-versus-host disease: a retrospective study.

Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation; not all patients respond to standard glucocorticoids treatment. This study retrospectively evaluated the effects of ruxolitinib compared with basiliximab for steroid-refractory aGVHD (SR-aGVHD). One hundred and twenty-nine patients were enrolled, 81 in ruxolitinib and 48 in basiliximab group. The overall response (OR) at day 28 was higher in ruxolitinib group (72.8% vs. 54.2%, P = 0.031), as with complete response (CR) (58.0% vs. 35.4%, P = 0.013). Ruxolitinib led to significantly lower 1-year cumulative incidence of chronic GVHD (cGVHD) (29.6% vs. 43.8%, P = 0.021). Besides, ruxolitinib showed higher 1-year overall survival (OS) and 1-year cumulative incidence of failure-free survival (FFS) (OS: 72.8% vs. 50.0%, P = 0.008; FFS: 58.9% vs. 39.6%, P = 0.014). The 1-year cumulative incidence of non-relapse mortality (NRM) was lower in ruxolitinib group (16.1% vs. 37.5%, P = 0.005), and the 1-year relapse was not different. The 1-year cumulative incidence of cytomegalovirus (CMV) viremia, CMV-associated diseases and Epstein-Barr virus (EBV)-associated diseases was similar between the two groups, but EBV viremia was significantly lower in ruxolitinib group (6.2% vs. 29.2%, P < 0.001). Subgroup analyses revealed that OR and survival were similar in ruxolitinib 5 mg twice daily (bid) and 10 mg bid groups. However, ruxolitinib 10 mg bid treatment markedly reduced 1-year cumulative incidence of cGVHD compared with 5 mg bid (21.1% vs. 50.0%, P = 0.016). Our study demonstrated that ruxolitinib was superior to basiliximab in SR-aGVHD treatment and cGVHD prophylaxis, therefore should be recommended.

[Physiological regulation of salicylic acid on Helianthus tubeuosus upon copper stress and root FTIR analysis].

Phytoremediation plays an important role in the treatment of heavy metal pollution in soil. In order to elucidate the mechanism of salicylic acid (SA) on copper absorption, seedlings from Xuzhou (with strong Cu-tolerance) and Weifang Helianthus tuberosus cultivars (with weak Cu-tolerance) were selected for pot culture experiments. 1 mmol/L SA was sprayed upon 300 mg/kg soil copper stress, and the photosynthesis, leaf antioxidant system, several essential mineral nutrients and the changes of root upon copper stress were analyzed to explore the mechanism of copper resistance. The results showed that Pn, Tr, Gs and Ci upon copper stress decreased significantly compared to the control group. Meanwhile, chlorophyll a, chlorophyll b and carotenoid decreased with significant increase in initial fluorescence (F0), maximum photochemical quantum yield of PSⅡ (Fv/Fm), electron transfer rate (ETR) and photochemical quenching coefficient (qP) content all decreased. The ascorbic acid (AsA) content was decreased, the glutathione (GSH) value was increased, the superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in the leaves were decreased, and the peroxidase (POD) activity was significantly increased. SA increased the Cu content in the ground and root system, and weakened the nutrient uptake capacity of K, Ca, Mg, and Zn in the root stem and leaves. Spray of exogenous SA can maintain the opening of leaf stomata, improve the adverse effect of copper on photosynthetic pigment and PSⅡ reaction center. Mediating the SOD and APX activity started the AsA-GSH cycle process, effectively regulated the antioxidant enzyme system in chrysanthemum taro, significantly reduced the copper content of all parts of the plant, and improved the ion exchange capacity in the body. External SA increased the content of the negative electric group on the root by changing the proportion of components in the root, promoted the absorption of mineral nutrient elements and the accumulation of osmoregulatory substances, strengthened the fixation effect of the root on metal copper, and avoided its massive accumulation in the H. tuberosus body, so as to alleviate the inhibitory effect of copper on plant growth. The study revealed the physiological regulation of SA upon copper stress, and provided a theoretical basis for planting H. tuberosus to repair soil copper pollution.

Cyclin B1 expression as an independent prognostic factor for lung adenocarcinoma and its potential pathways.

Although great progress has been made in the early diagnosis and targeted therapy of lung adenocarcinoma (LUAD), the survival of patients with LUAD remains unsatisfactory. There is an urgent requirement for new biomarkers to guide the diagnosis, prognosis and treatment of LUAD. Following an initial bioinformatics screen, the present study focused on cyclin B1 (CCNB1) in LUAD. A total of 94 patients with LUAD from a single hospital were included in the study. CCNB1 protein expression was detected and scored in 94 LUAD samples and 30 normal tissue samples by immunohistochemistry. The associations between CCNB1 expression and the clinicopathological features of the patients with LUAD were analyzed. Furthermore, the relationship between prognosis and the CCNB1 expression level was analyzed using Cox regression and survival analyses. Weighted gene co-expression network analysis and RNA-sequencing were also applied to identify the potential molecular mechanisms of CCNB1 in LUAD. CCNB1 was highly expressed in patients with LUAD and was associated with poor prognosis. It may affect the expression of CPLX1, PPIF, SRPK2, KRT8, SLC20A1 and CBX2 genes and function via different pathways. CCNB1 has the potential to become a novel prognostic target for LUAD.

Distribution of CD8 T Cells and NK Cells in the Stroma in Relation to Recurrence or Metastasis of Nasopharyngeal Carcinoma.

Objective: The purpose of this study was to explore the expression and distribution of tumor-infiltrating immune cells (TIICs) and their relationship with recurrence and metastasis of nasopharyngeal carcinoma (NPC). Methods: The gene expression profiles of NPC were downloaded from GEO database (GSE53819 and GSE64634). The abundance of TIICs in NPC samples was calculated by the CIBERSORT algorithm, and TIICs with higher expression were screened in NPC. Then, we performed immunohistochemistry experiments to evaluate the expression of selected TIICs in 94 NPC samples from the Affiliated Hospital of Zunyi Medical University. We further explored the relationship between TIICs and recurrence and metastasis of NPC. Results: The results based on the GEO database showed that the expression of CD8 T cells, NK cells, macrophages and plasma cells was higher than that in normal tissues. Immunohistochemistry results showed that CD8 T cells, NK cells, macrophages and plasma cells were mainly expressed in the stroma, and the expression of CD8 T cells and NK cells in the stroma of patients without recurrence or metastasis was significantly higher than that in patients with recurrence or metastasis of NPC. Kaplan-Meier analysis showed that patients with high CD8 T cells and high NK cells expression in the stroma had favorable recurrence or metastasis-free survival and overall survival (P<0.05). Univariate and multivariate Cox analyses indicated that CD8 T cells and NK cells in the stroma were independent factors for the recurrence or metastasis of NPC. Conclusion: The expression of CD8 T cells, NK cells, macrophages and plasma cells is significantly higher than that in normal tissues. Among them, the expression of CD8 T cells and NK cells is closely related to the recurrence and metastasis of NPC. They are independent factors affecting the recurrence and metastasis of NPC.

Efficacy of endoscopic resection and intensity-modulated radiotherapy for thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: a case report.

Background: Among the malignant tumors that occur in the nasopharynx, nasopharyngeal carcinoma is the most common. Nasopharyngeal carcinoma (NPC) is commonly diagnosed in Southeastern Asia, particularly in southern China. It originates from the epithelial lining of the nasopharynx and has a variety of pathological subtypes. The vast majority of NPC cases are keratinizing or nonkeratinizing squamous cell carcinoma. Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is an extremely rare malignant tumor. Most reports regarding this disease mainly focus on clinical diagnosis and pathology; however, reports regarding therapy and follow-up are relatively limited. The case in the study presents a female patient with LGNPPA. The patient underwent endoscopic resection and adjuvant radiotherapy. Following-up 6 years, the patient was free of local recurrence and distant metastasis. Because of the very low incidence, there are no guidelines or protocols developed for proper, standardized therapy, we aim to provide useful recommendations regarding optimal treatment strategies by exploring the therapeutic expectancies of the rare disease. Case Description: A 45-year-old female of Han ethnicity visited a local hospital for over 2 years of recurrent nasal congestion. The patient had no previous medical history, had a history of smoking (6 years, 20 cigarettes per day) and drank occasionally. but had no family history of cancer. Epstein-Barr virus (EBV) DNA was <500×102 IU/mL. Based on findings from computed tomography (CT) scans of the nasal cavity and paranasal sinuses, nasal endoscopy, and postoperative pathology, the diagnosis was low-grade papillary adenocarcinoma located at the upper nasopharynx (T1N0M0, stage I). This patient underwent endoscopic resection. After the endoscopic resection, she received intensity-modulated radiotherapy. After radiotherapy, there was no residual by nasopharyngo-fiberoscope. And she was free of local recurrence and distant metastasis at 6 years of follow-up. Conclusions: Although primary nasopharyngeal adenocarcinomas (NPACs) are very rare, they also should be pay attention to. As far as treatment policy, no standard treatment exists for the tumors. So through this case report, we want to provide a possible useful recommendations regarding optimal treatment strategies by exploring the therapeutic expectations of this rare disease.

Successful treatment of two patients with unresectable lung squamous cell carcinoma with tislelizumab regardless of programmed death-ligand 1 expression: a report of two cases.

Since the treatment of lung squamous cell carcinoma (SCC) was limited due to a lack of appropriate biomarkers and novel target agents. Immune checkpoint inhibitors can offer an effective treatment for patients with advanced non-small cell lung cancer. Here, we described the cases of two patients with SCC who showed a good response following treatment with tislelizumab. We encountered two patients with unresectable lung SCC who were treated with immunotherapy and chemotherapy. One patient had negatively programmed death-ligand 1 expression, and the primary lesion becomes a thick wall cavity after the tislelizumab combined with chemotherapy. Another patient was diagnosed with advanced lung SCC with negative programmed death-ligand 1 expression. After the treatment, the fluorine-18-fluorodeoxyglucose PET/computed tomography indicated that no abnormal increase in radioactivity uptake and tend to complete remission. We found a significant response or even complete response in unresectable SCC treated with tislelizumab combined with chemotherapy. Our cases added evidence of the feasibility and efficacy of tislelizumab combined with chemotherapy in unresectable lung SCC.

Network Pharmacology-Based Approach to Investigate the Molecular Targets of Sinomenine for Treating Breast Cancer.

PURPOSE: Sinomenine has been known to inhibit the proliferation of breast cancer cells. However, its targets have not been found yet. This study aimed to search for molecular targets of sinomenine for treating breast cancer via network pharmacology. METHODS: Potential targets of sinomenine or breast cancer were separately screened from indicated databases. The common targets of both sinomenine and breast cancer were considered as the targets of sinomenine for treating breast cancer. A sinomenine-target-pathway network was constructed based on the obtained results from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The putative targets of sinomenine were further determined by using protein-protein interaction (PPI) analysis and molecular docking. Finally, the putative targets were verified in vitro and in vivo. RESULTS: Twenty predicted targets were identified through network pharmacological analysis. Gene Ontology (GO) and KEGG pathway enrichment indicated that these predicted targets enriched in the process of MAP kinase activity, VEGF signaling pathway, Relaxin signaling pathway, Growth hormone synthesis, secretion and action. MAPK1, NOS3, NR3C1, NOS1 and NOS2 were further identified as the putative targets by using PPI and molecular docking analysis. Expression of MAPK1, NR3C1, NOS1, NOS2 and NOS3 genes were significantly regulated by sinomenine in both MCF-7 cells and MDA-MB-231 cells. Furthermore, the expression of NR3C1 in human breast cancer specimens was lower than that in para-tumor normal tissues. Meanwhile, the expression of NR3C1 in xenograft tumors was up-regulated after sinomenine treatment. CONCLUSION: MAPK1, NR3C1, NOS1, NOS2 and NOS3 were identified as the putative targets of sinomenine for treating breast cancer. NR3C1 was preliminarily confirmed as a target of sinomenine in two breast cancer cell lines, xenograft tumor models and human breast cancer specimens. These data indicated that the network pharmacology-based prediction of sinomenine targets for treating breast cancer could be reliable.

Prevalence and genotype distribution of HPV and cervical pathological results in Sichuan Province, China: a three years surveys prior to mass HPV vaccination.

BACKGROUND: HPV persistent infection is a strong carcinogenic factor that can induce cervical cancer. Investigation of HPV epidemiology and genotype distribution is of great meaning for the development of cervical cancer prevention and control strategies. METHODS: By using PCR-based hybridization gene chip assay, HPV genotype was detected from 14,185 women that came from HEC (Health Examination Center) or OGOC (Obstetrics and Gynecology Outpatient Clinics) between 2015 and 2017 in Sichuan area. The epidemiology and genotype distribution as well as the relationship between HPV infection and histology/cytology abnormalities were analyzed. RESULTS: The positivity rate of HPV was 23.84%. The HPV-positive rate of OGOC group (37.62%) was significantly higher than that of HEC group (15.29%), p < 0.05. The prevalence of HPV reached peak at age 41-50 (5.86%) in HEC group, but at age 21-30 (14.74%) in OGOC group. Of all the HPV positive women, single genotype infection was the most common form in both HEC and OGOC group (62.06% in total screening population, 74.36% in HEC group and 54.01% in OGOC group). Three most prevalent HPV types were HPV-52 (5.02%), 58 (3.61%), and 16 (3.24%) in total screening population. Of all the HPV positive women, the top three types were HPV-52 (20.93%), CP8304 (15.32%), and 58 (14.42%) in HEC group, while were HPV-52 (21.14%), 16 (16.34%), and 58 (15.61%) in OGOC group. HPV 52/16/58 accounted for 41.84% of cytology and 56.52% of histological abnormalities. CONCLUSIONS: Women in Sichuan area were facing the great threat of HPV infection, especially the women aged between 21 ~ 30 or 41-50 years old. The priority HPV types were HPV 52, 58, and 16 in OGOC group, while were HPV 52, CP8304, and 58 in HEC group. HPV 52/16/58 accounted for the majority of cytology and histological abnormalities. Our analysis was found to be valuable for providing a scientific basis for the prevention and control strategies of cervical cancer in Sichuan area.

Chronic kidney disease after autologous stem cell transplantation: analysis of a single center experience.

PURPOSE: Chronic kidney disease (CKD) after allogeneic hematopoietic stem cell transplantation (HSCT) has increasingly been reported. However, CKD after autologous HSCT, especially changes in renal pathology, has rarely been reported. This study aimed to evaluate the frequency of CKD among patients who received autologous HSCT for hematological and nonhematological disorders, and analyze its clinical and pathological features. METHODS: We performed a retrospective study to evaluate the frequency of CKD after autologous HSCT and analyzed clinical and pathological features of CKD. Clinical records of patients who underwent autologous HSCT at the First Affiliated Hospital of Guangxi Medical University between May 2000 and November 2010 were screened. Clinical data of those with kidney injury on presentation and follow-up were acquired from hospital records. RESULTS: A total of 41 patients who received autologous HSCT were identified. CKD developed in six patients (14.6%). Among the six patients, all had various degrees of proteinuria and three patients had nephrotic syndrome. Impaired renal function occurred in three patients. Three patients with nephrotic syndrome received only prednisone. Two patients obtained complete remission, and one had partial remission. What is particularly worth mentioning is, in two patients who received renal biopsy in our study, the pathological changes were mesangial proliferative glomerulonephritis. CONCLUSIONS: Mesangial proliferative glomerulonephritis may not be as uncommon as previously thought in CKD patients after autologous HSCT. Presentation of nephrotic syndrome is common in CKD after HSCT and prednisone alone are effective.

Effect of statins on chronic inflammation and nutrition status in renal dialysis patients: a systematic review and meta-analysis.

AIM: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may have an adjunctive effect on chronic inflammation and nutrition status in renal dialysis patients. Therefore, we performed a systematic review of randomized controlled trials to assess the effect of statins on chronic inflammation and nutrition status in dialysis patients. METHODS: The randomized controlled trials (RCTs) of statins versus placebo or no treatment for renal dialysis patients were searched from PubMed, EMbase and Cochran Central Register of Controlled Trials. We screened relevant studies according to predefined inclusion and exclusion criteria, evaluated the quality of the included studies, and performed meta-analyses by using the Cochrane Collaboration's Revman 5.1 software. RESULTS: We identified nine trials including 3098 patients. Meta-analysis showed statins can significantly decrease the serum C-reactive protein (CRP) (SMD, -0.54; 95% confidence interval (CI), -1.04 to -0.05; P = 0.03) and high sensitivity CRP (hs-CRP) level (SMD, -0.72; 95% CI, -1.14 to -0.31; P = 0.0007) of dialysis patients compared with that of the control group. However, statins did not differ significantly from the control group in increasing the serum Alb level (SMD, -0.13; 95% CI, -0.42 to 0.15; P = 0.37). CONCLUSIONS: Statins can improve the chronic inflammation status reflected by the decreasing of serum CRP and hs-CRP levels, whereas there is no conclusive evidence that it can improve the nutrition status. However, this result needs to be further confirmed in more high-quality randomized clinical trials.

Ectopic expression of Ligand-of-Numb protein X promoted TGF-beta induced epithelial to mesenchymal transition of proximal tubular epithelial cells.

Ligand-of-Numb protein X (LNX) was initially characterized as a RING finger type E3 ubiquitin ligase that targeted the intrinsic cell fate determinant Numb for ubiquitination dependent degradation. However, the physiological function of LNX remains largely unknown. In the present study, we demonstrate that ectopic expression of LNX in human proximal tubular epithelial cells (HK-2 cells) significantly enhanced TGF-beta1 induced epithelial to mesenchymal transition (EMT). The EMT-promoting effect of LNX manifested as strong inhibition of E-cadherin expression, enhanced expression of vimentin, fibronectin or PAI-1, and increased cell migration. This function of LNX was shown to be independent of its ligase activity because ectopic expression of a mutant form of LNX (C48ALNX) that lacks E3 ligase activity had the similar effect as the wild-type LNX. Overexpression of E-cadherin could inhibit LNX augmented EMT. This study suggests a potential role for LNX in promoting EMT in human proximal tubular epithelial cells.