Neoadjuvant Immunotherapy and Non-Small Cell Lung Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVES: To systematically evaluate the effectiveness and safety of neoadjuvant immunotherapy for patients with non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials of neoadjuvant immunotherapy in treating patients with NSCLC were comprehensively retrieved from electronic databases, eligible studies, previous systematic reviews and meta-analyses, guidelines, and conference abstracts. The meta-analysis was performed by the Stata/SE 12.0 software. RESULTS: Eleven randomized controlled trials were eventually included. The results of the meta-analysis showed that neoadjuvant immunochemotherapy significantly improved the objective response rate compared with neoadjuvant chemotherapy (CT; 62.46% vs 41.88%, P = 0.003), but the objective response rate of neoadjuvant double-immunotherapy was roughly comparable to that of neoadjuvant single-immunotherapy (15.74% vs 10.45%, P = 0.387). Major pathologic response (MPR) rate and pathologic complete response (pCR) rate of neoadjuvant immunochemotherapy and neoadjuvant double-immunotherapy were significantly superior to neoadjuvant CT alone and neoadjuvant single-immunotherapy, respectively. Compared with neoadjuvant CT alone, neoadjuvant immunochemotherapy increased the down-staging rate (40.16% vs 26.70%, P = 0.060), the surgical resection rate (83.69% vs 73.07%, P = 0.231), and R0 resection rate (86.19% vs 77.98%, P = 0.502), but there were no statistically significant differences. Neoadjuvant immunochemotherapy did not increase the postoperative complications rate than neoadjuvant CT alone (40.20% vs 41.30%, P = 0.920). In terms of safety, neoadjuvant immunochemotherapy and neoadjuvant double-immunotherapy did not increase the incidence of treatment-related adverse events (TRAEs) and the grade 3 or higher TRAEs. CONCLUSIONS: In summary, neoadjuvant immunochemotherapy had better clinical efficacy than neoadjuvant CT for patients with NSCLC. MPR rate and pCR rate of neoadjuvant immunochemotherapy and neoadjuvant double-immunotherapy were significantly superior to neoadjuvant CT and neoadjuvant single-immunotherapy, respectively, for patients with NSCLC, showing that MPR rate and pCR rate were probably considered as alternative endpoints for survival benefit. TRAEs were comparable between the corresponding groups. The long-term survival outcome of neoadjuvant immunotherapy for patients with NSCLC needs to be further confirmed to better guide clinical practice.

Gum arabic as a sole wall material for constructing nanoparticle to enhance the stability and bioavailability of curcumin.

In this study, a kind of nanoparticle prepared using gum arabic as a sole wall material for loading curcumin was obtained. The properties and digestive characteristics of the curcumin-loaded nanoparticle were determined. Results showed that the maximum loading amount of the nanoparticle was 0.51 µg/mg with an approximately 500 nm size. The Fourier transform infrared (FTIR) spectrum showed that the complexation was mainly related to the -C[bond, double bond]O, -CH, and -C-O-C- groups. The curcumin-loaded nanoparticle exhibited good stability under highly concentrated salinity stress, and the stability of the curcumin loaded in nanoparticles was significantly higher than that of free curcumin under ultraviolet radiation. The curcumin loaded in nanoparticle was released mainly in the intestinal digestion stage, and the release process was sensitive to the pH changes rather than protease. In conclusion, these nanoparticles can be a potential nanocarrier for enhancing the stability of curcumin which can be applied in the salt-containing food system.

Kidney injury molecule-1 levels are associated with therapeutic outcomes and renal tubulointerstitial injury severity in idiopathic membranous nephropathy.

Kidney injury molecule-1 (KIM-1) has an important role in chronic kidney disease development. The present study aimed to retrospectively analyze patients with idiopathic membranous nephrology (IMN) with different therapeutic outcomes to investigate the association between KIM-1 levels and therapeutic outcomes. A total of 51 patients with IMN and 20 healthy controls were included. Patients were classified into three groups: Spontaneous remission, remission with immunosuppressive therapy (IST) and nonremission with IST. Clinical and biochemical variables were collected. Urinary KIM-1 levels were measured by ELISA and renal KIM-1 expression was evaluated by immunohistochemistry. Patients with IMN were characterized as having elevated urinary and renal KIM-1 levels compared with those in the controls. Significantly increased urinary and renal KIM-1 levels were observed in the nonremission with IST group compared with those in the spontaneous remission group, and the same trend was observed for the plasma anti-podocyte antigen phospholipase A2 receptor antibody levels. Patients with more severe tubular injury (T2 index) presented with significantly higher urinary and renal KIM-1 levels than those with the T0 index. Urinary and renal KIM-1 levels were positively correlated with blood urea nitrogen, serum creatinine, serum cystatin-C, urinary albumin/creatinine ratio, urinary ß2-microglobulin and the renal interstitial fibrosis index, and they were negatively correlated with serum albumin. Furthermore, urinary KIM-1 levels were positively correlated with the renal KIM-1 levels. In conclusion, the measurement of urinary and renal KIM-1 levels may be helpful in guiding medication selection and predicting therapeutic outcomes for patients with IMN.

Extraperitoneal Laparoscopic Kidney Transplantation: Preliminary Clinical Experiences from China.

OBJECTIVE: To report on the pioneering clinical experiences of six cases of extraperitoneal laparoscopic kidney transplantation in China. METHODS: For the first time in clinical practice, a customised, controllable double-circulation cooling device was used to protect the transplanted kidney. Of the six patients, two underwent an allograft renal transplantation because they had been diagnosed with uraemia and were on maintenance haemodialysis. The other four patients underwent kidney autotransplantation because of a central renal tumour. RESULTS: The extraperitoneal laparoscopic kidney transplantations were successfully completed between 2017 and 2018. The operative time for the two patients undergoing the allograft transplantation was 3-3.5 h. The time for venous anastomosis was approximately 53-65 min, and the time for arterial anastomosis was approximately 25-30 min. The creatinine level was 90-80 µmol/L after surgery. The operative time of the four patients who underwent autotransplantation was 9.4-17.5 h. The times of venous and arterial anastomosis were 58-90 min and 35-48 min, respectively. The follow-up B-mode ultrasound after surgery showed good blood supply in the spared nephron. A renal graft was removed from one patient 6 months after surgery because of renal atrophy and dysfunction caused by poor blood supply. Five patients (two undergoing allografting and three undergoing autografting) completed the 12-month follow-up, and their renal graft function was good. CONCLUSIONS: Extraperitoneal laparoscopic kidney transplantation, either allograft or autologous transplantation, is a safe and feasible procedure with a good chance of survival for the transplanted kidney. A customised cooling device is effective and practical during laparoscopic kidney transplantation.

The diagnostic performance of CESM and CE-MRI in evaluating the pathological response to neoadjuvant therapy in breast cancer: a systematic review and meta-analysis.

OBJECTIVES: Neoadjuvant chemotherapy (NAC) is an important method for breast cancer treatment. By monitoring its pathological response, the selection of clinical treatment strategies can be guided. In this study, the meta-analysis was used to compare the accuracy of contrast-enhanced MRI (CE-MRI) and contrast-enhanced spectral mammography (CESM) in detecting the pathological response of NAC. METHODS: Literatures associated to CE-MRI and CESM in the evaluation of pathological response of NAC were searched from PubMed, Cochrane Library, web of science, and EMBASE databases. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the quality of studies. Pooled sensitivity, specificity, and the area under the SROC curve were calculated to evaluate the diagnostic accuracy of CE-MRI and CESM in monitoring the pathological response of NAC. RESULTS: There were 24 studies involved, 18 of which only underwent CE-MRI examination, three of which only underwent CESM examination, and three of which underwent both CE-MRI and CESM examination. The pooled sensitivity and specificity of CE-MRI were 0.77 (95%CI, 0.67-0.84) and 0.82 (95%CI, 0.73-0.89), respectively. The pooled sensitivity and specificity of CESM were 0.83 (95%CI, 0.66-0.93) and 0.82 (95%CI, 0.68-0.91), respectively. The AUCs of SROC curve for CE-MRI and CESM were 0.86 and 0.89, respectively. CONCLUSIONS: Compared to CE-MRI, CESM has equal specificity, greater sensitivity and excellent performance, which may have a brighter prospect in evaluating the pathological response of breast cancer to NAC. ADVANCES IN KNOWLEDGE: CESM showed equal specificity, greater sensitivity, and excellent performance than CE-MRI.

Epigallocatechin­3­gallate protects from high glucose induced podocyte apoptosis via suppressing endoplasmic reticulum stress.

Podocytes serve a critical role in the development of many glomerular diseases, including diabetic nephropathy (DN). Epigallocatechin­3­gallate (EGCG), a predominant polyphenolic component of green tea, has indicated its therapeutic effects in diabetes. In the present study, mouse podocyte cells were cultured in vitro, cell injury was induced by high glucose, and the protective effect of EGCG on cell proliferation and apoptosis and the underlying mechanisms were investigated. The results demonstrated that high glucose significantly inhibited cell proliferation after 48 and 72 h compared with normal glucose and mannitol treatment. EGCG (20 µmol/l) markedly promoted podocyte proliferation after 24, 48 and 72 h incubation with high glucose. Furthermore, high glucose significantly reduced WT­1 and nephrin expression in podocytes compared with the normal glucose and mannitol groups, while EGCG (20 µmol/l) treatment largely restored their expression. High glucose also significantly increased the apoptotic cell population compared with normal glucose and mannitol groups. However, EGCG combined with high glucose greatly decreased the apoptotic cell number compared with high glucose treatment alone. Furthermore, high glucose treatment was demonstrated to significantly increase glucose­regulated protein 78 (GRP78), phosphorylated­ PKR­like ER kinase (p­PERK) and caspase­12 protein expression levels, which is representative of endoplasmic reticulum (ER) stress, compared with the normal glucose and mannitol groups. However, EGCG treatment significantly attenuated GRP78, p­PERK and caspase­12 protein expression induced by high glucose. These findings suggested that EGCG serves a protective role in glucose­induced podocyte apoptosis via suppressing ER stress, and may provide a novel therapeutic strategy to ameliorate the process of DN.