Pathological response to neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma in Eastern versus Western countries: meta-analysis.

OBJECTIVE: Locally advanced oesophageal squamous cell carcinoma can be treated with neoadjuvant chemoradiotherapy or chemotherapy followed by oesophagectomy. Discrepancies in pathological response rates have been reported between studies from Eastern versus Western countries. The aim of this study was to compare the pathological response to neoadjuvant chemoradiotherapy in Eastern versus Western countries. METHODS: Databases were searched until November 2022 for studies reporting pCR rates after neoadjuvant chemoradiotherapy for oesophageal squamous cell carcinoma. Multi-level meta-analyses were performed to pool pCR rates separately for cohorts from studies performed in centres in the Sinosphere (East) or in Europe and the Anglosphere (West). RESULTS: For neoadjuvant chemoradiotherapy, 51 Eastern cohorts (5636 patients) and 20 Western cohorts (3039 patients) were included. Studies from Eastern countries included more men, younger patients, more proximal tumours, and more cT4 and cN+ disease. Patients in the West were more often treated with high-dose radiotherapy, whereas patients in the East were more often treated with a platinum + fluoropyrimidine regimen. The pooled pCR rate after neoadjuvant chemoradiotherapy was 31.7% (95% c.i. 29.5% to 34.1%) in Eastern cohorts versus 40.4% (95% c.i. 35.0% to 45.9%) in Western cohorts (fixed-effect P = 0.003). For cohorts with similar cTNM stages, pooled pCR rates for the East and the West were 32.5% and 41.9% respectively (fixed-effect P = 0.003). CONCLUSION: The pathological response to neoadjuvant chemoradiotherapy is less favourable in patients treated in Eastern countries compared with Western countries. Despite efforts to investigate accounting factors, the discrepancy in pCR rate cannot be entirely explained by differences in patient, tumour, or treatment characteristics.

Comparison of laparoscopic, robotic, and open retroperitoneal lymph node dissection for non-seminomatous germ cell tumor: a single-center retrospective cohort study.

PURPOSE: To compare the perioperative outcomes of L-RPLND, R-RPLND and O-RPLND, and determine which one can be the mainstream option. METHODS: We retrospectively reviewed medical records of 47 patients undergoing primary RPLND by three different surgical techniques for stage I-II NSGCT between July 2011 and April 2022 at our center. Standard open and laparoscopic RPLND was performed with usual equipment, and robotic RPLND was operated with da Vinci Si system. RESULTS: Forty-seven patients underwent RPLND during 2011-2022, and 26 (55.3%) of them received L-RPLND, 14 (29.8%) were operated with robot, while 7 (14.9%) were performed O-RPLND. The median follow-up was 48.0 months, 48.0 months, and 60.0 months, respectively. The oncological outcomes were comparable among all groups. In L-RPLND group, there were 8 (30.8%) cases of low grade (Clavien I-II) complications, and 3 (11.5%) cases of high-grade (Clavien III-IV) complications. In R-RPLND group, one (7.1%) low-grade complication and four (28.6%) high-grade complications were observed. In O-RPLND group, there were 2 (28.5%) cases of low-grade complications and one case (14.2%) of high-grade one. The operation duration of L-RPLND was the shortest. In O-RPLND group, the number of positive lymph nodes were higher than other two groups. Patients undergoing open surgery had lower (p < 0.05) red blood cell count, hemoglobin level, and higher (p < 0.05) estimated blood loss, white blood cell count than those receiving either laparoscopic or robotic surgery. CONCLUSION: All three surgical techniques are comparable in safety, oncological, andrological, and reproductive outcomes under the circumstance of not using primary chemotherapy. L-RPLND might be the most cost-effective option.

Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer.

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.

Palladium/Brønsted-Acid-Catalyzed Diastereoselective Cyclization with Chiral Sulfinamides as Nucleophiles.

This article reports diastereoselective cyclization with chiral sulfinamides as nucleophiles in two reaction pathways: (1) intramolecular allylic substitution and (2) sequential aerobic oxidation with aza-Michael addition. These reactions were enabled by synergistic palladium and Brønsted acid catalysis and produced chiral isoindolines with good yields of 55-92% and high diastereoselectivities of 10:1 to >20:1 dr.

A positive feedback loop between TAZ and miR-942-3p modulates proliferation, angiogenesis, epithelial-mesenchymal transition process, glycometabolism and ROS homeostasis in human bladder cancer.

BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. METHODS: qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. RESULTS: We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. CONCLUSION: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.

Virulence and Molecular Diversity in the Kabatiella zeae Population Causing Maize Eyespot in China.

Maize eyespot, caused by Kabatiella zeae, has become a major yield-limiting factor in maize planting areas in northeast China. Limited information is available on pathotypes, virulence, and the genetic diversity of the K. zeae population. We analyzed virulence and genetic diversity of 103 K. zeae isolates collected from six provinces in China with differential hosts and the amplified fragment length polymorphism (AFLP) technique, respectively. To evaluate the virulence, 103 isolates were inoculated on nine differential hosts (maize inbred lines)-E28, Shen137, Qi319, B73, Danhuang34, Zi330, Mo17, Huangzaosi, and CN165-and grouped into 23 pathotypes and three virulence groups according to the coded triplet nomenclature system on differential hosts. AFLP analysis resolved the set of isolates into four genetic diversity clusters (DICE similarity values of 76%). Genetic variation of K. zeae among and between pathotypes revealed that the pathogen population had a high genotypic diversity. The correlation between pathotypes, virulence, and genetic diversity grouping was low. A correlation between AFLP groups and geographic locations was detected.

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression.

Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.

Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 axis in human bladder cancer cells.

Artesunate is a kind of derivative of artemisinin, which possesses potent anti-cancer effect in addition to its anti-malarial property. And autophagy was a highly conserved process, exerting a double-edged effect in cancer cell survival. Besides, apoptosis is a programmed cell death program, crucial to cell homeostasis. However, the relations between autophagy and apoptosis, and the role of artesunate in this interaction have not been elucidated in bladder cancer. In present study, we used human bladder cancer cells (T24 and EJ cell lines) to investigate that how artesunate would influence autophagy and apoptosis processes. We found that artesunate could inhibit the viability, proliferation and migration of bladder cancer cells, as well as induce autophagy in a time and dose dependent manner, in addition, the artesunate induced autophagy subsequently activated cells apoptosis. Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis. In the upstream, ROS upregulation triggered by ART initiated AMPK-mTOR-ULK1 axis. However, this initiative effect of ROS can be reversed by N-Acetyl-l-cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells.

Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells.

Bladder cancer is one of the most frequently occurring malignant tumors in the urinary system. Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells. MicroRNAs (miRNAs) and autophagy play crucial roles in cancer occurrence and development. In the present study, we evaluated the anticancer effects, including cell migration inhibition and the apoptotic effects of NaB in human bladder cancer cells. Furthermore, we found that NaB inhibited migration and induced AMPK/mTOR pathway-activated autophagy and reactive oxygen species (ROS) overproduction via the miR-139-5p/Bmi-1 axis. In addition, we found that ROS overproduction contributed to NaB-induced caspase-dependent apoptosis and autophagy. The interplay between autophagy and apoptosis in NaB treatment was clarified. Our findings provide a further understanding of EMT reversion, apoptosis and autophagy induced by antitumor drugs and a novel perspective and alternative strategy for bladder cancer chemotherapy.

Hydration and Chronic Kidney Disease Progression: A Critical Review of the Evidence.

We performed a comprehensive literature review to examine evidence on the effects of hydration on the kidney. By reducing vasopressin secretion, increasing water intake may have a beneficial effect on renal function in patients with all forms of chronic kidney disease (CKD) and in those at risk of CKD. This potential benefit may be greater when the kidney is still able to concentrate urine (high fluid intake is contraindicated in dialysis-dependent patients). Increasing water intake is a well-accepted method for preventing renal calculi, and current evidence suggests that recurrent dehydration and heat stress from extreme occupational conditions is the most probable cause of an ongoing CKD epidemic in Mesoamerica. In polycystic kidney disease (PKD), increased water intake has been shown to slow renal cyst growth in animals via direct vasopressin suppression, and pharmacologic blockade of renal vasopressin-V2 receptors has been shown to slow cyst growth in patients. However, larger clinical trials are needed to determine if supplemental water can safely slow the loss of kidney function in PKD patients.

Effect of increased water intake on plasma copeptin in patients with chronic kidney disease: results from a pilot randomised controlled trial.

OBJECTIVES: Increased water intake may have a beneficial effect on the kidney through suppression of plasma vasopressin. We examined the effect of increased water intake on plasma copeptin (a marker of vasopressin) over 6 weeks in patients with chronic kidney disease. DESIGN: Secondary analysis of a randomised controlled parallel-group pilot trial. SETTING: Canada, 2012-2013. PARTICIPANTS: 28 patients with stage 3 chronic kidney disease randomised (2:1) to a hydration (n=17) or control group (n=11). INTERVENTION: The hydration group was coached to increase water intake by up to 1.5 L/day for 6 weeks. The control group was asked to maintain regular water intake. MEASURES AND OUTCOMES: Participants provided blood and 24 h urine samples at baseline and 6 weeks. Change in plasma copeptin was compared within and between study groups. RESULTS: Participants were 64% male with a mean age of 62 years and an estimated glomerular filtration rate of 40 mL/min/1.73 m(2). Between baseline and 6 weeks, 24 h urine volume increased by 0.7 L/day in the hydration group, rising from 2.3 to 3.0 L/day (p=0.01), while decreasing by 0.3 L/day among controls, from 2.0 to 1.7 L/day (p=0.07); between-group difference: 0.9 L/day (95% CI 0.37 to 1.46; p=0.002). In the hydration group, median copeptin decreased by 3.6 pmol/L, from 15.0 to 10.8 pmol/L (p=0.005), while remaining stable among controls at 19 pmol/L (p=0.76; p=0.19 for the between-group difference in median change); the between-group difference in mean change was 5.4 pmol/L (95% CI -1.2 to 12.0; p=0.11). CONCLUSIONS: Adults with stage 3 chronic kidney disease can be successfully randomised to drink approximately 1 L more per day than controls. This increased water intake caused a significant decrease in plasma copeptin concentration. Our larger 12-month trial will examine whether increased water intake can slow renal decline in patients with chronic kidney disease. TRIAL REGISTRATION NUMBER: NCT01753466.

Biosensing using microring resonator interferograms.

Optical low-coherence interferometry (OLCI) takes advantage of the variation in refractive index in silicon-wire microring resonator (MRR) effective lengths to perform glucose biosensing using MRR interferograms. The MRR quality factor (Q), proportional to the effective length, could be improved using the silicon-wire propagation loss and coupling ratio from the MRR coupler. Our study showed that multimode interference (MMI) performed well in broad band response, but the splitting ratio drifted to 75/25 due to the stress issue. The glucose sensing sensitivity demonstrated 0.00279 meter per refractive-index-unit (RIU) with a Q factor of ~30,000 under transverse electric polarization. The 1,310 nm DFB laser was built in the OLCI system as the optical ruler achieving 655 nm characterization accuracy. The lowest sensing limitation was therefore 2 × 10-4 RIU. Moreover, the MRR effective length from the glucose sensitivity could be utilized to experimentally demonstrate the silicon wire effective refractive index with a width of 0.45 mm and height of 0.26 mm.

Nocturnal home hemodialysis associates with improvement of electrocardiographic features linked to sudden cardiac death.

Sudden cardiac death (SCD) remains the leading cause of death in hemodialysis patients. We performed a retrospective electrocardiograph (ECG) and chart review to determine whether hemodialysis modality, frequency, or duration could predict change in ECG parameters associated with SCD. Frequent nocturnal hemodialysis was associated with an improvement in Tpeak to Tend within 365 days (83.8-71.8 ms, p = 0.005) and past 365 days of dialysis initiation (85.9-77.1 ms, p = 0.005) and improvement in QRS amplitude variation within 365 days (0.0583-0.0297, p = 0.025) and past 365 days of dialysis initiation (0.0546-0.0332, p = 0.029). Compared with intermittent conventional hemodialysis, more frequent nocturnal (15/25 vs. 3/14, p = 0.04) and intermittent nocturnal hemodialysis (INHD) (6/8 vs. 3/14, p = 0.03) patients decreased Tpeak to Tend. More short-hours daily than INHD patients increased T-wave amplitude variation (16/25 vs. 1/8, p = 0.02). These improvements occurred before changes in Cornell or Sokolow-Lyon electrocardiographic left ventricular mass. Thus, it appears that hemodialysis modalities of longer duration are associated with improvements in electrocardiographic parameters associated with SCD. Prospective trials are required to determine whether dialysis prescription reduces SCD, cardiovascular morbidity, and mortality in hemodialysis patients.

Modifiable variables affecting interdialytic weight gain include dialysis time, frequency, and dialysate sodium.

Interdialytic weight gain (IDWG) is associated with hypertension, left ventricular hypertrophy, and all-cause mortality. Dialysate sodium concentration may cause diffusion gradients with plasma sodium and influence subsequent IDWG. Dialysis time and frequency may also influence the outcomes of this Na(+) gradient; these have been overlooked. Our objective was to identify modifiable factors influencing IDWG. We performed a retrospective multivariable regression analyses of data from 86 home hemodialysis patients treated by hemodialysis modalities differing in frequency and session duration to determine factors involved that predict IDWG. Age, diabetic status, and residual renal function did not correlate with IDWG in the univariable analysis. However, using a combination of backwards selection and Akaike information criterion to build our model, we created an equation that predicted IDWG on the basis of serum albumin, age, patient sex, dialysis frequency, and the diffusive balance of sodium, represented by the product of the duration of dialysis and the patient plasma to dialysate Na(+) gradient. This equation was internally validated using bootstrapping, and externally validated in a temporally distinct patient population. We have created an equation to predict IDWG on the basis of independent factors readily available before a dialysis session. The modifiable factors include dialysis time and frequency, and dialysate sodium. Patient sex, age, and serum albumin are also correlated with IDWG. Further work is required to establish how improvements in IDWG influence cardiovascular and other clinical outcomes.