Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Pelvic floor ultrasound versus urodynamics in evaluating insensible urinary incontinence: A retrospective study.

OBJECTIVE: Insensible Urinary Incontinence (IUI) is a situation when you complain of urinary incontinence but are unaware of how it occurred. Therefore, it is necessary to apply highly specific diagnostic methods to promote accuracy in the diagnosis of IUI, including pelvic floor ultrasound (PFU) and urodynamic studies (UDS). METHODS: A total of 41 women with IUI were retrospectively included. Patients were categorized into two groups: the urodynamic urinary incontinence group (UUI group, n=20) and the non-urodynamic urinary incontinence group (NUUI group, n=21), according to the urine leakage during UDS. The baseline clinical characteristics, UDS results, and PFU parameters were collected. RESULTS: Compared with the NUUI group, the UUI group had a smaller maximum cystometric capacity (P=0.008), lower maximum urethral closure pressure (P=0.005), shorter functional urethral length (FUL) (P=0.01), more bladder neck funneling (BNF) (P=0.02), greater BNF depth (P=0.04), and larger BNF area (P=0.01). The area and depth of BNF were negatively correlated with maximum urethral closure pressure (r=-0.42, P=0.01), FUL (r=-0.36, P=0.02 versus r=-0.39, P=0.01), and maximum cystometric capacity (r=-0.35, P=0.03), but positively correlated with maximum urinary flow rate (r=0.33, P=0.04 versus r=0.36, P=0.02). The canonical correlation analysis of the ultrasound parameters and UDS parameters shows that the first pair of canonical variables was statistically significant (r1=0.9, P<0.001). CONCLUSIONS: The PFU is associated with UDS in evaluating IUI. It has the advantages of low cost and high comfort, thus should be used as an auxiliary examination for IUI.

[Aldo-keto reductase family 1 B10 participates in the regulation of hepatoma cell cycle through p27/p-Rb signaling pathway].

Objective: Aldo-keto reductase family 1 member B10 (AKR1B10) pathogenesis, early diagnosis and prognosis are closely related with hepatoma. Therefore, this study explores the effect and mechanism of AKR1B10 on cell cycle in hepatoma cells. Methods: HepG2 cells were infected with lentivirus LV-AKR1B10-shRNA or treated with epalrestat, an AKR1B10 inhibitor. The expression level of AKR1B10 was detected by Western blot assay and real-time fluorescence quantitative PCR (RT-qPCR). Decreased AKR1B10 activity was detected by reduced coenzyme II (NADPH) absorbance at 340 nm. The low expression of AKR1B10 and the effect of different concentrations of epalrestat on cell proliferation and cell cycle were detected by CCK-8 method and flow cytometry. The protein expression levels of p-rb, cyclin D1, E1, p27 in HepG2 cells were detected by Western blot. The mean of the two samples was tested using independent sample t-test. Results: AKR1B10 expression level in hepatoma cells was significantly increased compared to normal liver cells, and the relative expression level of AKR1B10 protein in HepG2 cells was 6.71 ± 1.11 (P = 0.012). Epalrestat was significantly inhibited with the enzymatic activity of AKR1B10 in a dose-dependent manner. AKR1B10 gene in HepG2 cells was effectively silenced. HepG2 cells treated with different concentrations of epalrestat (AKR1B10 inhibitor) for 24, 48 and 72 h had inhibited cell proliferation, promoted G0/G1 cell cycle arrest, reduced the expression of p-Rb, cyclin D1, and cyclin E1 and increased the expression of cyclin dependent kinase inhibitor p27 expression. Conclusion: AKR1B10 inhibitory expression and activity can promote G0/G1 cell cycle arrest in HepG2 cells through the p27 / p-Rb pathway.

MicroRNAs in gastric cancer: from bench to bedside.

Gastric carcinogenesis results from complex interactions between host and environmental and bacterial factors, and this leads to genetic and epigenetic deregulation of oncogenic and tumor-suppressive genes. MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate almost 30% of human genes post transcriptionally and they are crucial in the initiation and progression of various diseases; especially malignancies. Accumulated evidence documents changes in gene sequences and epigenetic modifications. These then lead to abnormal miRNA expression in gastric cancer (GC) and also to deregulated miRNAs which act as oncogenes or tumor suppressors by regulating related target genes and contributing to malignant phenotypes. This altered miRNA expression in body fluids could well provide a novel biomarker for GC patient diagnosis and prognosis. MiRNAs present a promising target for GC treatment, and more tempting, for eradication of gastric cancer stem cells. This latter sub-group of tumor cells is thought to initiate and maintain GC development. Herein, we review the aberrant expression of miRNA expression and the underlying mechanisms and consequential effects of miRNA de-regulation. This identifies the responsible gastric cancer target genes, and highlights potential clinical applications.

Treating ureteric obstruction secondary to gynecological disease assisted with retrograde ureteroscopic stenting.

OBJECTIVE: To analyze the technical experience and clinical efficacy of ureteroscopic treatment of middle and lower ureteral obstruction due to gynecological disease. PATIENTS AND METHODS: From January 2007 to December 2015, 58 cases of ureteral obstruction were collected in 55 patients caused by gynecological factors. 19 cases had the history of gynecological iatrogenic injury and 39 cases were secondary to gynecological tumors. Different situations of luminal stenosis included obliteration, suture penetration, transection and unrecognized ureteral orifice. The ureteral stents were retrogradely placed ureteroscopically assisted by holmium laser or transurethral plasma kinetic resection. RESULTS: A total of 51 cases of operations were completed successfully by one-stage ureteroscopic stenting with the mean operation time of 33.5 min. No severe complications were observed. The serum creatinine two weeks after operation had a significant decline compared with that of preoperation (p<0.05). The mean follow-up time was 5.3 months. 44 cases with successful stent placement showed nice improvement of hydronephrosis by ultrasound. CONCLUSIONS: Ureteroscopic stent placement with the use of holmium laser or plasma kinetic resection device, has good clinical effects, which provides a relatively simple and minimal-invasive treatment option to resolve middle and lower ureteral obstruction caused by complex gynecological factors.

Effect of the Schneiderian membrane on the formation of bone after lifting the floor of the maxillary sinus: an experimental study in dogs.

A titanium membrane was used to isolate the Schneiderian membrane of the bony walls of the sinus so that we could investigate their role on the formation of bone after sinus lifts compared with a control group (conventional raising of the sinus floor) in which we did not use a membrane to isolate any area. Three canine models of lifting the sinus floor using the lateral window technique were established: conventional lifting of the floor (control group), raising of the floor with the mucosa shielded (mucosal shielding group), and raising of the floor with the bony wall shielded (bony wall shielding group). The formation of bone one and three months after the sinus floor had been lifted was compared in each group both grossly and by histopathological examination. An appreciable amount of new bone had formed in the control group, with abundant areas near the inferior bony wall, and some near the raised Schneiderian membrane. Similarly, new bone had also formed in the mucosal shielding group, with abundant new bone near the inferior bony wall, but none near the raised Schneiderian membrane. However, there was considerably less new bone in the bony wall shielding group, with none in tissues adjacent to the inferior bony wall and little in tissues near the raised Schneiderian membrane. The Schneiderian membrane has osteogenic capability and participates in the formation of bone after the sinus floor has been lifted. However, its osteogenic role is weaker than that of the surrounding bony wall of the maxillary sinus.

Aortic compliance in human hypertension.

Aortic compliance in normotensive and hypertensive Chinese subjects undergoing diagnostic cardiac catheterization was compared by using a newly described method that allows for determination of the pressure dependence of compliance if one assumes a value for the exponential coefficient of the pressure-volume relation of the large arteries. Under baseline conditions in the normotensive and hypertensive groups at mean aortic pressures of 96.3 and 128.6 mm Hg, aortic compliance averaged 1.47 and 0.80 ml/mm Hg, respectively. Compliance in the hypertensive group at a diastolic pressure of 99.4 mm Hg (which was nearly equal to the mean normotensive pressure) was 1.072 ml/mm Hg--still significantly lower than in the normotensive group. During nitroprusside infusion, however, the compliances in the hypertensive group increased to levels equal to or greater those in the normotensive group. Thus, these data confirm that aortic compliance is lower in hypertensive than in normotensive humans. They further demonstrate that the lower compliance cannot be attributed entirely to the elevated blood pressure, suggesting that excess smooth muscle tone may be partly responsible.

Iliac periosteal graft with vascular pedicle in the treatment of avascular necrosis of the femoral head. Experimental study and clinical application.

From March 1983 to June 1987, 6 patients with avascular necrosis of the femoral head were treated with vascular pedicled iliac periosteum graft. Follow-up for 3 to 7.5 years showed satisfactory results. The patients experienced no hip pain, could walk freely, and resumed work after the treatment. X-ray films showed that the original defect of the femoral head was filled up and its outline was clear and smooth. The bone density of the femoral head and neck normalized. The experimental study indicated that the vascularized periosteum improves the blood supply and initiates the revascularization and osteogenesis of the femoral head. The authors conclude that the technique is suitable for the treatment of avascular necrosis of the femoral head of Stage II and III.

Transposition of iliac periosteum with vascular pedicle and compression screw fixation for transcervical fracture of femur. Experimental research and clinical application.

The vascular pedicled periosteum was used in 11 cases in our hospital for the treatment of femoral neck fracture with good result. The follow-up period ranged from 2 to 6 years, with an average of 4 years. Animal experiment was made to elucidate the repairing process. It demonstrated that the pedicled periosteum played double roles, namely, blood supply and osteogenesis. The clinical and experimental results are presented.

[Treatment of traumatic shortening of the legs in adults].

Non-traumatic shortening of lower extremities can be lengthened by osteotomy, traction or bone grafting. In traumatic shortening, treatment is limited by several reasons and emphasis should be put on bone healing and preserving of loading and walking functions. The lengthening of lower extremities has some difficulties. Recently, we have adopted a method in which we transposed muscle-skin flap to repair the stick-bone scar in the early stage, and performed traction with Hoffman extra-frame (when osteotomy is needed) in the mid-stage and bone grafting (with or without vascularity) in the late stage. From April 1984 to April 1986, seven patients were treated by this method. The result was satisfactory. In this article is discussed the pathologic characteristics of traumatic shortening of the lower extremities and the role of the gastrocnemius in repairing skin defect.

[Quantitative study on the osteogenic potential of vascularized iliac periosteal].

The effect of pedical blood supply, recipient environment, blood supply to the osteogenic capacity of iliac periosteal was investigated. An iliac periosteal flap based on the circumflexa femoris lateralis vessels was developed in a canine model. The vascularied iliac periosteal was rotated onto the quadriceps femoris musculus or epigastrica inferior fibrous-connective tissues in one side and the free flap was done in the same way in another side. 2, 2, 4, 6 animals were killed at 2, 4, 8, 12 week after operation and the flaps were studied by new bone Ca, P content, bone dense measure, double tetracycline labeling, bone histomorphometry analysis and light microscopy. The following results were obtained: (1) Iliac periosteal has good osteogenic capacity; (2) The early good blood supply is much more important than the recipient environment blood supply, it make the bone formation speed 2-4 weeks forward.

[Induction of gastric adenocarcinoma in Wistar rats following neonatal exposure to MNNG and neoplastic transformation assay of DNA of the induced cancer].

Adenocarcinoma, adenoma and dysplasia of the stomach of adult Wistar rats were induced following administration of MNNG for 10 days by gavage when they were new-born. The incidence of the three types of pathological lesions at the dose of 0.4 mg MNNG per rat being 39%, 50% and 100% respectively. Induction of gastric adenocarcinoma is dose-dependent. The incidence of adenocarcinoma in male rats being significantly higher then that of female rats (P < 0.02). 23 of 33 (70%) induced cancers were found in the gastric antrum. By the use of DNA cotransfection technique and the assay of carcinogenicity in the Balb/c nude mice, it was also found that the DNA of 4 of the 6 induced gastric carcinomas could transform NIH/3T3 cells into malignant cells, an indication that the induced cancer DNA contains transforming gene.