Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

Objective To discuss the medium-term follow-up of clinically insignificant residual fragments (CIRF) after minimally invasive percutaneous nephrolithotomy lithotripsy (MPCNL).Methods The clinical data of 72 patients with CIRF medium-term follow-up were analyzed retrospectively.Results Seventy-two patients with CIRF.The anatomical distribution of CIRF was 10 at upper pole,15 at middle,35 at lower,10 at renal ureteropelvie junction and 2 at upper and lower pole.Stone analysis showed that 41 cases of calcium oxalate calculi,16 of calcium oxalate calculi mixed with carbonate calculi,3 calcium oxalate calculi mixed with uric acid,4 calcium oxalate calculi mixed with struvite stone,3 struvite stone,2 uric acid stone and 3 carbonate apatite mixed with struvite stone.Fifteen cases had clinical symptoms,including 2 renal colic pain,8 hematuria,5 lower urinary tract symptoms,4 cases CIRF located in upper pole,1 case in middle pole,4 cases in lower pole,6 cases in ureteropelvic junction,the incidence of clinical symptoms in ureteropelvic junction was significantly higher than that in other locations (6/10 vs.4/12,1/15,4/37,P ＜0.05).Eight cases required surgical procedure,5 cases underwent extracorporeal shock wave lithotripsy,3 cases with ureteral CIRF were performed with ureteroscopic lithotripsy.CIRF were clear after surgery,7 patients with ureteral CIRF had renal colic pains.The stones were excluded after spasmolytic analgesic treatments.Conclusions CIRF can be located variously in the kidney and ureter.Most CIRF are calcium oxalate calculi and locate in the lower pole.Patients with the history of previous open surgery or extracorporeal shock wave lithotripsy are more likely to get CIRF.Medium-term follow-up of CIRF reveals that CIRF located in the renal ureteropelvis junction are more likely to have clinical symptoms.

Objective To evaluate the clinical effects and safety of percutaneous nephrolithotomy (PCNL) by middle renal calice used as the main target for the treatment of staghorn stones with the combination of pneumatic and ultrasonic lithotrite.Methods Clinical data of 73 patients underwent PCNL by middle renal calices as main access with 57 incomplete staghorn stones and 35 complete staghorn stones.To observe the situation calculus removal rate and complications.Results Seventy cases (88 sides) underwent one session PCNL by single access tract (middle caliees),3 cases (4 sides) underwent one session PCNL by double access tracts (2 cases by middle and low calices,1 case by up and middle caliees).After the first period of lithoclasty,17 patients (25 sides) residual stones and the stone removal rate 72.8％ (67/92),among these patients,1 case (1 side) had fragments of lateral renal calyeeal stones with no further treatment.Other 16 cases (24 sides)underwent second session PCNL,all were treated by single access tract (middle calices) and 2 cases (2 sides)had extracorporeal shock wave lithotripsy before the second PCNL.After the second period of lithoclasty,76 sides composed of 27 complete staghorn stones and 49 incomplete staghorn stones had no residual fragments with the stone removal rate 82.6％ (76/92).The operative time lasted 120-320 min.Hemoglobin dropped 1-4 g/L,11 cases in the operation procedure and 3 cases after operation needed blood transfusion respectively.One case of renal pelvic infection after operation and 1 case had split renal dysfunction with peri-parenchyma infection.The hospitalization time was 9-18 days.Conclusion It is effective and safe to perform PCNL for staghorn stone by middle calices as a main access.Combining pneumatic and ultrasonic lithotrite will be very useful with high stone clearance,short procedure time and less complications.

This study examined the effect of silencing LRIG3 expression on the proliferation and apoptosis of bladder cancer T24 cells and explored the role of LRIG3 in the tumorigenesis of bladder cancer.Bladder cancer T24 cells were routinely cultured and pSilencer plasmids were employed to construct LRIG3 eukaryotic expression vector of LRIG3-siRNA,i.e.,pSilencer-LRIG3-siRNA.After confirmation,the vector was transfected into HEK293 cells to make a replication-deficient adenovirus,pAd-LRIG3-siRNA,which was then introduced into bladder cancer T24 cells.RT-PCR,Western-blotting were performed to detect the levels of LRIG3 mRNA and proteins.Cells number was determined by using MTT test.Hoechst33258 staining,transmission microscopy,flow cytometery were conducted to examine the cell apoptosis.Three groups included a blank control group,a negative control group (containing non-interfering plasmids) and a pAd-LRIG3-siRNA group.Our results showed that the recombinant pAd-LRIG3-siRNA was successfully transfected into the bladder cancer T24 cells.The siRNA formed by the transcription of the recombinant plasmids resulted in significantly reduced expressions of LRIG3 gene and protein and significantly decreased cell proliferation and growth in the pAd-LRIG3-siRNA group as compared with the control group (P＜0.01).The siRNA also caused apoptotic changes of some cells,with the apoptosis rate being (17.69±0.75)％,which was significantly different from that of the control group (P＜0.01).It was concluded that recombinant pAd-LRIG3-siRNA plasmids could effectively decrease the expression of LRIG3 mRNA and proteins and,to some extent,inhibit the proliferation and promote the apoptosis of bladder cancer T24 cells.Silencing LRIG3 gene might be a novel alternative for the treatment of bladder cancer.

This study examined the effect of silencing LRIG3 expression on the proliferation and apoptosis of bladder cancer T24 cells and explored the role of LRIG3 in the tumorigenesis of bladder cancer. Bladder cancer T24 cells were routinely cultured and pSilencer plasmids were employed to construct LRIG3 eukaryotic expression vector of LRIG3-siRNA, i.e., pSilencer-LRIG3-siRNA. After confirmation, the vector was transfected into HEK293 cells to make a replication-deficient adenovirus, pAd-LRIG3-siRNA, which was then introduced into bladder cancer T24 cells. RT-PCR, Western-blotting were performed to detect the levels of LRIG3 mRNA and proteins. Cells number was determined by using MTT test. Hoechst33258 staining, transmission microscopy, flow cytometery were conducted to examine the cell apoptosis. Three groups included a blank control group, a negative control group (containing non-interfering plasmids) and a pAd-LRIG3-siRNA group. Our results showed that the recombinant pAd-LRIG3-siRNA was successfully transfected into the bladder cancer T24 cells. The siRNA formed by the transcription of the recombinant plasmids resulted in significantly reduced expressions of LRIG3 gene and protein and significantly decreased cell proliferation and growth in the pAd-LRIG3-siRNA group as compared with the control group (P<0.01). The siRNA also caused apoptotic changes of some cells, with the apoptosis rate being (17.69±0.75)%, which was significantly different from that of the control group (P<0.01). It was concluded that recombinant pAd-LRIG3-siRNA plasmids could effectively decrease the expression of LRIG3 mRNA and proteins and, to some extent, inhibit the proliferation and promote the apoptosis of bladder cancer T24 cells. Silencing LRIG3 gene might be a novel alternative for the treatment of bladder cancer.

Objective To compare the outcomes of antegrade and retrograde approach ureteroscopy for impacted upper ureteric calculi and assess the safety and efficiency of the two types of minimally invasive technique. Methods A total of 106 patients with impacted upper ureteric calculi were treated with ureteroscopy. The procedure was performed via antegrade percutaneous nephrostomy tract in 50 patients (antegrade group) and via retrograde transurethral access in 56 patients (retrograde group). Results The success rate of retrograde group was 92.9% (52/56). Operating time was (45 ± 5 ) min, hospital stay was (6 ± 1) days. The stone free rate was 80.4%(45/56) at 1 month follow-up,7 patients with residual calculi required ESWL combination. Complication rate was 5.4% (3/56). The success rate of antegrade group was 100.0% (50/50). Operating time was (55 ± 8 ) min, hospital stay was (8 ± 2) days. The stone free rate was 100.0% (50/50) and no complication was noted. The stone free rate and the complication rate indicated significant difference between the two groups (P ＜ 0.05). Conclusions Antegrade and retrograde access ureteroscopy for impacted upper ureteric calculi are safe and effective. Success rate and stone free rate of antegrade approach are higher than those of retrograde approach.

Objective To investigate the therapeutics of solitary kidney complicated with complexcalculi,and improve the effect and safety of treatment.Methods Experiences in the treatment of 32 patients with solitary kidney complicated with complex calculi were summarized.Congenital solitary kidney was 6 cases (18.8%),postnatal reason was 26 cases(81.2%),left was 12 cases(37.5%),right was 20 cases (62.5%).All patients were with mould or multiple calculi,9 cases were complicated with ureter calculi,and 8 cases were hospitalized because of obstructive anuria.The patients with mould calculi received extracorporeal shock-wave lithotripsy (ESWL) prior to percutaneous nephrolithotomy(PCNL).While the patients with multiple calculi received PCNL prior to ESWL. Some cases were treated by lithedialysis.Results Twenty-nine cases (90.6%)were cured by ESWL combined with PCNL 12 cases received lithodialysis during PCNL. Eight cases with obstructive anuria recovered in 12 hours after emergent ESWL or lithodialysis,3 cases(9.4%)underwent open operation because of deformity or obstruction in renal pelvis and ureter,1 case had to keep nephrostomy because of repeated infection.Followed up 4-36 months,29 cases (90.6%)kept good kidney function,3 cases(9.4%)had renal insufficiency,2 cases(6.2%)reoccurred calculi.Conclusions The therapeutics of ESWL combined with PCNL may clear complex calculi of solitary kidney effectively and safely.It is necessary to take emergent ESWL in renal obstructive calculi cases.And the patients with lower ureter obstructive calculi may take lithodialysis first.It is proper to choose open operation on the patients with deformity of renal pelvis or obstruction of ureter.

Objective To study the role of interleukin-6(IL-6)in the pathogenesis of prostate cancer and its clinical significance. Methods Immunohistochemistry and RT-PCR were used to detect the expression of IL-6 protein and mRNA in frozen prostatic adenocarcinoma,adjacent benign prostatic tissue,and prostate cancer cell lines PC-3 and LNCaP. The serum levels of IL-6 in patients with prostate cancer and healthy controls,and the supernatants of prostate cancer cell cultures were measured by using ELISA. Results The IL-6 protein levels in prostate cancer tissue and PC-3 cells were significantly higher than those in adjacent benign prostatic tissue and LNCaP cells. The serum IL-6 levels in the patients with prostate cancer were markedly higher than those in the healthy controls. The IL-6 levels in supernatants in PC-3 cells were notably higher than those in the LNCaP cells. Conclusion The IL-6 gene may act as an important regulator in prostate cancer progression and may be one of the causes of prostate cancer conversion from an initially androgen-dependent state into an androgen-independent state.

Objective:To study the expression and correlation of interleukin-6 (IL-6), IL-6 receptor (IL-6R) and vascular endothelial growth factor C (VEGF-C) in the prostate cancer, and to investigate the relationship be-bent assay (ELISA) was used for detection of the expression level of IL-6 and IL-6R in 26 eases prostate cancer cantly higher than those in their adjacent tissues with a positive correlation between IL-6 and IL-6R levels (P< icantly associated with the lymphatic invasion and metastases in prostate cancer. Examination of VEGF-C expres-sion may be beneficial in the prediction of pelvic lymph node metastasis of prostate cancer.