Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Complexity study on the Cournot-Bertrand mixed duopoly game model with market share preference.

In this paper, a Cournot-Bertrand duopoly model with market share preference is established. Assume that there is a degree of product difference between the two firms, where one firm takes the price as a decision variable and the other takes the quantity. Both firms are bounded rational, with linear cost functions and demand functions. The stability of the equilibrium points is analyzed, and the effects of some parameters (α, ß, d and v1) on the model stability are studied. Basins of attraction are investigated and the evolution process is shown with the increase in the output adjustment speed. The simulation results show that instability will lead to the increase in the average utility of the firm that determines the quantity and reduce the average utility of the firm that determines price.

CAB39 promotes cisplatin resistance in bladder cancer via the LKB1-AMPK-LC3 pathway.

Systemic therapy for muscle-invasive bladder cancer (BC) remains dominated by cisplatin-based chemotherapy. However, resistance to cisplatin therapy greatly limits long-term survival. Resistance to cisplatin-based chemotherapy still needs to be addressed. In this study, we established three cisplatin-resistant BC cell lines by multiple cisplatin pulse treatments. Interestingly, after exposure to cisplatin, all cisplatin-resistant cell lines showed lower reactive oxygen species (ROS) levels than the corresponding parental cell lines. Using proteomic analysis, we identified 35 proteins that were upregulated in cisplatin-resistant BC cells. By knocking down eleven of these genes, we found that after CAB39 knockdown, BC cisplatin-resistant cells were more sensitive to cisplatin. Overexpression of CAB39 had the opposite effect. Then, the knockdown of six genes downstream of CAB39 revealed that CAB39 promoted cisplatin resistance in BC through LKB1. Moreover, a key cause of cisplatin-induced cell death is damage to mitochondria and increased ROS levels. In our study, cisplatin-resistant cells exhibited higher autophagic flux and healthier mitochondrial status after cisplatin exposure. We demonstrated that the CAB39-LKB1-AMPK-LC3 pathway plays a critical role in enhancing autophagy to maintain the health of mitochondria and reduce ROS levels. In addition, the autophagy inhibitor chloroquine (CQ) can significantly enhance the killing effect of cisplatin on BC cells. Compared with gemcitabine plus cisplatin (GC), GC plus CQ significantly reduced tumor burden in vivo. In conclusion, our study shows that CAB39 counteracts the killing of cisplatin by enhancing the autophagy of BC cells to damaged mitochondria and other organelles to alleviate the damage of cells caused by harmful substances such as ROS.

Perioperative, functional, and oncologic outcomes of minimally-invasive surgery for highly complex renal tumors (RENAL or PADUA score ≥ 10): an evidence-based analysis.

The primary objective of the current study is to undertake a comparative analysis of the effectiveness and safety of minimally-invasive partial nephrectomy (MIPN; including laparoscopic and robotic approaches) and open partial nephrectomy (OPN) for the treatment of highly complex renal tumors (defined as PADUA or RENAL score ≥ 10). A comprehensive search was conducted in four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) to identify relevant studies published in the English language up to April 2023. The current study employed Review Manager 5.4 and encompassed controlled trials of both MIPN and OPN for the treatment of highly complex renal tumors. This study comprised a total of eight comparative trials involving 1161 patients. MIPN demonstrated a significant reduction in length of hospital stay (weighted mean difference [WMD] - 2.08 days, 95% confidence interval [CI] - 2.48, - 1.68; p < 0.00001), blood loss (WMD - 39.86 mL, 95% CI - 75.32, - 4.39; p = 0.03), transfusion rates (odds ratio [OR] 0.30, 95% CI 0.13, 0.71; p = 0.006), and overall complications (OR 0.46, 95% CI 0.31, 0.70; p = 0.0003). However, there were no significant differences between MIPN and OPN in terms of operative time, warm ischemia time, conversion to radical nephrectomy rates, renal functional and oncologic outcomes. This study reveals that MIPN presents several benefits in comparison to OPN, including decreased length of hospital stay, blood loss, transfusion rates, and complications, while still offering renal functional and oncological outcomes that are comparable to those of OPN in patients with highly complex renal tumors.

Price game and chaos control among three oligarchs with different rationalities in property insurance market.

Combining with the actual competition in Chinese property insurance market and assuming that the property insurance companies take the marginal utility maximization as the basis of decision-making when they play price games, we first established the price game model with three oligarchs who have different rationalities. Then, we discussed the existence and stability of equilibrium points. Third, we studied the theoretical value of Lyapunov exponent at Nash equilibrium point and its change process with the main parameters' changes though having numerical simulation for the system such as the bifurcation, chaos attractors, and so on. Finally, we analyzed the influences which the changes of different parameters have on the profits and utilities of oligarchs and their corresponding competition advantage. Based on this, we used the variable feedback control method to control the chaos of the system and stabilized the chaos state to Nash equilibrium point again. The results have significant theoretical and practical application value.

Study on complex dynamics for the waste electrical and electronic equipment recycling activities oligarchs closed-loop supply chain.

Nowadays, with more and more WEEE (waste electrical and electronic equipment) being abandoned, WEEE recycling activities are increasingly popular. In this paper, we build a closed-loop supply chain model and focus on the recycling behaviors of the members in this supply chain, which contains two manufacturers, the retailer, and the consumer. In the reverse chain, we set up dual channels and design two recycling methods: sell-back method and trade-in method. We use classical backward induction to run the model. And then we analyze the stability of the system and the impacts of some essential parameters by numerical simulation. The speed of the manufacture's decision adjustment has a significant effect on the stability of the model. Manufacturers should adopt a stable rather than radical price adjustment strategy in order to achieve stable profit growth in the whole supply chain and avoid a chaotic price war. Manufacturers should increase innovation investment in recycling technology to reduce the cost of remanufacturing products and improve the initiative in market competition. In the end, we adopt the parameter control method and the decision-making method to control chaos, and they both have a good control effect.

Research on equilibrium strategy and emergency management of three oligarch battery manufacturers under cooperative promotion and low-carbon policy.

People are increasingly paying much attention to battery technology, especially the zinc-nickel battery and the lithium battery, for solving energy shortages and environmental contamination. Meanwhile, the drastic change in the external outside environment has brought a huge challenge to manage the battery industry chain. Therefore, in the uncertain external environment, the study of supply chain competition between lithium battery and new nickel battery manufacturers is the focus of this paper. We build a cooperative game model under the demand disturbance and a non-cooperative game under the background of product promotion. The results show that (i) the price set by the manufacturer increases with technical improvement when consumers are more sensitive to the technical level. (ii) The optimal price of all manufacturers will drop as the CETRC (carbon emission technology renewal coefficient) increases. (iii) The price of zinc-nickel batteries will be higher than that of lithium battery as the market promotion rate is in the middle range. In the model, the supply chain determines different optimal prices according to the different ranges of the demand disturbance.

Identifying Lockdown Relaxation Strategies and Policy Implications to Fight against COVID-19: Medical Experts Perspective from Pakistan.

The COVID-19 pandemic, was first identified in Wuhan, China, has had a drastic effect on the world economy and compelled governments to enforce lockdown in territories. However, lockdown is destroying the world economy badly as well as the physical and mental health of people. Therefore, governments must develop Lockdown Relaxation Strategies (LRS) to overcome the negative consequences of lockdown in Pakistan. Identifying LRS is important for public health and economic restoration. Therefore, this work is an initial attempt to develop LRS in a developing country - Pakistan, and prioritize LRS through a novel ISM-MICMAC approach. By taking response from experts, results show that implementation of smart lockdowns in affected areas, meeting minimum criteria of public health standards, limited operations of public transportation are the most important strategies. Results provide a strategic guideline for governments to take necessary measures and allocate resources appropriately.

Sustainable construction through energy management practices: an integrated hierarchal framework of drivers in the construction sector.

Reducing energy usage and promoting energy management practices remain hot issues in the construction sector. Construction firms are not interested to adopt energy conservation and management practices in their projects. Despite the successful integration of energy management practices in developed nations, their adaptability in developing countries, especially in Pakistan, is at a slow pace. Therefore, drivers to energy management practices need to be realized for its adoption. Based on this, the current study intends to evaluate the drivers of energy management practices adopted in the construction sector of Pakistan by using a four-stage methodology. Fuzzy Delphi method (FDM), interpretive structural modeling (ISM), and Matrice d'Impacts Croises Multiplication Appliques a un Classement (MICMAC) analysis were integrated with prioritizing essential drivers. Increased tax imposition on construction companies for energy usage and pollution contribution, promotion of investment subsidies for energy efficiency technologies, and increased enforcement of government rules and regulations regarding on-site energy management practices arose as significant drivers to adoption of energy management practices in the construction sector of Pakistan. These results will be helpful for policymakers to develop effective policies for integrating energy management practices in the construction sector. This study contributes significantly by developing a novel model of drivers affecting EMP adoption in the Pakistani construction sector. Further research might be expanded to other developing countries to validate current results.

Sustainable construction through energy management practices in developing economies: an analysis of barriers in the construction sector.

In the recent era, energy management practices (EMPs) have gained significant importance in developed countries, due to their cost efficiency and the potential to protect the environment. However, developing countries are not particularly serious about adopting and implementing sustainable construction practices, due to the different barriers that hinder them from doing so. Therefore, the complete adoption of effective EMPs is still at the initial stage. The objective of this study is to identify the barriers to EMPs adoption, in the construction sector of Pakistan. Initially, the barriers were identified from the earlier studies and screened by the fuzzy Delphi method (FDM). These screened barriers were then evaluated through the ISM. The results of the ISM show that there happens to be a "lack of communication and collaboration among project stakeholders," "attitudinal, cultural and behavioral resistance to adopt EMPs", "lack of top management support and interest in energy management issues," "no condition for implementing EMPs on construction site," and "lack of financing schemes to implement energy management technology," as the top barriers to EMPs adoption in the construction projects pertaining to Pakistan. Thus in this regard, this study empirically contributes to EMPs literature that is based on the developing countries and supports the policymakers in developing appropriate strategies to reduce energy consumption in construction projects-especially in developing countries.

Y-Box Binding Protein 1 Regulates Angiogenesis in Bladder Cancer via miR-29b-3p-VEGFA Pathway.

Angiogenesis plays a vital role in the development of bladder cancer (BC). The Y-box-binding protein 1 (YB-1) is a well-known oncoprotein which is closely related to angiogenesis of tumors, but the relationship and mechanism of YB-1 and angiogenesis in BC remain unclear. Based on 56 clinical BC specimens, this study found that high expression of YB-1 samples demonstrated a higher expression of vascular endothelial growth factor A (VEGFA) than those of YB-1 low expression. Subsequently, the expression of YB-1 and miR-29b-3p was regulated in the BC cell lines where we noted that YB-1 promoted VEGFA expression by downregulating the expression of miR- 29b-3p. The ability of BC cells to induce angiogenesis decreased after YB-1 was knocked down. Moreover, the in vivo study further confirmed that YB-1 promotes angiogenesis in BC. Our findings enhance the understanding of how YB-1 promotes angiogenesis in BC and provide evidence for YB-1 as a therapeutic target of BC. Moreover, this may provide new inspiration for miRNAs replacement therapies.

Testicular Metastasis from Urothelial Carcinoma of the Renal Pelvis: A Rare Case and Review of the Literature.

This paper presents an extremely rare case of testicular metastasis arising from renal pelvis carcinoma. The testicle is a rare site of clinically detectable tumor metastasis, originating rarely from upper tract urothelial carcinoma (UTUC). There are only two cases concerning UTUC metastasis to the testis available in the literature. In this report, we presented a patient who developed serial testicle, lung, liver and retroperitoneal lymph node metastasis from primary urothelial carcinoma of the renal pelvis within one year after surgery and chemotherapy. In conclusion, for patients with a history of UTUC who present with testicular symptoms, clinicians should be highly alert for the possibility of malignant involvement at this site.

Melamine Poisoning Pediatric Urolithiasis Treatment in Gansu, China 5-Year Follow-up Analysis.

OBJECTIVE: To investigate the clinical characteristics of urolithiasis, retrospectively, in children who ingested melamine-poisoned formula as infants, and report a 5-year follow-up analysis. MATERIALS AND METHODS: Clinical data on 207 patients (mean ± standard deviation, 13.6 ± 8.0 months) with melamine-induced urolithiasis were retrospectively analyzed. Patients were subdivided into 2 groups according to treatment. A 5-year follow-up study was conducted with 95.7% (198 of 207) of the children. Ultrasonography, renal function evaluation, and urinalysis were analyzed. RESULTS: A total of 149 (72.0%) patients accepted conservative treatment. Fifty-eight (28.0%) patients accepted surgical intervention after conservative treatment proved ineffective. Of the 48 patients in whom retrograde ureteral catheterization was performed, 33 discharged the stone successfully, 4 had residual stones, 2 were switched to percutaneous nephrolithotripsy, and 9 underwent ureteroscopic lithotripsy. Six patients underwent extracorporeal shock wave lithotripsy, and other 4 patients underwent ureteral lithectomy. The age of onset, clinical presentations, size and location of stones, renal function, and mean time of hospitalization in patients with surgical intervention were significantly different from those of patients who accepted conservative treatment only (P < .001). The main component of the 12 melamine-contained stone samples was urate. The results of 5-year follow-up (mean ± standard deviation, 72.7 ± 4.1 months) study in 198 children did not show any significant difference of stone residue, renal function, and urinalysis between 2 groups. CONCLUSION: If the stones were treated appropriately in patients with melamine-induced urolithiasis, there is no medium-term risk for stone formation. Still, a longer time follow-up study is required to determine if there is any long-term poisonous effect on these patients.

Calcium Oxalate Induces Renal Injury through Calcium-Sensing Receptor.

Objective. To investigate whether calcium-sensing receptor (CaSR) plays a role in calcium-oxalate-induced renal injury. Materials and Methods. HK-2 cells and rats were treated with calcium oxalate (CaOx) crystals with or without pretreatment with the CaSR-specific agonist gadolinium chloride (GdCl3) or the CaSR-specific antagonist NPS2390. Changes in oxidative stress (OS) in HK-2 cells and rat kidneys were assessed. In addition, CaSR, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 expression was determined. Further, crystal adhesion assay was performed in vitro, and the serum urea and creatinine levels and crystal deposition in the kidneys were also examined. Results. CaOx increased CaSR, ERK, JNK, and p38 protein expression and OS in vitro and in vivo. These deleterious changes were further enhanced upon pretreatment with the CaSR agonist GdCl3 but were attenuated by the specific CaSR inhibitor NPS2390 compared with CaOx treatment alone. Pretreatment with GdCl3 further increased in vitro and in vivo crystal adhesion and renal hypofunction. In contrast, pretreatment with NPS2390 decreased in vitro and in vivo crystal adhesion and renal hypofunction. Conclusions. CaOx-induced renal injury is related to CaSR-mediated OS and increased mitogen-activated protein kinase (MAPK) signaling, which subsequently leads to CaOx crystal adhesion.

Studies on chemical modification and biology of a natural product, gambogic acid (II): Synthesis and bioevaluation of gambogellic acid and its derivatives from gambogic acid as antitumor agents.

Gambogic acid (GA) has been reported to be a potent apoptosis inducer. The fact that it is amenable to chemical modification makes GA an attractive molecule for the development of anticancer agents. We firstly reported the synthesis of gambogellic acid, which was generated under acid catalysis from readily available GA by a base-catalyzed diene intramolecular annelation. Sequentially, thirteen new compounds were synthesized and their inhibitory activity on HT-29, Bel-7402, BGC-823, and A549 cell lines were evaluated in vitro by MTT assay, and (38, 40)-epoxy-33-chlorogambogellic acid (4) was identified as a BGC-823 cell apoptosis inducer through MTT cell assay, observations of morphological changes, and Annexin-V/PI double-staining assay. Compound 4 showed significant effects in inducing apoptosis and might serve as a potential lead compound for discovery of new anticancer drugs. Further structure-activity relationships (SARs) of gambogic acid derivatives were discussed.