Noise Reduction in Resource-Coupled Multi-Module Gene Circuits through Antithetic Feedback Control.

Gene circuits within the same host cell often experience coupling, stemming from the competition for limited resources during transcriptional and translational processes. This resource competition introduces an additional layer of noise to gene expression. Here we present three multi-module antithetic control strategies: negatively competitive regulation (NCR) controller, alongside local and global controllers, aimed at reducing the gene expression noise within the context of resource competition. Through stochastic simulations and fluctuation-dissipation theorem (FDT) analysis, our findings highlight the superior performance of the NCR antithetic controller in reducing noise levels. Our research provides an effective control strategy for attenuating resource-driven noise and offers insight into the development of robust gene circuits.

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

OBJECTIVES: Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). METHODS: This study included young adult patients aged 18-40 years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. RESULTS: A total of 300 RCC patients aged 18-40 years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4 ± 6.1 years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p < 0.001). There was no statistically significant difference observed in overall survival (OS) (p = 0.069). Pathological stage was a significant independent predictor for OS (p = 0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p = 0.020; p = 0.005). CONCLUSIONS: The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Proteome characterization of liver-kidney comorbidity after microbial sepsis.

Sepsis is a life-threatening condition that occurs when the body responds to an infection but subsequently triggers widespread inflammation and impaired blood flow. These pathologic responses can rapidly cause multiple organ dysfunction or failure either one by one or simultaneously. The fundamental common mechanisms involved in sepsis-induced multiple organ dysfunction remain unclear. Here, employing quantitative global and phosphoproteomics, we examine the liver's temporal proteome and phosphoproteome changes after moderate sepsis induced by cecum ligation and puncture. In total, 4593 global proteins and 1186 phosphoproteins according to 3275 phosphosites were identified. To characterize the liver-kidney comorbidity after sepsis, we developed a mathematical model and performed cross-analyses of liver and kidney proteome data obtained from the same set of mice. Beyond immune response, we showed the commonly disturbed pathways and key regulators of the liver-kidney comorbidity are linked to energy metabolism and consumption. Our data provide open resources to understand the communication between the liver and kidney as they work to fight infection and maintain homeostasis.

Context-dependent redesign of robust synthetic gene circuits.

Cells provide dynamic platforms for executing exogenous genetic programs in synthetic biology, resulting in highly context-dependent circuit performance. Recent years have seen an increasing interest in understanding the intricacies of circuit-host relationships, their influence on the synthetic bioengineering workflow, and in devising strategies to alleviate undesired effects. We provide an overview of how emerging circuit-host interactions, such as growth feedback and resource competition, impact both deterministic and stochastic circuit behaviors. We also emphasize control strategies for mitigating these unwanted effects. This review summarizes the latest advances and the current state of host-aware and resource-aware design of synthetic gene circuits.

Neoadjuvant stereotactic ablative body radiotherapy combined with surgical treatment for renal cell carcinoma and inferior vena cava tumor thrombus: a prospective pilot study.

BACKGROUND: Surgical treatment for renal cell carcinoma (RCC) and inferior vena cava (IVC) tumor thrombus (TT) is difficult, and the postoperative complication rate is high. This study aimed to explore the safety and oncologic outcomes of neoadjuvant stereotactic ablative body radiotherapy (SABR) combined with surgical treatment for RCC and IVC-TT. METHODS: Patients with RCC and IVC-TTs were enrolled in this study. All patients received neoadjuvant SABR focused on the IVC at a dose of 30 Gy in 5 fractions, followed by 2 ~ 4 weeks of rest. Then, radical nephrectomy and IVC tumor thrombectomy were performed for each patient. Adverse effects, perioperative outcomes, and long-term prognoses were recorded. RESULTS: From June 2018 to January 2019, 8 patients were enrolled-4 with Mayo grade II TT and 4 with Mayo grade III TT. Four (50%) patients had complicated IVC wall invasion according to CT/MRI. All patients received neoadjuvant SABR as planned. Short-term local control was observed in all 8 patients. Only Grade 1-2 adverse events were reported. In total, 3 (37.5%) laparoscopic surgeries and 5 (62.5%) open surgeries were performed. The median operation time was 359 (IQR: 279-446) min, with a median intraoperative bleeding volume of 750 (IQR: 275-2175) ml. The median postoperative hospital stay was 7 (5-10) days. With a 26-month (range: 5-41) follow-up period, the estimated mean overall survival was 30.67 ± 5.38 months. CONCLUSIONS: This is the first preoperative radiotherapy study in Asia that focused on patients with TT. This study revealed the considerable safety of neoadjuvant SABR for RCC with IVC-TT. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trials Registry on 2018-03-08 (ChiCTR1800015118). For more information, please see the direct link ( https://www.chictr.org.cn/showproj.html?proj=25747 ).

Anomalously bright single-molecule upconversion electroluminescence.

Efficient upconversion electroluminescence is highly desirable for a broad range of optoelectronic applications, yet to date, it has been reported only for ensemble systems, while the upconversion electroluminescence efficiency remains very low for single-molecule emitters. Here we report on the observation of anomalously bright single-molecule upconversion electroluminescence, with emission efficiencies improved by more than one order of magnitude over previous studies, and even stronger than normal-bias electroluminescence. Intuitively, the improvement is achieved via engineering the energy-level alignments at the molecule-substrate interface so as to activate an efficient spin-triplet mediated upconversion electroluminescence mechanism that only involves pure carrier injection steps. We further validate the intuitive picture with the construction of delicate electroluminescence diagrams for the excitation of single-molecule electroluminescence, allowing to readily identify the prerequisite conditions for producing efficient upconversion electroluminescence. These findings provide deep insights into the microscopic mechanism of single-molecule upconversion electroluminescence and organic electroluminescence in general.

Enhancing circuit stability under growth feedback with supplementary repressive regulation.

The field of synthetic biology and biosystems engineering increasingly acknowledges the need for a holistic design approach that incorporates circuit-host interactions into the design process. Engineered circuits are not isolated entities but inherently entwined with the dynamic host environment. One such circuit-host interaction, 'growth feedback', results when modifications in host growth patterns influence the operation of gene circuits. The growth-mediated effects can range from growth-dependent elevation in protein/mRNA dilution rate to changes in resource reallocation within the cell, which can lead to complete functional collapse in complex circuits. To achieve robust circuit performance, synthetic biologists employ a variety of control mechanisms to stabilize and insulate circuit behavior against growth changes. Here we propose a simple strategy by incorporating one repressive edge in a growth-sensitive bistable circuit. Through both simulation and in vitro experimentation, we demonstrate how this additional repressive node stabilizes protein levels and increases the robustness of a bistable circuit in response to growth feedback. We propose the incorporation of repressive links in gene circuits as a control strategy for desensitizing gene circuits against growth fluctuations.

Prevention, incidence, and risk factors of chyle leak after radical nephrectomy and thrombectomy.

BACKGROUND: To define the incidence and risk factors of chyle leak (CL) after radical nephrectomy and thrombectomy and to determine the impact of chyle leak on oncological outcomes. PATIENTS AND METHODS: A total of 445 patients who underwent radical nephrectomy and thrombectomy between January 2014 and January 2023 were included. CL is defined as the drainage of chyle with a triglyceride level greater than 110 mg/dL after oral intake or enteral nutrition. Multivariate logistic regression analysis was performed to identify the risk factors of postoperative (CL). The Kaplan-Meier curves were used to compare overall survival and cancer-specific survival. RESULTS: 44 patients (9.9%) were diagnosed as (CL). All patients developed CL within 6 days after the operation with a median time of 3 days. In multivariate logistic regression analysis, Mayo grade and side were independent patient-related risk factors. In addition, operation approach, operation time, and number of lymph nodes harvested were independent surgery-related risk factors. Between the CL group and the non-CL group, neither overall survival nor cancer-specific survival showed statistical differences. CONCLUSION: Based on this retrospective study of renal cell carcinoma and tumor thrombus patients in our center, we found that the risk factors were Mayo grade, side, operation approach, operation time, and number of lymph nodes harvested, and the occurrence of CL significantly prolonged hospital stay, but had no effect on long-term oncological outcomes.

Back focal plane imaging for light emission from a tunneling junction in a low-temperature ultrahigh-vacuum scanning tunneling microscope.

We report the design and realization of the back focal plane (BFP) imaging for the light emission from a tunnel junction in a low-temperature ultrahigh-vacuum (UHV) scanning tunneling microscope (STM). To achieve the BFP imaging in a UHV environment, a compact "all-in-one" sample holder is designed and fabricated, which allows us to integrate the sample substrate with the photon collection units that include a hemisphere solid immersion lens and an aspherical collecting lens. Such a specially designed holder enables the characterization of light emission both within and beyond the critical angle and also facilitates the optical alignment inside a UHV chamber. To test the performance of the BFP imaging system, we first measure the photoluminescence from dye-doped polystyrene beads on a thin Ag film. A double-ring pattern is observed in the BFP image, arising from two kinds of emission channels: strong surface plasmon coupled emissions around the surface plasmon resonance angle and weak transmitted fluorescence maximized at the critical angle, respectively. Such an observation also helps to determine the emission angle for each image pixel in the BFP image and, more importantly, proves the feasibility of our BFP imaging system. Furthermore, as a proof-of-principle experiment, electrically driven plasmon emissions are used to demonstrate the capability of the constructed BFP imaging system for STM induced electroluminescence measurements. A single-ring pattern is obtained in the BFP image, which reveals the generation and detection of the leakage radiation from the surface plasmon propagating on the Ag surface. Further analyses of the BFP image provide valuable information on the emission angle of the leakage radiation, the orientation of the radiating dipole, and the plasmon wavevector. The UHV-BFP imaging technique demonstrated here opens new routes for future studies on the angular distributed emission and dipole orientation of individual quantum emitters in UHV.

Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus.

Hepatitis B Virus (HBV) core protein allosteric modulators (CpAMs) are an attractive class of potential anti-HBV therapeutic agents. Here we describe the efforts toward the discovery of a series of 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (THPP) compounds as HBV CpAMs that effectively inhibit a broad range of nucleos(t)ide-resistant HBV variants. The lead compound 45 demonstrated inhibition of HBV DNA viral load in a HBV AAV mouse model by oral administration.

Causal inference between rheumatoid arthritis and prostate cancer.

It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.

Growth Feedback Confers Cooperativity in Resource-Competing Synthetic Gene Circuits.

Modularity is a key concept in designing synthetic gene circuits, as it allows for constructing complex molecular systems using well-characterized building blocks. One of the major challenges in this field is that these modular components often do not function as expected when assembled into larger circuits. One of the major issues is caused by resource competition, where multiple genes in the circuit compete for the same limited cellular resources, such as transcription factors and ribosomes. In addition, the mutual inhibition between synthetic gene circuits and cell growth results in growth feedback that significantly impacts its host-circuit dynamics. However, the complexity of the gene circuit dynamics under intertwined resource competition and growth feedback is not fully understood. This study developed a theoretical framework to examine the dynamics of synthetic gene circuits by considering both growth feedback and resource competition. Our results suggest a cooperative behavior between resource-competing gene circuits under growth feedback. Cooperation or competition is non-monotonically determined by the metabolic burden threshold. These two diverse effects could lead to the activation or deactivation of one circuit by the other. Lastly, the cooperativity mediated by growth feedback can attenuate the winner-takes-all resource competition. These findings show that coupling growth feedback and resource competition plays a crucial role in the dynamics of the host-circuit system, and understanding its effects helps control unexpected gene expression behaviors.

Long-term outcomes after cytoreductive nephrectomy and thrombectomy of patients with metastatic renal cell carcinoma with venous tumor thrombus: a retrospective study from a large Chinese center.

BACKGROUND: Targeted therapy combined with immunotherapy is the current first-line treatment for metastatic renal cell carcinoma (mRCC), but patients with tumor thrombus (TT) may suffer from lower limb edema or even sudden cardiac death, so the purpose of this study is to investigate the efficacy and safety of surgical treatment in patients with mRCC and TT and explore worse factors to affect the prognosis in this series of patients. PATIENTS AND METHODS: A total of 85 mRCC patients with TT who received cytoreductive nephrectomy and thrombectomy at our medical center from 2014 to 2023 are included. All patients received postoperative systemic therapy. Overall survival (OS) is defined as the time from surgery to death due to any reason or the last follow-up. Kaplan-Meier analysis was performed to evaluate OS and differences among groups were tested by log-rank. Multivariable Cox proportional hazards analysis was performed to ascertain independent relationships between clinicopathological factors and OS. RESULTS: The median age of patients was 58 years old. Eleven patients (12.9%) had no symptoms, 39 patients (45.9%) had local symptoms, 15 patients (17.6%) had systemic symptoms, and 20 patients (23.5%) had both. Mayo grade of TT was 0, 1, 2, 3, and 4 for 12, 27, 31, 7, and 8 patients respectively. Fifty-five patients had lung metastasis, 23 had bone metastasis, 16 had liver metastasis, 13 had adrenal metastasis, and 9 had lymph node metastasis. Of all patients, 17 patients had multiple metastases. The median operation time is 289 min and the median intraoperative hemorrhage is 800 ml. Twenty-eight patients experienced postoperative complications, 8 of which were serious complications of modified Clavien grade III or higher. The median OS of all patients was 33 months and median follow up time was 26 months. In multivariate analysis, systemic symptom (p = 0.00753), pathological type (p = 0.0166), sarcomatous degeneration (p = 0.0334), and perirenal fat infiltration (p = 0.0202) are independent predictors of OS. CONCLUSION: Cytoreductive nephrectomy and thrombectomy is relatively safe and effective for patients with mRCC accompanied by TT. In this series of patients, the worse prognosis is associated with systemic symptoms, non-clear cell carcinoma, sarcomatous degeneration and perirenal fat infiltration.

FOXM1/NCAPH activates glycolysis to promote colon adenocarcinoma stemness and 5-FU resistance.

Chemotherapy using 5-fluorouracil (5-FU) is currently considered the most effective treatment for advanced colon adenocarcinoma (COAD). However, drug resistance remains a major obstacle in treating COAD. Non-SMC condensin I complex subunit H ( NCAPH ) is known to have a certain impact on the development of COAD, but its precise involvement in the mechanism of 5-FU resistance has not been demonstrated. Bioinformatics analysis was utilized to assay the expression of NCAPH and Forkhead box M1 ( FOXM1 ) in COAD tumor tissues, which was then verified in COAD cell lines. The resistance of COAD cells to 5-FU was measured by CCK-8 assay, stemness was tested by cell sphere formation assay, and glycolysis ability was measured by cellular energy analysis metabolism. Chromatin Immunoprecipitation and dual-luciferase reporter assays were done to confirm the specific interaction between FOXM1 and NCAPH . The expression levels of FOXM1 and NCAPH were significantly upregulated in COAD tissues and cells, and they were involved in regulating the glycolytic signaling pathway. Inhibition of the glycolytic pathway could reverse the effect of NCAPH overexpression on COAD stemness and resistance. FOXM1 was identified as a transcription factor of NCAPH , and it regulated COAD glycolysis, cell stemness, and 5-FU resistance by activating NCAPH expression. FOXM1-mediated upregulation of NCAPH expression promoted COAD cell stemness and resistance via the glycolytic pathway. This study provides a possible mechanism for the FOXM1/NCAPH axis in the glycolytic pathway, cell stemness, and resistance in COAD.

Effects of growth feedback on gene circuits: A dynamical understanding.

The successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit-host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifying topologies resilient to growth feedback are crucial for both fundamental and applied research. Utilizing transcriptional regulation circuits with adaptation as a paradigm, we systematically study 435 distinct topological structures and uncover six categories of failures. Three dynamical mechanisms of circuit failures are identified: continuous deformation of the response curve, strengthened or induced oscillations, and sudden switching to coexisting attractors. Our extensive computations also uncover a scaling law between a circuit robustness measure and the strength of growth feedback. Despite the negative effects of growth feedback on the majority of circuit topologies, we identify a few circuits that maintain optimal performance as designed, a feature important for applications.

Cephalic inferior vena cava non-clamping technique versus standard procedure for robot-assisted laparoscopic level II-III thrombectomy: a prospective cohort study.

BACKGROUND: Renal tumour can invade the venous system and ~4-10% patients with renal tumour had venous thrombus. Although the feasibility of robot-assisted laparoscopic inferior vena cava thrombectomy (RAL-IVCT) in patients with inferior vena cava (IVC) thrombus has been validated, the wide application is still a challenge due to the complexity of IVC control. The objective was to describe our novel cephalic IVC non-clamping technique and to compare the outcomes versus standard RAL-IVCT. MATERIALS AND METHODS: A prospective single-centre cohort containing 30 patients with level II-III IVC thrombus was established since August 2020. Fifteen patients underwent cephalic IVC non-clamping approach and 15 patients received standard RAL-IVCT. The authors decided the surgical technique according to the echocardiographic assessment of the right heart and IVC. RESULTS: The non-clamping group had less operative time (median 148 versus 185 min, P =0.04), and lower Clavien-grade II complication rate (26.7% versus 80.0%, P =0.003). The median intraoperative blood loss were 400 ml [interquartile range (IQR) 275-615 mL] and 800 ml (IQR 350-1300 ml), respectively ( P =0.05). The most common complication in standard RAL-IVCT group was liver dysfunction. No gas embolism, hypercapnia or tumour thrombus dislodgment occurred in non-clamping group. After a median follow-up of 17.0 months (IQR 13.5-18.5 months) and 15.5 months (IQR 13.0-17.0 months), two patients (16.7%) in the non-clamping group and 3 patients (20.0%) in the standard RAL-IVCT group died (hazard ratio 0.59, 95% CI 0.10-3.54, P =0.55). CONCLUSIONS: The cephalic IVC non-clamping technique can be performed safely with acceptable surgical outcomes and short-term oncologic outcomes in patients with level II-III IVC thrombus. Compared with standard procedure, it had less operative time and lower complication rate.

Influence of physicians' seniority on efficacy of silver needle therapy for low back fasciitis: A prospective, cohort study.

BACKGROUND: Physicians' seniority has always been the focus of patients. Silver needle therapy (SNT) has been applied for more than 60 years. It is similar to moxibustion and has a good therapeutic effect on soft tissue pain. This study aimed to determine the influence of physicians' seniority on the efficacy of SNT for patients with low back fasciitis. METHODS: This was a prospective cohort study at the Affiliated Hospital of Qingdao University. Patients diagnosed with low back fasciitis were split into junior physician (JP) and senior physician (SP) groups (n = 30) based on the seniority of the physician. The numerical rating scale (NRS) was administered during the SNT, and operation time was recorded. The NRS, Oswestry Disability Index (ODI), and Short-Form 12 of quality of life (SF-12) scores at 1, 2, 6, and 12 months after the treatment and autonomic nervous system (ANS) activity were also observed. RESULTS: Compared with the SP group, the NRS score during the SNT (5.20 ±â€…0.71 vs 2.53 ±â€…0.94) and operation time (11.7 ±â€…1.6 minutes vs 6.8 ±â€…1.1 minute) were higher in the JP group (P < .05). The NRS, ODI score, SF-12 score, and ANS activity after treatment were not significantly different between SP and JP groups. Additionally, in the multivariate linear regression analysis model, the physicians' seniority was an independent factor affecting the NRS score during the SNT and operation time (P < .05). CONCLUSION: SNT could attenuate the pain of patients with low back fasciitis in the short and long term without severe complications. The physicians' seniority did not influence the efficacy of SNT, but the JP group showed an increased operation time and a higher degree of pain during the operation.

Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique in Right Nephrectomy and Inferior Vena Cava Tumor Thrombectomy: A Novel Surgical Technique and Long-Term Outcomes from a Large Chinese Center.

Purpose: To explore the safety and effectiveness of the Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique (PREP-IT) in laparoscopic radical nephrectomy (LRN) and inferior vena cave (IVC) tumor thrombectomy for right renal-cell carcinoma (RCC) with level Mayo I to III venous tumor thrombus (VTT). Patients and Methods: From May 2015 to September 2020, 92 patients with right RCC and Mayo I to III VTT were retrospectively reviewed, including 57 patients who underwent retroperitoneal LRN and IVC thrombectomy using PREP-IT, and 35 patients who underwent open surgery. PREP-IT refers to dissecting the retroperitoneum and temporarily placing the right kidney into the abdominal cavity to enlarge the retroperitoneal workspace for a safer and faster IVC operation. Results: Compared with the open surgery group, the PREP-IT group had a larger tumor diameter, while a larger proportion of Mayo I tumor thrombus and smaller maximum tumor thrombus width. Two patients (3.5%) in the PREP-IT group had a history of abdominal surgery. No conversion to open surgery or standard laparoscopic surgery occurred in PREP-IT group. Laparoscopic surgery with PREP-IT was characterized by shorter operative time, less surgical blood loss, shorter postoperative hospital stay, and lower postoperative complication rate. With a 33-month (ranges: 2-86) follow-up time period, the estimated mean overall survival time was 57.2 ± 5.3 and 58.1 ± 71.5 months in the PREP-IT group and open surgery group, respectively. Log-rank test indicated no significant difference between the two groups in terms of overall survival and cancer-specific survival. Conclusions: The PREP-IT is relatively safe and feasible for retroperitoneal LRN with right renal tumor and IVC tumor thrombus, allowing for a large workspace and wide exposure for IVC operations.

Systemic lupus erythematosus and prostate cancer risk: a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Current observational studies suggest that there may be a causal relationship between systemic lupus erythematosus (SLE) and prostate cancer (PC). However, there is contradictory evidence. This study aimed to investigate and clarify the association between SLE and PC. METHODS: We searched PubMed, Embase, Web of Science, and Scopus until May 2022. A meta-analysis was conducted on the standard incidence rate (SIR) and 95% CI. Subgroup analysis was performed based on the follow-up duration, study quality, and appropriate SLE diagnosis. Mendelian randomization (MR) of the two samples was used to determine whether genetically elevated SLE was causal for PC. Summary MR data were obtained from published GWASs, which included 1,959,032 individuals. The results were subjected to sensitivity analysis to verify their reliability. RESULTS: In a meta-analysis of 79,316 participants from 14 trials, we discovered that patients with SLE had decreased PC risk (SIR, 0.78; 95% CI, 0.70-0.87) significantly. The MR results showed that a one-SD increase in genetic susceptibility to SLE significantly reduced PC risk (OR, 0.9829; 95% CI, 0.9715-0.9943; P = 0.003). Additional MR analyses suggested that the use of immunosuppressants (ISs) (OR, 1.1073; 95% CI, 1.0538-1.1634; P < 0.001), but not glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs), which were associated with increased PC risk. The results of the sensitivity analyses were stable, and there was no evidence of directional pleiotropy. CONCLUSIONS: Our results suggest that patients with SLE have a lower risk of developing PC. Additional MR analyses indicated that genetic susceptibility to the use of ISs, but not GCs or NSAIDs, was associated with increased PC risk. This finding enriches our understanding of the potential risk factors for PC in patients with SLE. Further study is required to reach more definitive conclusions regarding these mechanisms.