ABSTRACT Nephrolithiasis is increasingly prevalent worldwide. Although metabolic dysregulation has emerged as an important feature of the disease, the specific metabolic programs within tubular epithelial cells that drive stone formation remain poorly understood. Here, we use single‐cell transcriptomics to profile mouse models of nephrolithiasis and identify a marked suppression of gluconeogenesis in renal proximal tubular epithelial cells, driven by downregulation of the rate‐limiting enzyme glucose‐6‐phosphatase (G6PC) and associated with lactate accumulation. We further show that loss of G6PC or lactate accumulation is sufficient to activate TGF‐β/SMAD3 signaling, driving epithelial–mesenchymal transition (EMT) and a profibrotic epithelial program associated with enhanced crystal deposition. Mechanistically, lactate induces lactylation of the transcription factor SNAIL1 at lysine 206, facilitating its nuclear localization and transcriptional activation of TGF‐β. Together, these findings establish a G6PC‐lactate‐SNAIL1 axis linking metabolic dysregulation to epithelial remodeling during nephrolithiasis.

Calcium oxalate (CaOx) nephrocalcinosis is a chronic kidney disease marked by CaOx crystal deposition, oxidative stress, neutrophil infiltration, and renal tubular epithelial cell injury. To date, no targeted therapies are clinically available for this condition. Antioxidant nanomaterials capable of scavenging excessive reactive oxygen species (ROS) offer a promising approach for treating CaOx crystal-induced kidney injury. Neutrophil-mediated delivery systems have been leveraged to transport nanomaterials to inflamed kidneys for acute kidney injury therapy, and their targeting specificity can be further augmented through the functionalization of cell membranes with targeting peptides. Herein, we developed a biomimetic nanoplatform by loading DNase I onto black phosphorus nanosheets (BPNSs) and coating them with a neutrophil membrane modified with a CD44-targeting peptide (PNM@D@BP), aiming to ameliorate renal CaOx crystal deposition and the consequent kidney injury. The engineered neutrophil membrane coating conferred the nanocarrier with the ability to home to sites of renal injury and inflammation. PNM@D@BP exhibited potent antioxidative activity, effectively eliminating CaOx crystal-induced ROS. In both in vivo and in vitro settings, PNM@D@BP was shown to suppress the formation of neutrophil extracellular traps (NETs). Moreover, RNA sequencing and bioinformatic analyses revealed that PNM@D@BP protects against CaOx crystal-induced kidney injury by modulating oxidative stress and neutrophil-driven inflammatory responses. Collectively, these findings underscore the therapeutic potential of PNM@D@BP for the treatment of CaOx kidney stones.

To investigate a novel intracorporeal minimally invasive procedure for robot assisted laparoendoscopic single-site partial nephrectomy. This study reported our technique and the outcomes of a minimally invasive approach for partial nephrectomy, specifically robotic laparoendoscopic single-site ultrasound-guided renal artery balloon catheter occluded hybrid partial nephrectomy (LESS-HPN). A Freeport for LESS was inserted through a 4.5–5.0 cm skin incision. Instead of the traditional renal artery clamping technique, a Fogarty balloon catheter was used to occlude the renal artery or its branch. Tumor resection and wound suturing was then performed as routine steps. A total of 10 patients with T1 stage renal tumors underwent successful LESS-HPN from March to July 2023, with no conversions to renal artery clamping or additional ports. The mean operative time was 103.3 ± 11.1 min, including 21.0 ± 2.7 min of warm ischemia time. The mean estimated blood loss was 42.0 ± 22.5 ml. Tumors located posteriorly were associated with shorter operative time compared to those located anteriorly (p = 0.041). Occlusion of the main renal arteries, branch arteries, and accessory renal artery was achieved in 7, 2 and 1 cases, respectively. During a median follow-up of 10.5 months, no recurrence, metastasis, or death was observed. Limitations of this study include the small sample size, the absence of a control group, and the relatively short follow-up duration. LESS-HPN has proven to be a safe and feasible alternative for achieving intracorporeal minimal invasiveness in patients with renal tumors. Clinical trials were registered in September 4th, 2021, available at www.chictr.org.cn/ (ChiCTR2100050808). This article belongs to a selection of patients who were part of this clinical study.

Lung cancer is the most common cancer type worldwide, and investigating novel therapeutics methods for the treatment of chemoresistant lung cancer are of notable clinical significance. Reverse transcription-quantitative polymerase chain reaction and western blotting assays were performed to analyze the expression levels of phosphatase and tensin homolog (PTEN) and microRNA-4328 (miR-4328), and Cell Counting Kit-8 (CCK-8) and Transwell migration assays were conducted to evaluate the proliferation and migration of A549 cells, respectively. Everolimus was observed to upregulate the expression of PTEN and inhibit the proliferation and migration of A549 cells in a dose-dependent manner. The knockdown of PTEN abolished the effects of everolimus on the proliferation and migration of A549 cells, and everolimus was demonstrated to upregulate PTEN, and inhibit the proliferation and migration of A549 cells via downregulating miR-4328. Collectively, the results of the present study indicate that everolimus inhibited the proliferation and migration of EGFR-resistant A549 lung cancer cells via regulating the miR-4328/PTEN signaling pathway.

Objectives: The advent of robotic-assisted partial nephrectomy (RAPN) has marked a new era in minimally invasive surgery, establishing itself as a preferred method for managing renal cell carcinoma (RCC). However, even within the same center, variations in the use of robotic arms during RAPN have been reported. In this study, we aim to explore differences in efficiency, safety, and hospital costs between three-arm and four-arm RAPN. Methods: This retrospective study analyzed the clinical data of 91 patients who underwent RAPN in Tongji Hospital from January 2021 to December 2023. The patients were divided into two groups: 50 patients in the three-arm group (with the use of three robotic arms and two assistant ports) and 41 patients in the four-arm group (with the use of four robotic arms and one assistant port). Patients’ demographics and tumor characteristics, operative outcomes, and hospital costs were recorded. Propensity score matching (1:1) was performed on age, gender, body mass index, laterality, RENAL score, tumor stage, and pathological grade. We compared three-arm with four-arm RAPN groups based on operative outcomes, and hospital costs. Results: In total, 50 and 41 patients underwent three-arm and four-arm RAPN. All procedures were successfully executed without the need to convert to open surgery or radical nephrectomy. After matching, the four-arm configuration demonstrated a numerically longer total operative time compared with the three-arm approach (146.5 vs. 120.0 min, p = 0.068). Hospital costs in the four-arm group were significantly higher than those in the three-arm group (76,922.5 vs. 68,406.7 CNY, p = 0.006). Conclusions: Both the three-arm and four-arm robotic approaches demonstrated comparable safety and efficacy in RAPN procedures. Nevertheless, the four-arm approach is associated with elevated hospital costs. The preliminary findings suggest potential cost containment disadvantages for the four-arm technique in selected cases, though larger multicenter studies are essential.

Cirrhotic liver nodules can progress to hepatocellular carcinoma (HCC) through a multi-step carcinogenesis model, with dysplastic nodules being particularly high risk. Currently, monitoring the progression of non-HCC cirrhotic nodules is primarily through dynamic observation, but there is a lack of sensitive, efficient, and convenient methods. Dynamic monitoring and risk evaluation of malignant transformation are essential for timely treatment and improved patient survival rates. Routine liver biopsies are impractical for monitoring, and imaging techniques like ultrasound, computed tomography, and magnetic resonance imaging are not suitable for all patients or for accurately assessing subcentimeter nodules. Identifying serum biomarkers with high sensitivity, specificity, and stability, and developing a multi-index evaluation model, may provide a more convenient and efficient approach to monitoring pathological changes in cirrhotic nodules.

Background:Conventional vascular interventions and hybrid surgery relied on digital subtraction angiography (DSA). Previously our center explored hybrid partial nephrectomy with DSA guidance, which demonstrates the superiority of omitting the dissection of renal hilum. However, this approach is limited to scarce hybrid operating rooms, involves radiation exposure, and poses compatibility issues with robotic surgery platforms. Laparoscopic ultrasound (LUS) can assist in robotic surgery. This study explored the application of LUS-guided occlusion of renal artery blood supply with a Fogarty balloon catheter, particularly in hybrid partial nephrectomy for renal tumor treatment. Case Description:The LUS-guided renal artery balloon catheter occluded hybrid partial nephrectomy (UBo-HPN) involved several steps: trans-femoral artery cannulation, placement of the balloon catheter into the renal artery via the femoral vascular sheath, occlusion of the renal blood supply by inflating the balloon catheter, completion of zero-ischemia partial nephrectomy with arterial flow occluded, withdrawal of the balloon catheter after deflation. For all three patients, the balloon catheter was successfully and accurately placed into the selected renal artery under LUS guidance. Intraoperative occlusion of the renal blood supply was confirmed to be complete and reversible. No complications were observed during follow-up. Conclusions:LUS guidance presents a safe alternative to DSA guidance for assisting in hybrid surgery. LUS-guided hybrid partial nephrectomy is safe and feasible.

One key focus of partial nephrectomy is preserving renal function. Segmental renal artery occlusion with microdissection at the renal hilum confines ischemia, effectively reducing warm ischemic injury. Ultrasound-Guided Renal Artery Balloon Catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN) can achieve branch occlusion without the need for dissecting the renal hilum. To investigate the feasibility and safety of UBo-HPN of branch renal artery occlusion in the treatment of localized renal tumors. A prospective single-arm analysis involving 20 patients with renal localized tumors underwent robot assisted UBo-HPN with branch renal artery occlusion from August 2021 to July 2023, with an average follow-up of 12 months. All patient was successfully operated on without conversion to conventional arterial clamping or radical nephrectomy. One case (5

Supplementary Figure 1: PTENP1 and PTEN expression were decreased in human ccRCC samples. Supplementary Figure 2: PTENP1 expression in ACHN and SN12PM6 cells. Supplementary Figure 3: PTENP1 expression activated AKT in ACHN and SN12PM6 cells. Supplementary Figure 4: miR-21 expression in ACHN and SN12PM6 cells. Supplementary Figure 5: PTEN expression in ACHN and SN12PM6 cells. Supplementary Figure 6: 5-10 fold overexpression of PTENP1 increased PTEN expression and suppressed cell proliferation, migration and invasion. Supplementary Figure 7: PTENP1 functions and regulation of PTEN are DICER dependent. Supplementary Figure 8: 5'AZA increased PTENP1 and PTEN expression and suppressed cell proliferation, migration and invasion. Supplementary Figure 9: Cisplatin and gemcitabine treatment increased PTENP1 expression.

SET domain-containing 2 (SETD2) is the most frequently mutated gene among all the histone methyltransferases in clear cell renal cell carcinoma (ccRCC). Microarrays, RNA sequencing analysis and exosomes analysis of cellular supernatant were performed after transfection A498 cells with si-SETD2 or siRNA of negative control. Chromatin immunoprecipitation and Luciferase reporter assay were conducted to evaluate the interaction between SETD2 and miR-10b. Functional and drug experiments in vitro and in vivo were performed to verify the role of SETD2, miR-10b and MAP4K4. The results showed that loss of SETD2 mediated downregulation of intracellular and exosomal microRNA-10b. MAP4K4 were relevant to oncogenesis of ccRCC caused by loss of SETD2 and miR-10b. SETD2 could directly target miR-10b and regulate the expression of multidrug resistance (MDR)-1 (P-gp170) through JNK pathway, which was one of the downstream pathways of MAP4K4. The coordinated expression of SETD2/H3K36me3/miR-10b/MAPKs/JNK/MDR pathway was revealed to the progression of ccRCC.

Supplementary Figure Legend

BackgroundInformation from the RENAL score is limited. This study aimed to identify new parameters based on three-dimensional (3D) reconstruction of preoperative enhanced computerized tomography (CT) for predicting outcomes after robot-assisted partial nephrectomy (RPN).Materials and methodsThe records of kidney cancer patients who underwent RPN at Tongji Hospital from March 2015 to July 2019 were reviewed. Demographic data, laboratory examinations, postoperative hospitalization time, and enhanced CT were retrospectively collected. Some tumor parameters were obtained from 3D reconstruction of CT data. The association between these predictive factors and outcomes after RPN was analyzed.ResultsA larger tumor bed area (TBA) was associated with a longer warm ischemia time (WIT) (P-value <0.001) and tumor resection time (P-value <0.001). Moreover, TBA was significantly associated with the elevation of postoperative creatinine (P-value = 0.005). TBA (P = 0.008), distance from the tumor to the first bifurcation of the renal artery (DTA) (P <0.034), and RENAL score (P = 0.005) were significantly associated with WIT in univariate logistic regression. In multivariate logistic regression, TBA (P = 0.026) and DTA (P = 0.048) were independent risk factors for prolonged WIT (over 25 min). The predictive effect of the combination of TBA, DTA, and RENAL score was higher than the predictive effect of RENAL score alone for WIT (area under curve: 0.786 versus 0.72).ConclusionTBA and DTA are independently associated with the WIT of RPN, which provides additional assessment value for the complexity of kidney cancer in RPN over the RENAL score.

Following the publication of the above article, an interested reader drew to the authors' attention that the 'NB‑4' and 'NB‑2' panels for the invasion and migration assays shown in Fig. 3B and C on p. 113 appeared to contain overlapping data, such that the data may have been derived from the same original source, even though the panels were intending to have shown results obtained under different experimental conditions. The authors have re‑examined their raw data and realized that these data were inadvertently mixed up when Fig. 3B and C were assembled. A corrected version of Fig. 3, showing the data as they should have appeared for the 'NB‑4' and 'NB‑2' invasion and migration assay experiments in Fig. 3B and C, is shown on the next page. The authors sincerely apologize for the errors that were introduced into Fig. 3 of the published article, and thank the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum. All the authors agree to the publication of the authors, and they apologize to the readership for any inconvenience caused. [Oncology Reports 29: 109‑116, 2013; DOI: 10.3892/or.2012.2069].

Objective:To explore the clinical characteristics, causes, diagnosis and treatment of transplant renal artery stenosis after pediatric-to-adult kidney transplantation.Methods:Between July 2014 and March 2019, clinical data were retrospectively reviewed for 25 en-bloc and 27 single kidney transplant cases.Results:One en-bloc(4.0%)and two single kidney recipients(7.4%)were diagnosed as renal artery stenosis at Month 13-23 months post-transplantation.It was higher than the rate of stenosis in adult-to-adult transplant cases(1.1%)during the same period.As compared with recipients without stenosis, stenotic ones had younger pediatric donors( P<0.05)and yet similar body weight of donors as well as recipients( P>0.05). The inner diameters of stenonotic sites were(1.40-1.63)mm and predominant stenotic site was proximal renal artery rather than anastomotic site.The remaining parts of major renal arteries varied from 2.31 to 4.93 mm in diameter.It was normal in children with a corresponding age.All three cases responded well to percutaneous transluminal angioplasty and stenting. Conclusions:The cause of stenosis may be an undeveloped local artery diameter due to extensive tissue dissection around artery.Therefore cautious selections of infantile single renal graft for adult recipients and preserving surrounding tissue of renal artery assist in the prevention of graft arterial stenosis.

Background:Previous researches have shown that the aberrant expression of Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in tumour tissues may serve as a biomarker for colorectal cancer (CRC) prognosis. However, these previous studies have small sample sizes and lacked validation from independent external populations. We therefore aimed to clarify the prognostic value of MALAT1 expression status in CRC patients using a large cohort and validate the findings with another large external cohort.Methods:The prognostic association between MALAT1 expression status and CRC outcomes was evaluated initially in a prospective cohort in China (n=164) and then validated in an external TCGA population (n=596). In the initial cohort, MALAT1 expression levels were quantified by quantitative reverse transcriptase polymerase chain reaction. Propensity score (PS) adjustment method was used to control potential confounding biases. The prognostic significance was reported as PS-adjusted hazard ratio (HR) and corresponding 95% confidence interval (CI).Results:There was no statistically significant association between MALAT1 expression status and CRC patient overall survival (OS) or disease free survival (DFS) in both initial cohort and external validation cohort populations. When combining these populations together, the results did not change materially. The summarized HRPS-adjusted were 1.010 (95% CI, 0.752-1.355, P=0.950) and 1.170 (95% CI, 0.910-1.502, P=0.220) for OS and DFS, respectively.Conclusions:MALAT1 expression status is not associated with prognostic outcomes of CRC patients. However, additional larger population studies are needed to further validate these findings.

Objective:To survey the public attitude towards xenotransplantation and examine its influencing factors.Methods:A survey form with 46 multiple-choice questions is offered. It is composed of general profiles of respondent and scale. The questionnaire is distributed online through the platform of Wenjuanxing(https: //). All adult respondents filled in anonymously online. Statistical processing included descriptive analysis, reliability and validity testing and variance and correlation analysis.Results:A total of 4 414 valid questionnaires are obtained between December 1, 2021 and January 31, 2022. Cronbach's alpha coefficient is 0.912 and the scale has decent reliability. Based upon the results of exploratory factor analysis, the items are grouped into five main factors, namely organ source, decision, psychosocial change, infection risk and other risks. If pig organs are proven feasible, the risks and prognosis are basically the same as human organs, 65.4% of the respondents definitely supported xenotransplantation. Among the respondents, individuals aged 31~50 years, male, born or resident in Chinese western region, higher education, non-medical institution practitioners, self/family members/friends have done or awaiting organ transplantation, self/partners supporting organ donation, future needs for organ transplantation, previous discussion of organ donation or organ transplantation with family/friends, blood donation, volunteer social worker, atheist or Buddhist/Christianc and hearing about xenotransplantation are more inclined to support xenotransplantation.Correlation analysis showed significant correlations among five main factors.Conclusions:Despite differences in attitudes towards xenotransplantation among different populations, overall attitude is favorable. Respondents are more concerned about their associated risks, especially psychosocial changes. The related researches should be stressed. And for different groups of people, corresponding stratified tutoring should be carried out. Strengthening clinical trials, heightening public attention and training medical staff are expected to further popularize this new technology.