Enhancing Efficacy and Safety in Laparoscopic Partial Nephrectomy for Localized Renal Tuberculosis: The Skirted Continuous Suture Technique.

BACKGROUND Limited research has been conducted on laparoscopic partial nephrectomy for kidney tuberculosis. This study aimed to evaluate the effectiveness of the skirted continuous suture technique in laparoscopic partial nephrectomy for localized renal tuberculosis. MATERIAL AND METHODS Five patients with kidney tuberculosis underwent standard retroperitoneal laparoscopic partial nephrectomy after computed tomography evaluation. The skirted continuous suture technique was utilized during the procedure. This retrospective study analyzed the outcomes of these patients who received treatment between January 2011 and December 2020 at Beijing Tsinghua Changgung Hospital and Eighth Medical Center of Chinese People's Liberation Army General Hospital. RESULTS The surgical success rate was 100%. Renal function was well preserved, with a decrease of glomerular filtration rate by 9.6±9.0 ml/min. Only 1 patient experienced postoperative urinous infiltration and lymphatic fistula, while the others did not have any surgical complications. Antituberculous therapy was continued postoperatively, and 1 patient had recurrence during follow-up. CONCLUSIONS The laparoscopic continuous suturing technique offers a reliable and straightforward method for extensively closing incision edges of the renal parenchyma in laparoscopic surgery. It contributes to the improved efficacy and safety of treating localized renal tuberculosis with exceptional application.

ATF4 renders human T-cell acute lymphoblastic leukemia cell resistance to FGFR1 inhibitors through amino acid metabolic reprogramming.

Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we explored whether FGFR1 acted a therapeutic target in human T-cell acute lymphoblastic leukemia (T-ALL) and the molecular mechanisms underlying T-ALL cell resistance to FGFR1 inhibitors. We showed that FGFR1 was significantly upregulated in human T-ALL and inversely correlated with the prognosis of patients. Knockdown of FGFR1 suppressed T-ALL growth and progression both in vitro and in vivo. However, the T-ALL cells were resistant to FGFR1 inhibitors AZD4547 and PD-166866 even though FGFR1 signaling was specifically inhibited in the early stage. Mechanistically, we found that FGFR1 inhibitors markedly increased the expression of ATF4, which was a major initiator for T-ALL resistance to FGFR1 inhibitors. We further revealed that FGFR1 inhibitors induced expression of ATF4 through enhancing chromatin accessibility combined with translational activation via the GCN2-eIF2α pathway. Subsequently, ATF4 remodeled the amino acid metabolism by stimulating the expression of multiple metabolic genes ASNS, ASS1, PHGDH and SLC1A5, maintaining the activation of mTORC1, which contributed to the drug resistance in T-ALL cells. Targeting FGFR1 and mTOR exhibited synergistically anti-leukemic efficacy. These results reveal that FGFR1 is a potential therapeutic target in human T-ALL, and ATF4-mediated amino acid metabolic reprogramming contributes to the FGFR1 inhibitor resistance. Synergistically inhibiting FGFR1 and mTOR can overcome this obstacle in T-ALL therapy.

Is the Supine Position Suitable for Ultrasound-Guided Percutaneous Nephrolithotomy in Patients with Complex Renal Stones?

INTRODUCTION: The aim of the study was to assess the safety and efficacy of ultrasound (US)-guided percutaneous nephrolithotomy (PCNL) for complex renal stones when performed in a modified supine position. METHODS: We retrospectively reviewed the charts of patients who underwent PCNL for complex renal stones at our institution between August 2018 and December 2021. During this time, 188 consecutive patients underwent US-guided PCNL in the prone position (P group, n = 129) or in the flank-free modified supine position (S group, n = 59). Patient demographics and intraoperative and postoperative data were analyzed. RESULTS: Successful renal access was achieved in all patients. The baseline demographics were comparable between the two groups. The numbers of renal access were significantly higher (2.1 ± 0.4 vs. 1.2 ± 0.2, p = 0.002), and the operation time was comparable (79.1 ± 14.6 min vs. 96.2 ± 19.6 min, p = 0.06) between the two groups. The postoperative hospital stay was also shorter in the P group (6.2 ± 1.5 d vs. 10.2 ± 1.7 d, p = 0.008). The postoperative hemoglobin loss was similar between the P and S groups (1.7 ± 0.4 g/dL vs. 1.8 ± 0.3 g/dL, p = 0.12). The stone-free rate was significantly lower in the S group (57.5% vs. 82.7%, p < 0.001). There were no embolization or septic complications. Twelve patients (20.3%) in the S group underwent simultaneous or staged retrograde flexible ureteroscopy to remove residual stones. CONCLUSION: US-guided PCNL in the modified supine position was a safe treatment for complex renal stones. However, the single-session stone clearance rate was not ideal. The supine flank-free position may be unsuitable for US-guided PCNL in patients with complex renal stones according to our preliminary findings.

Investigation of Immune Responses in Giant African Snail, Achatina immaculata, against a Two-Round Lipopolysaccharide Challenge.

As one of the 100 most-threatening invasive alien species, the giant African snail (Achatina immaculata) has successfully invaded and established itself in most areas of southern China. Protection against recurrent pathogen infections is vital to biological invasion. Enhanced immune protection has been previously found in other invertebrates, but not in the unique immune system of the giant African snail. In the present study, the survival rate of the giant African snail was recorded following a second infection with lethal doses of Escherichia coli after a previous first injection using lipopolysaccharide (LPS), and the mechanism of immune enhancement was investigated by examining the cellular and transcriptomic response of the giant African snail after two successive stimuli using LPS. Snails injected first with LPS, sterilized physiologic (0.9%) saline (SPS), phosphate-buffered saline (PBS) or untreated (Blank) were rechallenged at 7d with E. coli (Ec), and were named as LPS + Ec, SPS + Ec, PBS + Ec, Ec, and Blank. The log-rank test shows the survival rate of the LPS + Ec group as significantly higher than that of other control groups after the second injection (p < 0.05). By performing cell counting and BrdU labeling on newly generated circulating hemocytes, we found that the total hemocyte count (THC) and the ratio of BrdU-positive cells to total cells increased significantly after primary stimulation with LPS and that they further increased after the second challenge. Then, caspase-3 of apoptosis protease and two antioxidant enzyme activities (CAT and SOD) increased significantly after infection, and were significantly higher in the second response than they had been in the first round. Moreover, transcriptome analysis results showed that 84 differentially expressed genes (DEGs) were expressed at higher levels in both the resting and activating states after the second immune response compared to the levels observed after the first challenge. Among them, some DEGs, including Toll-like receptor 4 (TLR4) and its downstream signaling molecules, were verified using qRT-PCR and were consistent with the transcriptome assay results. Based on gene expression levels, we proposed that these genes related to the TLR signaling cascade participate in enhanced immune protection. All results provide evidence that enhanced immune protection exists in the giant African snail.

Outcomes of ultrasound-guided percutaneous nephrolithotomy for the treatment of large stones within non-functioning atrophic kidneys.

OBJECTIVES: To evaluate outcomes in patients who underwent total ultrasound-guided percutaneous nephrolithotomy for the management of large stones (>2 cm) within non-functioning atrophic kidneys, and to identify risk factors associated with postoperative persistence of urinary tract infection symptoms in such patients. METHODS: Between December 2014 and May 2019, 56 patients with large stones within non-functioning atrophic kidneys were treated at Beijing Tsinghua Changgung Hospital, Beijing, China, with total ultrasound-guided percutaneous nephrolithotomy. Factors including age, sex, previous medical history, stone burden, stone composition, stone-free rate, complication rate and postoperative urinary tract infection symptoms were retrospectively evaluated. Uni- and multivariate analyses were carried out to identify risk factors that predict persistence of urinary tract infection symptoms after percutaneous nephrolithotomy in such patients. RESULTS: The final stone-free rate after auxiliary treatments was 87.5%. The overall complication rate was 17.9%. After a median follow-up period of 12 months (range 6-40 months), three patients (5.4%) ultimately underwent nephrectomy. A total of 44 patients (78.6%) had no symptoms of urinary tract infection during follow up, whereas 63.6% of patients with diabetes continued to show persistent urinary tract infection symptoms at the latest follow up. Five patients (8.9%) showed improved total renal function, while most patients (83.9%) showed a stable estimated glomerular filtration rate. Diabetes was the only factor showing statistical significance in both univariate and multivariate analyses that predicted persistence of urinary tract infection symptoms after treatment with percutaneous nephrolithotomy. CONCLUSIONS: Ultrasound-guided percutaneous nephrolithotomy is a safe and feasible procedure that can be carried out in patients with large stones within non-functioning atrophic kidneys. However, for such patients with diabetes, percutaneous nephrolithotomy is not recommended.

Tract dilation monitored by ultrasound in percutaneous nephrolithotomy: feasible and safe.

PURPOSE: To investigate the feasibility and safety of tract dilation monitored by ultrasound in percutaneous nephrolithotomy (PCNL) and identify suitable patients for this technique. METHODS: Patients who underwent PCNL with only one access (24 Fr) using the balloon dilator or sequential dilators (Amplatz and telescopic metal dilators) from December 2014 to May 2018 in Beijing Tsinghua Changgung Hospital were retrospectively reviewed. Patients' demographic information, intra- and postoperative data were analyzed. Factors which would increase the success rate of ultrasound-guided balloon dilation were investigated by logistic regression analysis. RESULTS: There were 986 PCNLs performed. 207 cases underwent balloon dilation, while 411 underwent sequential dilation. The two groups did not significantly differ in age, sex, BMI, stone diameter, access location, operation time, postoperative complication rate, and stone-free rate. The balloon dilation group comprised 207 patients (115 males, 92 females) with a mean age of 51 ± 10 years. Mean BMI was 25.2 ± 3.3 kg/m2. Mean stone size was 3.6 ± 1.2 cm, 47.3% of which were staghorn stones. Hydronephrosis of the targeted calyx occurred in 78.3% of patients. Within the balloon dilation group, tract dilation failed in 24 cases (11.6%) on the first attempt. The successful and failed subgroups had comparable outcomes. Multivariate analysis revealed that the risk factors for the failure of access establishment were the presence of staghorn stones (p = 0.032), prior ipsilateral open nephrolithotomy (p = 0.026), and lower pole access (p = 0.039), while the success rate was significantly higher in those with a hydronephrotic target calyx (p = 0.001). CONCLUSIONS: Tract dilation using balloon catheter can be safely monitored by ultrasound, and is most suited to patients with a hydronephrotic target calyx.

Upper urinary tract stone compositions: the role of age and gender.

OBJECTIVE: To analyze the compositions of upper urinary tract stones and investigate their distributions in different gender and age groups. MATERIALS AND METHODS: Patients diagnosed with upper urinary tract stone disease between December 2014 and March 2018 were retrospectively reviewed. Patient's age, gender, BMI, comorbidities, stone event characteristics, and compositions were collected, and proportions of stone components in different gender and age groups were analyzed. RESULTS: A total of 1532 stone analyses were performed (992 from males and 540 from females). The mean age was younger in males (p<0.001). Males included more cases with larger BMI, hyperuricemia, and obesity, while females had more urinary tract infections. Multiple components were present in 61.8% of stones. Calcium oxalate (CaOx) (67.0%) was the most common component, followed by uric acid (UA) (11.8%), infection stone (11.4%), calcium phosphate (CaP) (8.0%), cystine (1.1%), brushite (0.4%), and 2,8-dihydroxyadenine (0.2%). Men contributed with more CaOx stones than women at age 30-49 years (all p<0.01) and more UA stones at 30-59 years (all p<0.05). Women contributed with more infection stones than men in age groups 30-49 and 60-69 years (all p<0.05), and more CaP stones at 30-49 years. The prevalence peak was 50-59 years in men and 60-69 years in women. Both genders had the lowest prevalence in adolescence. Prevalence of UA stones increased while that of infection stones decreased with aging in both genders. CONCLUSIONS: Age and sex had a strong association with distribution of stone compositions in this Chinese cohort.

Sirt3 modulate renal ischemia-reperfusion injury through enhancing mitochondrial fusion and activating the ERK-OPA1 signaling pathway.

Mitochondrial fusion is linked to heart and liver ischemia-reperfusion (IR) insult. Unfortunately, there is no report to elucidate the detailed influence of mitochondrial fusion in renal IR injury. This study principally investigated the mechanism by which mitochondrial fusion protected kidney against IR injury. Our results indicated that sirtuin 3 (Sirt3) was inhibited after renal IR injury in vivo and in vitro. Overexpression of Sirt3 improved kidney function, modulated oxidative injury, repressed inflammatory damage, and reduced tubular epithelial cell apoptosis. The molecular investigation found that Sirt3 overexpression attenuated IR-induced mitochondrial damage in renal tubular epithelial cells, as evidenced by decreased reactive oxygen species production, increased antioxidants sustained mitochondrial membrane potential, and inactivated mitochondria-initiated death signaling. In addition, our information also illuminated that Sirt3 maintained mitochondrial homeostasis against IR injury by enhancing optic atrophy 1 (OPA1)-triggered fusion of mitochondrion. Inhibition of OPA1-induced fusion repressed Sirt3 overexpression-induced kidney protection, leading to mitochondrial dysfunction. Further, our study illustrated that OPA1-induced fusion could be affected through ERK; inhibition of ERK abolished the regulatory impacts of Sirt3 on OPA1 expression and mitochondrial fusion, leading to mitochondrial damage and tubular epithelial cell apoptosis. Altogether, our results suggest that renal IR injury is closely associated with Sirt3 downregulation and mitochondrial fusion inhibition. Regaining Sirt3 and/or activating mitochondrial fission by modifying the ERK-OPA1 cascade may represent new therapeutic modalities for renal IR injury.

Alternol eliminates excessive ATP production by disturbing Krebs cycle in prostate cancer.

BACKGROUND: Alternol is a natural compound isolated from fermentation products of a mutant fungus. Our previous studies demonstrated that Alternol specifically kills cancer cells but spares benign cells. METHODS: To investigate the mechanism underlying alternol-induced cancer cell-specific killing effect, we took a comprehensive strategy to identify Alternol's protein targets in prostate cancer cells, including PC-3, C4-2, and 22RV1, plus benign BPH1 cell lines. Major experimental techniques included biotin-streptavidin pulldown assay coupled with mass-spectrometry, in vitro enzyme activity assay for Krebs cycle enzymes and gas chromatography-mass spectrometry (GC-MS) for metabolomic analysis. RESULTS: Among 14 verified protein targets, four were Krebs cycle enzymes, fumarate hydratase (FH), malate dehydrogenase-2 (MDH2), dihydrolipoamide acetyltransferase (DLAT) in pyruvate dehydrogenase complex (PDHC) and dihydrolipoamide S-succinyltransferase (DLST) in a-ketoglutarate dehydrogenase complex (KGDHC). Functional assays revealed that PDHC and KGDHC activities at the basal level were significantly higher in prostate cancer cells compared to benign prostate BPH1 cells, while alternol treatment reduced their activities in cancer cells close to the levels in BPH1 cells. Although FH and MDH2 activities were comparable among prostate cancer and benign cell lines at the basal level, Alternol treatment largely increased their activities in cancer cells. Metabolomic analysis revealed that Alternol treatment remarkably reduced the levels of malic acid, fumaric acid, and isocitric acid and mitochondrial respiration in prostate cancer cells. Alternol also drastically reduced mitochondrial respiration and ATP production in PC-3 cells in vitro or in xenograft tissues but not in BPH1 cells or host liver tissues. CONCLUSIONS: Alternol interacts with multiple Krebs cycle enzymes, resulting in reduced mitochondrial respiration and ATP production in prostate cancer cells and xenograft tissues, providing a novel therapeutic strategy for prostate cancer treatment.

Long-term outcomes of ultrasound-guided percutaneous nephrolithotomy in patients with solitary kidneys: a single-center experience.

PURPOSE: To report our experience with total ultrasound-guided percutaneous nephrolithotomy (PCNL) in the management of patients with solitary kidney, and evaluate the safety and feasibility of this technique. MATERIALS AND METHODS: Between October 2014 and December 2016, 48 patients with solitary kidneys underwent total ultrasound-guided PCNL at our institution. Stone-free rate (SFR), auxiliary procedures, and complications were recorded. Changes in renal function were evaluated by comparing preoperative and postoperative estimated glomerular filtration rates (eGFRs). Perioperative factors that may affect renal function were analyzed to define factors predicting renal function improvement on long-term follow-up. Of 48 patients, 44 were followed at least 6 months, whereas four patients were lost to follow-up. RESULTS: Among all patients, staghorn calculi were found in 18 (37.5%) patients. 14 (29.2%) patients required a two-stage PCNL. Struvite was found in six (12.5%) patients. Complications were reported in eight (16.7%) patients. Severe bleeding was noticed in three patients; no angioembolization was required. After a median follow-up of 12 (6-26) months, the final SFR was 81.8% after auxiliary treatments. There was a significant improvement of eGFR from 53.9 ± 24.0 to 61.3 ± 25.4 mL/min/1.73 m2 (P < 0.01). Renal function was stable, improved and worse in 65.9% (n = 29), 27.3% (n = 12), and 6.8% (n = 3) of patients, respectively, compared with preoperative levels. CONCLUSIONS: Ultrasound-guided PCNL is a safe and feasible procedure with an acceptably low complication rate in patients with solitary kidneys. At long-term follow-up, the renal function in more than 90% of the patients with solitary kidneys can be improved or stabilized after ultrasound-guided PCNL.

HEALER: homomorphic computation of ExAct Logistic rEgRession for secure rare disease variants analysis in GWAS.

MOTIVATION: Genome-wide association studies (GWAS) have been widely used in discovering the association between genotypes and phenotypes. Human genome data contain valuable but highly sensitive information. Unprotected disclosure of such information might put individual's privacy at risk. It is important to protect human genome data. Exact logistic regression is a bias-reduction method based on a penalized likelihood to discover rare variants that are associated with disease susceptibility. We propose the HEALER framework to facilitate secure rare variants analysis with a small sample size. RESULTS: We target at the algorithm design aiming at reducing the computational and storage costs to learn a homomorphic exact logistic regression model (i.e. evaluate P-values of coefficients), where the circuit depth is proportional to the logarithmic scale of data size. We evaluate the algorithm performance using rare Kawasaki Disease datasets. AVAILABILITY AND IMPLEMENTATION: Download HEALER at http://research.ucsd-dbmi.org/HEALER/ CONTACT: shw070@ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Simultaneous antegrade and retrograde endoscopic treatment of non-malignant ureterointestinal anastomotic strictures following urinary diversion.

BACKGROUND: The ureterointestinal anastomosis stricture (UAS) is a common complication of urinary diversion after radical cystectomy. For decades, open anastomotic revision remained the gold standard for the treatment of UAS. However, with the advancement in endoscopic technology, mini-invasive therapeutic approaches have been used in its management. Here, we report our experience with and long-term results of combined simultaneous antegrade and retrograde endoscopy (SARE) in the treatment of non-malignant UASs after urinary diversion in a consecutive series of patients. METHODS: From March 2012 to January 2015, there were 32 consecutive patients with 32 non-malignant UASs following radical cystectomy and urinary diversion. Twenty-nine patients were treated with SARE technique and comprised the study group. Using simultaneous antegrade flexible ureteroscope combined with retrograde semi-rigid ureteroscope or nephroscope, partial or complete strictures were managed with laser incision and balloon dilation under direct visualization. A 7/12 Fr graded endopyelotomy stent was left for 3-6 months after the procedure. Success was defined as symptomatic improvement and radiographic resolution of obstruction. RESULTS: With a median followup of 22 months (6-36), the overall success rate for SARE was 69.0%. Twenty patients with partial stricture had a success rate of 85%, and 9 patients with complete stricture had a success rate of 33.3%. Renal function, hydronephrosis grade, stricture type, and stricture length were significant influences on the outcome (P < 0.05). No complication was observed. CONCLUSIONS: The SARE is a safe and effective treatment for UAS, and may be the only endoscopic treatment approach for complete UAS. While success rate for complete strictures is low compared to open revision, it should be considered as an initial approach given its low overall morbidity. For partial strictures, prudent patient selection results in higher success rates that are nearly comparable to open revision.

Secure Multi-pArty Computation Grid LOgistic REgression (SMAC-GLORE).

BACKGROUND: In biomedical research, data sharing and information exchange are very important for improving quality of care, accelerating discovery, and promoting the meaningful secondary use of clinical data. A big concern in biomedical data sharing is the protection of patient privacy because inappropriate information leakage can put patient privacy at risk. METHODS: In this study, we deployed a grid logistic regression framework based on Secure Multi-party Computation (SMAC-GLORE). Unlike our previous work in GLORE, SMAC-GLORE protects not only patient-level data, but also all the intermediary information exchanged during the model-learning phase. RESULTS: The experimental results demonstrate the feasibility of secure distributed logistic regression across multiple institutions without sharing patient-level data. CONCLUSIONS: In this study, we developed a circuit-based SMAC-GLORE framework. The proposed framework provides a practical solution for secure distributed logistic regression model learning.

Privacy-preserving GWAS analysis on federated genomic datasets.

BACKGROUND: The biomedical community benefits from the increasing availability of genomic data to support meaningful scientific research, e.g., Genome-Wide Association Studies (GWAS). However, high quality GWAS usually requires a large amount of samples, which can grow beyond the capability of a single institution. Federated genomic data analysis holds the promise of enabling cross-institution collaboration for effective GWAS, but it raises concerns about patient privacy and medical information confidentiality (as data are being exchanged across institutional boundaries), which becomes an inhibiting factor for the practical use. METHODS: We present a privacy-preserving GWAS framework on federated genomic datasets. Our method is to layer the GWAS computations on top of secure multi-party computation (MPC) systems. This approach allows two parties in a distributed system to mutually perform secure GWAS computations, but without exposing their private data outside. RESULTS: We demonstrate our technique by implementing a framework for minor allele frequency counting and χ2 statistics calculation, one of typical computations used in GWAS. For efficient prototyping, we use a state-of-the-art MPC framework, i.e., Portable Circuit Format (PCF) 1. Our experimental results show promise in realizing both efficient and secure cross-institution GWAS computations.

Evaluation of laparoscopic vs robotic partial nephrectomy using the margin, ischemia and complications score system: a retrospective single center analysis.

OBJECTIVE: To evaluate differences between Laparoscopic Partial Nephrectomy (LPN) and Robot-Assisted Partial Nephrectomy (RAPN) using the Margin, Ischemia and Complications (MIC) score system and to evaluate factors related with MIC success. MATERIALS AND METHODS: Single centre retrospective study on 258 LPN and 58 RAPN performed between January 2012 and January 2014. Success was defined when surgical margins was negative, Warm Ischemia Time (WIT) was ≤ 20 minutes and no major complications occurred. Mann-Whitney-U and Pearson χ2 correlation were used to compare LPN and RAPN. A matched pair comparison was also performed. Spearman correlation (Rho) was used to evaluate the relationship between clinical, intra and post-operative and pathological patients characteristics with MIC score. A binary regression analysis was also performed to evaluate independent factors associated with MIC success. RESULTS: The MIC rate in LPN and RAPN was 55% and 65.5% respectively. No differences in clinical, intra and post-operative outcomes between groups were found. Clinical tumor size (p-value: < 0.001; OR: 0.829; 95% CI: 0.697-0.987), PADUA score (p-value: < 0.001; OR: 0.843; 95% CI: 0.740-0.960), PADUA risk groups (intermediate; p-value: < 0.001; OR: 0.416; 95% CI: 0.238- 0.792; high: p-value: < 0.001; OR: 0.356; 95% CI: 0.199- 0.636), WIT (p-value: < 0.001; OR: 0.598; 95% CI: 0.530- 0.675) were independently associated with MIC. eGFR (< 60 vs ≥ 60 ml/min per 1.73 m2: p-value: < 0.001; OR: 3.356; 95% CI: 1.701-6.621) and Fuhrman nuclear grade (p-value: 0.014; OR: 1.798; 95% CI:1.129-2.865) were also independently associated with MIC. CONCLUSIONS: MIC score system is a simple and useful tool to report and to compare different surgical approach.

ZIF-derived sulfides with tremella-like core-shell structure for high performance supercapacitors.

Metal-organic frameworks (MOFs) have emerged as promising active electrode materials in supercapacitors for its controllable porous structure and excellent physio-chemical properties. However, the poor conductivities keep it from achieving its full capacitance potential, which greatly limits its practical application. Here, a facile pathway is reported to fabricate the GO/Ni2ZnS4@NiCo2S4 composite with large specific surface area and favorable electrical conductivity. Thanks to the novel tremella-like core-shell structure and high-efficient synergistic effects among multi-components, the designed GO/Ni2ZnS4@NiCo2S4 electrode shows a high specific capacitance of 2284 F/g at 1 A/g. Furthermore, the asymmetric supercapacitor fabricated by coupling GO/Ni2ZnS4@NiCo2S4 positive electrode with biological carbon negative electrode achieves a remarkable energy density of 120 Wh kg-1 at a power density of 750 W kg-1.

High and selective cytotoxicity of ex vivo expanded allogeneic human natural killer cells from peripheral blood against bladder cancer: implications for natural killer cell instillation after transurethral resection of bladder tumor.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is treated with transurethral resection of bladder tumor (TURBT) followed by intravesical instillation of chemotherapy or Bacillus Calmette-Guérin therapy. However, these treatments have a high recurrence rate and side effects, emphasizing the need for alternative instillations. Previously, we revealed that expanded allogeneic human natural killer (NK) cells from peripheral blood are a promising cellular therapy for prostate cancer. However, whether NK cells exhibit a similar killing effect in bladder cancer (BCa) remains unknown. METHODS: Expansion, activation, and cryopreservation of allogeneic human NK cells obtained from peripheral blood were performed as we previously described. In vitro cytotoxicity was evaluated using the cell counting kit-8. The levels of perforin, granzyme B, interferon-γ, tumor necrosis factor-α, and chemokines (C-C-motif ligand [CCL]1, CCL2, CCL20, CCL3L1, and CCL4; C-X-C-motif ligand [CXCL]1, CXCL16, CXCL2, CXCL3, and CXCL8; and X-motif ligand 1 and 2) were determined using enzyme-linked immunosorbent assay. The expression of CD107a, major histocompatibility complex class I (MHC-I), MHC-I polypeptide-related sequences A and B (MICA/B), cytomegalovirus UL16-binding protein-2/5/6 (ULBP-2/5/6), B7-H6, CD56, CD69, CD25, killer cell Ig-like receptors (KIR)2DL1, KIRD3DL1, NKG2D, NKp30, NKp46, and CD16 of NK cells or BCa and normal urothelial cells were detected using flow cytometry. Cytotoxicity was evaluated using lactate dehydrogenase assay in patient-derived organoid models. BCa growth was monitored in vivo using calipers in male NOD-scid IL2rg-/- mice subcutaneously injected with 5637 and NK cells. Differential gene expressions were investigated using RNA sequence analysis. The chemotaxis of T cells was evaluated using transwell migration assays. RESULTS: We revealed that the NK cells possess higher cytotoxicity against BCa lines with more production of cytokines than normal urothelial cells counterparts in vitro, demonstrated by upregulation of degranulation marker CD107a and increased interferon-γ secretion, by MICA/B/NKG2D and B7H6/NKp30-mediated activation. Furthermore, NK cells demonstrated antitumor effects against BCa in patient-derived organoids and BCa xenograft mouse models. NK cells secreted chemokines, including CCL1/2/20, to induce T-cell chemotaxis when encountering BCa cells. CONCLUSIONS: The expanded NK cells exhibit potent cytotoxicity against BCa cells, with few toxic side effects on normal urothelial cells. In addition, NK cells recruit T cells by secreting a panel of chemokines, which supports the translational application of NK cell intravesical instillation after TURBT from bench to bedside for NMIBC treatment.

Analysis of risk factors for positive surgical margin after laparoscopic radical prostatectomy with and without neoadjuvant hormonal therapy.

Background: Positive surgical margins (PSM) is not only an independent risk factor for recurrence, metastasis, and prognosis, but also an important indicator of adjuvant therapy for prostate cancer (PCa) patients treated with radical prostatectomy (RP). At present, there are few reports analyzing risk factors of PSM in laparoscopic RP (LRP), especially for those PCa cases who accepted neoadjuvant hormonal therapy (NHT). Hence, the aim of the current study was to explore risk factors for PSM after LRP in PCa patients with and without NHT. Methods: The clinicopathological data of patients who underwent LRP from January 2012 to July 2020 was retrospectively analyzed. Risk factors for PSM after LRP in NHT and non-NHT groups were respectively explored. Results: The overall PSM rate was 33.3% (90/270), PSM rate was 39.3% (64/163) in patients without NHT and 24.3% (26/107) in those with NHT. The apex was the most common location of PSM in non-NHT group (68.8%, 44/64), while the fundus was the most common location of PSM in NHT group (57.7%, 15/26). Multiple logistic regression revealed that body mass index (BMI), PSA, ISUP grade after LRP, pathological stage T (pT) and pathological lymph node status (pN) were independent factors affecting the PSM for patients without NHT (OR=1.160, 95%CI:1.034-1.301, p=0.011; OR=3.385, 95%CI:1.386-8.268, p=0.007; OR=3.541, 95%CI:1.008-12.444, p=0.049; OR=4.577, 95%CI:2.163-9.686, p<0.001; OR=3.572, 95%CI:1.124-11.347, p=0.031), while pT, pN, and lymphovascular invasion (LVI) were independent risk factors affecting PSM for patients with NHT (OR=18.434, 95%CI:4.976-68.297, p<0.001; OR=7.181, 95%CI:2.089-24.689, p=0.002; OR=3.545, 95%CI:1.109-11.327, p=0.033). Conclusions: The apex was the most common location in NHT group, and BMI, PSA, ISUP after LRP, pT and pN were independent risk factors affecting PSM for NHT patients; while the fundus was the most common location in non-NHT group, and pT, pN, and LVI were independent risk factors affecting PSM for non-NHT patients.

The association of marital status with kidney cancer surgery morbidity - a retrospective cohort study.

Purpose: To better understand whether the marital status impacts 90-day postoperative outcomes following kidney cancer surgery. Methods: We performed a retrospective cohort study of adult patients undergoing elective partial or radical nephrectomy to manage kidney masses from 2003 to 2017 using the Premier Hospital Database, a national hospital discharge dataset. Multinomial logistic regression models controlling for a wide range of clinicodemographic, surgical, and hospital characteristics were used to assess an association between marital status and postoperative complications. The primary outcome was 90-day complications, including minor complications (Clavien grades 1-2), non-fatal major complications (Clavien grades 3-4), and mortality (Clavien grade 5). Secondary outcomes included patient disposition and readmission rates. Results: The study cohort comprised 106,752 patients, of which 61,188 (57.32%) were married. The overall incidence of minor complications, major complications, and death was 24.04%, 6.00%, and 0.71%, respectively. Marriage was associated with a significantly lower incidence of minor (RR 0.97; 95% CI: 0.94-0.99) complications following open or radical nephrectomy and major complications (RR 0.89; 95% CI: 0.84-0.95) for all surgical types and approaches. There was no association between marital status and mortality (RR 0.94; 95% CI: 0.81-1.10). Conclusion: Marriage is associated with a significant reduction in major complications following kidney cancer surgery, likely because it is associated with greater social support, which is beneficial in the postoperative phase of care. Marital status and social support may play a role in the preoperative decision-making process and counseling for patients considering kidney cancer surgery.

Smoking status among cancer patients by specialty: A U.S. nationwide representative analysis.

BACKGROUND: Persistence in tobacco use among cancer survivors has been associated with a multitude of clinicodemographic factors. However, there is a paucity of understanding regarding the role the healthcare professional's specialty plays in tobacco cessation in tobacco-related cancer survivors. METHODS: We conducted a cross-sectional analysis of data from cancer survivors with a smoking history using the Behavioral Risk Factor Surveillance System (BRFSS) database to examine differences in the proportion of patients continuing tobacco use among patients with a diagnosis of cancer segregated by cancer site specialty over the 2016-2020 period. We accounted for complex survey design and used sampling weights to obtain a nationwide representative sample. We employed modified Poisson regression adjusting for age, gender, education, income, race, marital status, and medical specialty. RESULTS: We analyzed 19,855 cancer survivors with a current or past history of tobacco use, of whom 5222 (26,3%) self-reported to be current smokers. Patients with urological and gynecological tobacco-related malignancies had a higher relative risk (RR) of being current smokers with a RR of 1.30 (95% confidence interval, 1.12-1.51) and 1.25 (95% confidence interval, 1.12-1.39) respectively. Malignant Hematology had the lowest RR of smoking status among all other specialties RR 0.85 (95% confidence interval, 0.59-1.21). CONCLUSIONS: Continuing smoking rates among tobacco-related cancer survivors were different between specialties. One in four cancer survivors were current smokers; this emphasizes health professionals' paramount role in tobacco cessation counseling.