Objective: To explore the safety and feasibility of the disconnection of the left renal artery preferentially during robot-assisted inferior vena cava (IVC) thrombectomy for patients with left renal cell carcinoma and tumor emboli. Methods: Clinical data of 7 patients who underwent robot-assisted IVC thrombectomy and radical nephrectomy in the First Affiliated Hospital of Zhengzhou University during Dec.2021 and Oct.2024 were retrospectively analyzed.Thrombectomy was performed first，followed by nephrectomy. The “IVC-first, kidney-last”robotic technique was developed to minimize chances of IVC thrombus. When patients in left lateral decubitus position, the left renal artery was severed from the right side through the inferior vena cava and abdominal aorta. After removal of thrombus from IVC was completed, patients changed to the right lateral position to complete radical left nephrectomy. Results: Imaging examinations revealed that the median diameter of the renal cell carcinomas was 83(46-99) mm; the median length of the inferior vena cava cancerous emboli was 49(2-91) mm.According to the Mayo classification，the cancerous emboli were gradeⅠ in 2 cases，gradeⅡ in 4 cases，and grade Ⅲ in 1 case.All surgeries were successful.The median operation time was 248(201-331) minutes，blood loss 500(200-1000) mL，and 6 cases required intraoperative blood transfusion.The median time for transition into the intensive care unit was 1(1-4) days，and drainage tube removal 6(5-12) days.Serum creatinine increased significantly in 5 cases，4 of which returned to normal after 1 week，but 1 had renal insufficiency (creatinine 166 μmol/L).Chylous fistula occurred in 1 patient，and lower extremity venous thrombosis developed in 3 patients.Pathological examinations indicated 6 cases of renal cell carcinoma and 1 case of MiT family translocation renal cell carcinoma.During the median follow-up of 17(1-35) months，5 cases were tumor-free，while 2 had lung and retroperitoneal metastases.They received targeted therapy of axitinib combined immunotheraphy and lived with tumors. Conclusion: In the left lateral position for left renal cell carcinoma with cancerous emboli，robot-assisted laparoscopic thrombectomy by crossing the inferior vena cava and abdominal aorta and disconnecting the left renal artery first is safe and feasible.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Chronic sinusitis with nasal polyps(CRSwNP)is a highly heterogeneous chronic inflammatory disease,that persistently impacts patients'quality of life.To date,its etiology and pathogenesis remain incompletely unclear.Animal models serve as crucial tools for exploration of CRSwNP pathogenesis However,there is still a lack of a recognized mature and stable mouse model of CRSwNP in basic research.The stable mouse model of CRSwNP has become a key bottleneck in the analysis of the pathogenesis.This paper systematically reviews existing construction methodologies,inflammatory phenotypes,and applicability of murine CRSwNP models.By comparing their advantages and limitations,we will explore future optimization directions.This review will provide a theoretical basis and foundation for the basic research and clinical precision treatment of CRSwNP.

Objective To compare the clinical efficacy and postoperative urinary control between robot-assisted radical prostatectomy(RARP)with posterior-anterior-lateral(PAL)approach and with anterior(conventional)approach using propensity score matching method.Methods Clinical data of 145 patients undergoing RARP in our hospital during Jan.2020 and Jan.2023 were retrospectively analyzed,including 122 patients in the conventional group and 23 in the PAL group.The patients were matched by 2∶1 propensity score matching,including 46 cases in the conventional group and 23 in the PAL group.The perioperative outcomes were compared of prostate cancer(PCa)patients undergoing RARP surgery with different approaches before and after matching,including operation time,intraoperative blood loss,pelvic drainage time,hospitalization days,preservation of neurovascular bundles(NVB)during surgery,deep dorsal venous complex(DVC)suture,reconstruction of bladder neck,and postoperative urinary control recovery rate after extubation immediately,and 1,3,and 6 months after surgery.Results There were no significant differences in baseline data,operation time,bleeding volume,pelvic drainage time,hospitalization days,preservation of NVB,and reconstruction of bladder neck between the two groups(P＞0.05).The PAL group used less DVC suture during surgery(30.4％vs.100％,P＜0.001),but had better urinary control recovery rate immediately after extubation,1,3 and 6 months after surgery(P＜0.05).Conclusion RARP with PAL approach is as safe and effective as the conventional approach,and has significant advantages in early postoperative urinary control.

OBJECTIVE To investigate the potential therapeutic effect of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" from the perspective of immunomodulation and cardioprotection. METHODS Chemical components of the sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" were analyzed by UPLC-Q-TOF-MS and colorimetric methods. Examined tablet’s effects on zebrafish models of macrophage reduction, heart failure, H2O2-induced oxidative stress in myocardial and endothelial cells, and a microglial inflammation model induced by lipopolysaccharide. Immune regulation and cardioprotective effects were evaluated through multiple indicators, including macrophage formation and phagocytosis abilities, anti-neuroinflammation ability, cardiac systolic and diastolic functions, and anti-oxidative stress injury ability in myocardial and endothelial cells. RESULTS The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" improved macrophage formation and phagocytosis, cardiac systolic and diastolic functions, reduced neuroinflammation, and alleviated oxidative stress in myocardial and endothelial cells, resulting in immunomodulatory and cardioprotective effects. CONCLUSION The sporoderm-removed Ganoderma lucidum spore tablet "Xianzhi No.3" maybe a potential therapeutic agent for regulating the immune system and protecting cardiac function.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by numerous chromosomal number and structural abnormalities, which are of great significance for risk stratification and response evaluation of MM patients. Optical genome mapping (OGM) is a novel technology that has the potential to resolve many of the issues and limitations associated with traditional cytogenetic methods. To date, the clinical utility of OGM has been validated in the fields of cancer, reproduction, and embryonic dysplasia, et al. In this study, we compared OGM to traditional techniques for the first time in five newly diagnosed MM patients, and evaluated the potential of OGM for detecting cytogenetic aberrations and its clinical application value in MM.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo. Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.

ObjectiveTo evaluate the effectiveness and consistency of three commonly used early colorectal cancer screening models for advanced colorectal adenoma as a noninvasive means， and to assess the predictive value of traditional Chinese medicine （TCM） tongue images in the models. MethodsPatients diagnosed with colorectal adenoma who underwent colonoscopy and pathological examination were selected as the study participants. Basic clinical data and tongue image were collected. The prediction models of Asia-Pacific colorectal screening （APCS） model， its revision （M-APCS） and colorectal neoplasia predict （CNP） model were applied to compare the predictive effects of the three models on advanced stage adenomas of the colon， the differences in clinical data and traditional Chinese medicine tongue characteristics among patients with different degrees of adenomas， and the similarities and differences in tongue characteristics among the models. The discriminative ability of the three risk models was evaluated using the area under the curve （AUC） and receiver operating characteristic （ROC） curves. The calibration was assessed using the Kuder-Richardson coefficient and the Hosmer-Lemeshow test for consistency analysis. ResultsA total of 227 patients with adenoma were analyzed， including 104 patients （45.82%） with advanced adenoma. In the detection of advanced adenoma， those with greasy coating （70 cases， 67.3%） were higher than those without greasy coating （34 cases， 32.7%， P＜0.05）. After multivariate analysis， the odds ratio （OR） value of non-greasy coating was 0.371 （0.204~0.673， P＜0.01）， indicating that non-greasy coating was a protective factor for advanced adenomas. Among the three risk models， the detection rate of advanced adenoma in the high-risk group with APCS was the highest （63.3%）， which was 1.49 times and 2.04 times that of the medium-risk group （42.6%） and the low-risk group （31.1%， P＜0.01）. The detection rate of advanced adenomas in high-risk groups of M-APCS and CNP was slightly higher than that in moderate or low risk groups （P＞0.05）. The proportion of yellow and greasy coating in high-risk group was higher than that in the medium-risk or low-risk group （P＜0.05）. For the ability to distinguish advanced and non-advanced adenomas， the AUC of APCS was 0.629 （95% CI： 0.556~0.702） and was higher than that of M-APCS （0.591） and CNP （0.586）. In calibration evaluation， Cronbach's alpha was 0.919 （＞0.7）， which indicated that the three models were consistent. In the correlation matrix， the correlation coefficients between APCS model and M-APCS model， and CNP model were 0.794 and 0.717， respectively， and the correlation coefficients between M-APCS model and CNP model were 0.873， Hosmer-Lemeshow χ² =2.552， P＞0.05， which suggested that the three models had good calibration ability. ConclusionAll three models demonstrate the efficiency to identify advanced colorectal adenoma， and their calibration ability is considered to be good. Among the three models， the APCS exhibits the highest recognition efficiency， however， the recognition accuracy of the APCS model needs improvement. The presence of a greasy coating is identified as one of the potential predictors of advanced adenoma. Consequently， it can be considered for inclusion in the risk model of advanced colorectal adenoma to enhance the accuracy.