Comprehensive treatment of von Hippel-Lindau disease: A case report.

von Hippel-Lindau (VHL) disease is a rare autosomal dominant multiorgan disease characterized by several benign and malignant tumors rich in vascular, as well as cysts in other organs. A great clinical treatment strategy is significantly warranted for good prognosis of patients with VHL disease. Herein, we reported a case of a 45-year-old woman diagnosed with VHL disease with spinal hemangioblastoma (HB) and clear cell renal cell carcinoma (ccRCC). Four years after the resection of the right kidney, a recurrent RCC in the right kidney and a malignant lesion in the left kidney were observed. This patient was started on sorafenib (800 mg, daily) and tislelizumab (200 mg per 3 weeks). After 6 months of treatment, the size of renal cell carcinoma was dramatically reduced and renal function improved. More importantly, she achieved partial response during the whole treatment. Microscopically, intramedullary masses resection was done and the HB in T4-5 thoracic spinal was removed. Neurologic symptoms such as numbness and pain were remarkably alleviated. Additionally, tislelizumab-induced elevation in liver transaminase levels and hypothyroidism were revered by hepatoprotector and levothyroxine, respectively. In short, comprehensive treatment strategies may benefit patients with VHL disease, especially with HB and ccRCC.

Concentration controlling of carboxylic ester-based electrolyte for low temperature lithium-ion batteries.

Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li+ ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments.

A multi-classifier system integrated by clinico-histology-genomic analysis for predicting recurrence of papillary renal cell carcinoma.

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

[Robot-assisted laparoscopic ureteroplasty with buccal mucosa graft for complex ureteral stricture].

OBJECTIVE: To investigate the feasibility, safety and effectiveness of robot-assisted laparoscopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture. METHODS: The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted laparoscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology, Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed. Intraoperative conditions, postoperative complications and follow-up data were also recorded and analyzed. RESULTS: The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery. The study included 14 males and 6 females with a mean age of (41±11) years (range: 19 to 60 years) and a mean body mass index of (24.3±3.6) kg/m2 (range: 18.2 to 31.8 kg/m2). There were 9 cases on the left side and 11 cases on the right side. The strictures of all the patients were located in the proximal segment of the ureter (including the ureteropelvic junction). The mean preoperative serum creatinine was (92.2±23.3) µmol/L (range: 49.2 to 138.9 µmol/L), and the mean length of ureteral stricture was (2.8±0.9) cm (range: 1.0 to 4.0 cm). Ten patients had previously undergone unsuccessful reconstructive surgery. During the operation, 12 patients received posteriorly augmented anastomosis with ventral onlay. The mean length of the buccal mucosa graft harvested during the operation was (3.1±0.6) cm (range: 2.0 to 4.3 cm), and the median width was 1.5 cm (range: 1.0 to 2.0 cm). The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases. The median operative time was 154 min (range: 113 to 300 min), and the median estimated blood loss was 45 mL (range: 0 to 100 mL). The median postoperative hospital stay was 4 d (range: 4 to 14 d). The mean postoperative follow-up time was (15.0±1.7) months (range: 12.5 to 17.9 months), and the surgical success rate was 100.0% in this study. After surgery, 11 patients reported mild discomfort at the oral donor site, 2 patients deve-loped urinary tract infection, and no postoperative complications were reported in the other 7 patients. The mean serum creatinine was (90.9±23.9) µmol/L (range: 60.0 to 153.0 µmol/L) six months after surgery. CONCLUSION: Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications, which has shown good feasibility, safety and effectiveness. However, large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.

Renal function after ureteral reconstruction surgery in patients with solitary kidney.

Background: Ureteral strictures (US) could lead to impaired kidney function, which was alleviated by ureteral reconstruction surgery. However, solitary kidney (SK) patients with US were more complicated to treat. This study aimed to evaluate the impact of reconstruction surgery on renal function based on estimated glomerular filtration rate (eGFR) in patients with SK. Methods: We retrospectively enrolled patients who underwent reconstruction surgery between April 2014 to March 2022. eGFR was measured pre- and postoperatively. The 'static renal function' was defined as a change in eGFR of 20% or less at the last follow-up, and the 'worsening renal function group' was defined as a decrease of greater than 20%. Results: A total of 61 SK patients were involved. The success rate of ureteral reconstruction surgery was 90.16% (55/61). The median follow-up time was 20.8 months (range, 3.7-109.2 months). The median eGFR was 65.5 (range, 15.1-99.9) and 65.3 (range, 3.8-123.4) mL/min/1.73 m2 at the baseline and the last follow-up. No statistically significant difference in eGFR was observed between the preoperative baseline and last follow-up visits (P=0.58). However, in patients with baseline renal dysfunction [chronic kidney disease (CKD) stage 3-5], the eGFR significantly improved at the last follow-up compared to the baseline (P=0.02). Three patients developed a 'worsening renal function' (4.92%). Besides, the systolic blood pressures (SBP) at follow-up significantly reduced compared to the preoperative baseline (P=0.002). Conclusions: Ureteral reconstruction surgery is an effective treatment to preserve renal function, which also achieves a high success rate and is associated with the reduction of SBP for SK patients with US.

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT.

Endothelial-to-mesenchymal transition (EndMT) is a key driver of atherosclerosis. Aerobic glycolysis is increased in the endothelium of atheroprone areas, accompanied by elevated lactate levels. Histone lactylation, mediated by lactate, can regulate gene expression and participate in disease regulation. However, whether histone lactylation is involved in atherosclerosis remains unknown. Here, we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactate-dependent histone H3 lysine 18 lactylation (H3K18la) in vitro and in vivo, as well as in atherosclerotic patients' arteries. Mechanistically, the histone chaperone ASF1A was first identified as a cofactor of P300, which precisely regulated the enrichment of H3K18la at the promoter of SNAI1, thereby activating SNAI1 transcription and promoting EndMT. We found that deletion of ASF1A inhibited EndMT and improved endothelial dysfunction. Functional analysis based on Apoe KO Asf1a ECKO mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endothelium-specific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis development. Inhibition of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la, SNAI1 transcription, and EndMT-induced atherosclerosis. This study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis, which provides emerging therapies for atherosclerosis.

Heritability of functional gradients in the human subcortico-cortical connectivity.

The human subcortex plays a pivotal role in cognition and is widely implicated in the pathophysiology of many psychiatric disorders. However, the heritability of functional gradients based on subcortico-cortical functional connectivity remains elusive. Here, leveraging twin functional MRI (fMRI) data from both the Human Connectome Project (n = 1023) and the Adolescent Brain Cognitive Development study (n = 936) datasets, we construct large-scale subcortical functional gradients and delineate an increased principal functional gradient pattern from unimodal sensory/motor networks to transmodal association networks. We observed that this principal functional gradient is heritable, and the strength of heritability exhibits a heterogeneous pattern along a hierarchical unimodal-transmodal axis in subcortex for both young adults and children. Furthermore, employing a machine learning framework, we show that this heterogeneous pattern of the principal functional gradient in subcortex can accurately discern the relationship between monozygotic twin pairs and dizygotic twin pairs with an accuracy of 76.2% (P < 0.001). The heritability of functional gradients is associated with the anatomical myelin proxied by MRI-derived T1-weighted/T2-weighted (T1w/T2w) ratio mapping in subcortex. This study provides new insights into the biological basis of subcortical functional hierarchy by revealing the structural and genetic properties of the subcortical functional gradients.

Whole-exome sequencing of individuals from an isolated population under extreme conditions implicates rare risk variants of schizophrenia.

Schizophrenia (SCZ), which affects approximately 1% of the world's population, is a global public health concern. It is generally considered that the interplay between genes and the environment is important in the onset and/or development of SCZ. Although several whole-exome sequencing studies have revealed rare risk variants of SCZ, no rare coding variants have been strongly replicated. Assessing isolated populations under extreme conditions might lead to the discovery of variants with a recent origin, which are more likely to have a higher frequency than chance to reflect gene-environment interactions. Following this approach, we examined a unique cohort of Tibetans living at an average altitude above 4500 meters. Whole-exome sequencing of 47 SCZ cases and 53 controls revealed 275 potential novel risk variants and two known variants (12:46244485: A/G and 22:18905934: A/G) associated with SCZ that were found in existing databases. Only one gene (C5orf42) in the gene-based statistics surpassed the exome-wide significance in the cohort. Metascape enrichment analysis suggested that novel risk genes were strongly enriched in pathways relevant to hypoxia, neurodevelopment, and neurotransmission. Additionally, 47 new risk genes were followed up in Han sample of 279 patients with SCZ and 95 controls, only BAI2 variant appearing in one case. Our findings suggest that SCZ patients living at high altitudes may have a unique risk gene signature, which may provide additional information on the underlying biology of SCZ, which can be exploited to identify individuals at greater risk of exposure to hypoxia.

BSA-stabilized selenium nanoparticles ameliorate intracerebral hemorrhage's-like pathology by inhibiting ferroptosis-mediated neurotoxicology via Nrf2/GPX4 axis activation.

Intracerebral hemorrhage (ICH) is a prevalent hemorrhagic cerebrovascular emergency. Alleviating neurological damage in the early stages of ICH is critical for enhancing patient prognosis and survival rate. A novel form of cell death called ferroptosis is intimately linked to hemorrhage-induced brain tissue injury. Although studies have demonstrated the significant preventive impact of bovine serum albumin-stabilized selenium nanoparticles (BSA-SeNPs) against disorders connected to the neurological system, the neuroprotective effect on the hemorrhage stroke and the mechanism remain unknown. Therefore, based on the favorable biocompatibility of BSA-SeNPs, h-ICH (hippocampus-intracerebral hemorrhage) model was constructed to perform BSA-SeNPs therapy. As expected, these BSA-SeNPs could effectively improve the cognitive deficits and ameliorate the damage of hippocampal neuron. Furthermore, BSA-SeNPs reverse the morphology of mitochondria and enhanced the mitochondrial function, evidenced by mitochondrial respiration function (OCR) and mitochondrial membrane potential (MMP). Mechanistically, BSA-SeNPs could efficiently activate the Nrf2 to enhance the expression of antioxidant GPX4 at mRNA and protein levels, and further inhibit lipid peroxidation production in erastin-induced ferroptotic damages. Taken together, this study not only sheds light on the clinical application of BSA-SeNPs, but also provides its newly theoretical support for the strategy of the intervention and treatment of neurological impairment following ICH.

Minimally invasive versus open ileal ureter with ileocystoplasty: comparative outcomes and 5-year experience.

PURPOSE: To present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures. PATIENTS AND METHODS: From December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared. RESULTS: The etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC. CONCLUSION: IUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.

Successful management of a multiple endocrine neoplasia type 1-associated thymic neuroendocrine neoplasms with acute chest pain as initial symptom: A rare case report.

Key Clinical Message: Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1-associated NEN. Abstract: Multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor MEN1 gene. Patients with MEN1-associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45-year-old man who developed MEN1-associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of MEN1 gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67-positive cells (2%) in MEN1-associated NEN. Further evaluation unveiled MEN1-associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc-HYNIC-TOC scintigraphy showed that focally increased radioactivity in the mid-upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.

Prognostic value of tumor-stroma ratio in clear cell renal cell carcinoma after surgery.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common urological tumors, and its incidence is increasing year by year. Tumor stroma ratio (TSR) can reflect the amount of stromal component around tumor cells, and can independently predict the prognosis of tumor. This study aims to evaluate the prognostic value of TSR in ccRCC patients. Methods: From January 2010 to December 2015, clinical and histopathological data of patients with ccRCC patients who underwent surgical operation were collected. Using TSR (50%) as the cut-off value, the patients were divided into low-TSR group (<50%) and high-TSR group (≥50%). The clinicopathological characteristics and survival status of patients were compared between the two groups. Univariate and multivariate analyses were used to identify the prognostic factors for overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS). Results: The mean age of 569 patients was 56.84±12.76 years old. There were 401 males and 168 females. According to the TSR, patients were divided into low-TSR group (n=333, 58.5%) and high-TSR group (n=236, 41.5%). The median follow-up time was 67.0 months (interquartile range, 33.0-72.0 months). The 5-year OS, CSS and MFS were 91.2%, 94.6% and 91.0%, respectively. The 5-year OS, CSS and MFS were 84.2%,89.7% and 82.7% in the high-TSR group and 96.1%, 98.0% and 96.0% in the low-TSR group (P<0.05). Multivariate analysis showed that age >60 years [hazard ratio (HR) =2.455, 95% confidence interval (CI): 1.292-4.668, P=0.006), tumor grade (HR =6.580, 95% CI: 3.276-13.216, P<0.001) and TSR (HR =2.611, 95% CI: 1.265-5.387, P=0.009) were independent prognostic factors for OS. Multivariate analysis showed that tumor stage (HR =3.213, 95% CI: 1.437-7.184, P=0.004), tumor grade (HR =6.102, 95% CI: 2.664-13.976, P<0.001) and TSR (HR =2.653, 95% CI: 1.063-6.621, P=0.03) were independent prognostic factors for CSS. Multivariate analysis showed that tumor stage (HR =4.805, 95% CI: 2.677-8.624, P<0.001), tumor grade (HR =6.423, 95% CI: 3.432-12.020, P<0.001), hemorrhage (HR =0.514, 95% CI: 0.265-0.996, P=0.049) and TSR (HR =2.370, 95% CI: 1.264-4.443, P=0.007) were independent prognostic factors for MFS. Conclusions: TSR is a new independent prognostic risk factor for ccRCC patients. The assessment of TSR is simple and cost-effective, and it is a useful supplement added to the pathological evaluation system.

Robot-assisted Radical Prostatectomy with the KangDuo Surgical System Versus the da Vinci Si System: A Prospective, Double-center, Randomized Controlled Trial.

BACKGROUND: The KangDuo Surgical Robot (KD-SR) is a newly developed surgical robot. OBJECTIVE: To compare the safety and efficacy of robot-assisted radical prostatectomy (RARP) using the KD-SR with those of the da Vinci Si Surgical System (DV-SS-Si). DESIGN, SETTING, AND PARTICIPANTS: A prospective double-center noninferiority randomized controlled trial was conducted among 18-75-yr-old patients with suspected T1-2N0M0 prostate cancer (PCa) scheduled for RARP. INTERVENTION: RARP with the KD-SR (KD-RARP) versus RARP with the DV-SS-Si (DV-RARP). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was surgical success, defined as follows: surgery can be performed according to the established protocol, without switching to other surgical modalities, and without secondary surgery due to surgical complications after surgery. The secondary outcome was short-term functional and oncological outcomes. The noninferiority threshold was set at 10%. RESULTS AND LIMITATIONS: Eighty patients were enrolled, while the full analysis set finally included 79 patients (40 with KD-RARP and 39 with DV-RARP). The success rate was 100% in both groups. We could not find differences in urinary continence rate at 1, 2, 3, and 4 wk after catheter removal between the groups (p > 0.05). The rate of Clavien-Dindo grade II adverse events was 20% in the KD-RARP group and 17.9% in the DV-RARP group (p = 0.82), and no grade ≥III adverse events occurred. The median operation time was significantly longer in the KD-RARP group than in the DV-RARP group (177.5 vs 145 min, p = 0.012). The main limitations were the short follow-up period and that survival was not considered as the primary outcome. CONCLUSIONS: The KD-SR is a viable option for RARP, with acceptable short-term outcomes compared with the DV-SS-Si for T1-2 PCa. PATIENT SUMMARY: This is the first prospective randomized controlled trial to compare the KangDuo Surgical Robot (KD-SR) versus the da Vinci Si Surgical System (DV-SS-Si) for robot-assisted radical prostatectomy, which determines that the KD-SR is noninferior to the DV-SS-Si regarding safety and efficacy for T1-T2 prostate cancer.

A captivating approach to elevate the detection of Al3+ ions incorporates the utilization of a tripodal receptor intricately embellishing the surface of zinc oxide.

The FDA (Food and Drug Administration, (USA)) lists ZnO as a material that is widely acknowledged to be safe. ZnO NPs with a range of tiny particle sizes were made using the precipitation process. ZnO nanoparticles' surface is embellished with a tripodal sensor containing naphthol units. The assembly with the same receptor decorated on ZnO NPs is contrasted with the cation detection capabilities of the purified tripodal receptor. The UV-visible spectrophotometric analysis was conducted to study the state transitions of the receptor and the decorated ZnO receptor. A positive selectivity to Al3+ cations is determined by the fluorescence study under ideal circumstances. The particle size and surface morphologies are determined by DLS and SEM analysis for the same receptor - TP1 and embellished with a tripodal receptor TP2. Using a fluorescence switch-on Photoinduced Electron Transfer (PET) mechanism, the receptor coated on ZnO detects the presence of Al3+ ions with specificity. The binding constant value was determined using the B-H plot equation. Binding stoichiometry for [TP1-Al3+, TP2-Al3+] showed a 1:1 ratio. The fluorescence switches ON-OFF process of the ZnO surface adorned - TP2 with Tripodal receptor- TP1 was used to create molecular logic gates, which can function as a module for sensors and molecular switches. The addition of Na2EDTA in the solution of the [TP1; TP2 - Al3+] complex resulted in a noticeable reduction in the emission of fluorescence. This finding offers compelling support for the reversibility of the chemosensor. To enable the practical application of this sensor, we have developed a cassette containing receptors TP1 and TP2. Successfully, it can detect Al3+ metal ions. We performed a comprehensive assessment of the dependability and appropriateness of our approach in measuring the concentration of Al3+ ions in wastewater produced by important industrial procedures.

Impact of tumour stroma-immune interactions on survival prognosis and response to neoadjuvant chemotherapy in bladder cancer.

BACKGROUND: The tumour stroma is associated with unfavourable prognosis in diverse solid tumours, but its prognostic and predictive value in bladder cancer (BCa) is unclear. METHODS: In this multicentre, retrospective study, we included 830 patients with BCa from six independent cohorts. Differences in overall survival (OS) and cancer-specific survival (CSS) were investigated between high-tumour stroma ratio (TSR) and low-TSR groups. Multi-omics analyses, including RNA sequencing, immunohistochemistry, and single-cell RNA sequencing, were performed to study stroma-immune interactions. TSR prediction models were developed based on pelvic CT scans, and the best performing model was selected based on receiver operator characteristic analysis. FINDINGS: Compared to low-TSR tumours, high-TSR tumours were significantly associated with worse OS (HR = 1.193, 95% CI: 1.046-1.361, P = 0.008) and CSS (HR = 1.337, 95% CI: 1.139-1.569, P < 0.001), and lower rate of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). High-TSR tumours exhibited higher infiltration of immunosuppressive cells, including Tregs and tumour-associated neutrophils, while low-TSR tumours exhibited higher infiltration of immune-activating cells such as CD8+ Teff and XCR1+ dendritic cells. The TSR prediction model was developed by combining the intra-tumour and tumour base radiomics features, and showed good performance to predict high-TSR, as indicted by area under the curve of 0.871 (95% CI: 0.821-0.921), 0.821 (95% CI: 0.731-0.911), and 0.801 (95% CI: 0.737-0.865) in the training, internal validation, and external validation cohorts, respectively. In patients with low predicted TSR, 92.3% (12/13) achieved pCR, while only 35.3% (6/17) of patients with high predicted TSR achieved pCR. INTERPRETATION: The tumour stroma was found to be significantly associated with clinical outcomes in patients with BCa as a result of tumour stroma-immune interactions. The radiomics prediction model provided non-invasive evaluation of TSR and was able to predict pCR in patients receiving NAC for BCa. FUNDING: This work was supported by National Natural Science Foundation of China (Grant No. 82373254 and 81961128027), Guangdong Provincial Natural Science Foundation (Grant No. 2023A1515010258), Science and Technology Planning Project of Guangdong Province (Grant No. 2023B1212060013). Science and Technology Program of Guangzhou (SL2022A04J01754), Sun Yat-Sen Memorial Hospital Clinical Research 5010 Program (Grant No. SYS-5010Z-202401).

Feasibility and safety of dual-console telesurgery with the KangDuo Surgical Robot-1500 System using fifth-generation and wired networks: an animal experiment and sea-spanning clinical study.

BACKGROUND: To evaluate the feasibility and safety of dual-console telesurgery with the new KangDuo system in an animal experiment and clinical study. METHODS: Six canine models were performed radical prostatectomy with dual-console KanDuo surgical robot-1500 (KD-SR-1500-RARP). The perioperative outcomes, physical and mental workload of the surgeon were collected. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with NASA-TLX. After conducting animal experiments to verify safety of dual-console KD-SR-1500-RARP, we conducted the clinical trial using 5G and wired networks. RESULTS: In the animal experiment, all surgeries were performed successfully. The operative time was 80.2±32.1 min. The docking time was 2.4±0.5 min. The console time was 49.7±25.3 min. There were no perioperative complications or equipment related adverse events. All dogs can micturate after catheter removal at one week postoperatively. The mental workload was at a low level (a scale ranging from 0 to 60), which scored 15.7±6.9. Among the eight recorded muscles, the fatigue degree of the right radial flexor and left biceps was the highest two (iEMG, resection, 299.8±344 uV, 109.9±16.9 uV; suture, 849.4±1252.5 uV, 423.1±621.3 uV, respectively). In the clinical study, the console time was 136 min. The mean latency time was ≤200 ms. The data pocket loss was <1%. The operation was successfully completed without malfunctions occurring throughout the entire process. CONCLUSIONS: Dual-console telesurgery with the KD-SR-1500 system was shown to be feasible and safe in radical prostatectomy using 5G and wired networks.

Potential correlations between asymmetric disruption of functional connectivity and metabolism in major depressive disorder.

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.