[Objective] To compare the clinical efficacy and safety of flexible ureteroscope lithotripsy (FURL) combined with flexible vacuum-assisted urethral access sheath (FV-UAS) and traditional UAS in the treatment of 1-2 cm lower renal calyceal stones, so as to provide reference for clinical practice. [Methods] Clinical data of 157 patients with 1-2 cm lower renal calyceal stones treated with FURL during Mar.2021 and Oct.2023 were retrospectively analyzed, including 80 treated with traditional UAS, and 77 with FV-UAS.General and clinical information of the two groups were compared. [Results] The immediate stone-free rate (SFR) (84.4% vs.67.5%, P=0.013) and final SFR (88.3% vs. 75.0%, P=0.032) of the FV-UAS group were significantly higher than those of the traditional UAS group, with significant difference.The incidence of postoperative complications such as fever, renal colic, and perirenal hematoma was significantly higher in the traditional UAS group than in the FV-UAS group (15.0% vs.5.2%, P=0.042). After treatment with anti-infective and analgesic drugs, both groups were improved, and no severe sepsis or septic shock occurred after surgery.The hospitalization expenses of the FV-UAS group were significantly lower than those of the traditional UAS group [ (18 341±1519)yuan vs.(19 152±1826)yuan, P=0.003]. [Conclusion] Compared to the traditional UAS, the combination of FURL and FV-UAS for the 1-2 cm lower renal calyceal stones has a high SFR and low incidence of complications.Patients experience less pain, recover faster and spend less.It's a new treatment option for inferior calyceal calculi.

This study explores the role and underlying molecular mechanisms of fucoidan sulfate(FPS) in regulating heme oxygenase-1(Hmox1)-mediated ferroptosis to ameliorate myocardial injury in diabetic cardiomyopathy(DCM) through in vivo and in vitro experiments and network pharmacology analysis. In vivo, a DCM rat model was established using a combination of "high-fat diet feeding + two low-dose streptozotocin(STZ) intraperitoneal injections". The rats were randomly divided into four groups: normal, model, FPS, and dapagliflozin(Dapa) groups. In vitro, a cellular model was created by inducing rat cardiomyocytes(H9c2 cells) with high glucose(HG), using zinc protoporphyrin(ZnPP), an Hmox1 inhibitor, as the positive control. An automatic biochemical analyzer was used to measure blood glucose(BG), serum aspartate aminotransferase(AST), serum lactate dehydrogenase(LDH), and serum creatine kinase-MB(CK-MB) levels. Echocardiography was used to assess rat cardiac function, including ejection fraction(EF) and fractional shortening(FS). Pathological staining was performed to observe myocardial morphology and fibrotic characteristics. DCFH-DA fluorescence probe was used to detect reactive oxygen species(ROS) levels in myocardial tissue. Specific assay kits were used to measure serum brain natriuretic peptide(BNP), myocardial Fe~(2+), and malondialdehyde(MDA) levels. Western blot(WB) was used to detect the expression levels of myosin heavy chain 7B(MYH7B), natriuretic peptide A(NPPA), collagens type Ⅰ(Col-Ⅰ), α-smooth muscle actin(α-SMA), ferritin heavy chain 1(FTH1), solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), 4-hydroxy-2-nonenal(4-HNE), and Hmox1. Immunohistochemistry(IHC) was used to examine Hmox1 protein expression patterns. FerroOrange and Highly Sensitive DCFH-DA fluorescence probes were used to detect intracellular Fe~(2+) and ROS levels. Transmission electron microscopy was used to observe changes in mitochondrial morphology. In network pharmacology, FPS targets were identified through the PubChem database and PharmMapper platform. DCM-related targets were integrated from OMIM, GeneCards, and DisGeNET databases, while ferroptosis-related targets were obtained from the FerrDb database. A protein-protein interaction(PPI) network was constructed for the intersection of these targets using STRING 11.0, and core targets were screened with Cytoscape 3.9.0. Molecular docking analysis was conducted using AutoDock and PyMOL 2.5. In vivo results showed that FPS significantly reduced AST, LDH, CK-MB, and BNP levels in DCM model rats, improved cardiac function, decreased the expression of myocardial injury proteins(MYH7B, NPPA, Col-Ⅰ, and α-SMA), alleviated myocardial hypertrophy and fibrosis, and reduced Fe~(2+), ROS, and MDA levels in myocardial tissue. Furthermore, FPS regulated the expression of ferroptosis-related markers(Hmox1, FTH1, SLC7A11, GPX4, and 4-HNE) to varying degrees. Network pharmacology results revealed 313 potential targets for FPS, 1 125 targets for DCM, and 14 common targets among FPS, DCM, and FerrDb. Hmox1 was identified as a key target, with FPS showing high docking activity with Hmox1. In vitro results demonstrated that FPS restored the expression levels of ferroptosis-related proteins, reduced intracellular Fe~(2+) and ROS levels, and alleviated mitochondrial structural damage in cardiomyocytes. In conclusion, FPS improves myocardial injury in DCM, with its underlying mechanism potentially involving the regulation of Hmox1 to inhibit ferroptosis. This study provides pharmacological evidence supporting the therapeutic potential of FPS for DCM-induced myocardial injury.
Animals ; Ferroptosis/drug effects* ; Rats ; Diabetic Cardiomyopathies/physiopathology* ; Male ; Rats, Sprague-Dawley ; Polysaccharides/pharmacology* ; Heme Oxygenase-1/genetics* ; Myocytes, Cardiac/metabolism* ; Myocardium/pathology* ; Humans ; Cell Line ; Heme Oxygenase (Decyclizing)

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

[Objective] To explore the efficacy of disposable flexible ureteroscopic lithotripsy (FURL) with flexible vacuum-assisted ureteral access sheath (FV-UAS) in the treatment of 2-3 cm upper urinary tract stones, so as to provide reference for the treatment selection. [Methods] Clinical data of 178 patients with upper urinary tract stones who received FURL or minimally invasive percutaneous nephrolithotomy (MPCNL) at our hospital during Apr. 2022 and Oct. 2023 were retrospectively analyzed. The patients were divided into FV-UAS group (n=90, received FV-UAS combined with diaposable FURL treatment) and MPCNL group (n=88, received MPCNL). The general information, perioperative data, and postoperative stone-free rate (SFR) of the two groups were compared. [Results] All operations were successfully completed. The operation time was significantly longer in the FV-UAS group than in the MPCNL group [(66.5±6.7) min vs. (63.9±7.4) min, P=0.015]. However, the intraoperative hemoglobin reduction [(7.3±3.1)g/L vs.(11.4±5.9)g/L], postoperative hospital stay (P<0.001) [(2.2±0.7)d vs.(5.4±1.3)d], and visual analogue score (VAS) [(2.7±0.9)vs.(5.6±1.1)] were significantly lower in the FV-UAS group than in the MPCNL group (P<0.001). The incidence of persistent gross hematuria was significantly higher in the MPCNL group than in the FV-UAS group (12.5% vs. 3.3%, P=0.023). The FV-UAS group had a similar postoperative immediate (83.3%) and final SFR (95.6%) to those of the MPCNL group (89.8%, 96.6%, P>0.05). [Conclusion] The combination of FURL with FV-UAS for 2-3 cm upper urinary tract stones has a higher SFR and a lower complication rate.Patients experience endurable pain and fast recovery, which is worth promoting and applying in clinical practice.

Objective To investigate the value of a nomogram model based on contrast-enhanced CT radiomics in predicting the histological type of thymoma.Methods A total of 154 patients(101 in low-risk group and 53 in high-risk group)with thymoma confirmed by pathology were retrospectively selected.The cases were randomly divided into training set(n=107)and validation set(n=47)at a ratio of 7∶3.The three-dimensional volume of interest(VOI)of the whole lesion on the image from the arterial phase of contrast-enhanced CT was manually delineated,and the radiomics features were extracted.Based on the selected radiomics features,the radiomics model was constructed and the model Radiomics score(Radscore)was calculated.Clinical risk factors were screened to construct a clinical model,and a nomogram model was constructed by fusing Radscore and clinical risk factors.The receiver operating characteristic(ROC)curve,area under the curve(AUC),accuracy,sensitivity and specificity were compared to analyze the predictive efficacy and difference of different models for high-risk and low-risk thymoma.The decision curve and calibration curve were drawn to evaluate the clinical value and fitting performance of the nomogram model.Results Eleven radiomics features were selected to construct the radiomics model,and five clinical risk factors[myasthenia gravis(MG),morphology,border,surrounding tissue invasion and CT value in arterial phase]were used to construct the clinical model.In the training set,the AUC of the nomogram model(0.88)was higher than that of the radiomics model(0.80)and the clinical model(0.79),and the difference was statistically significant(Z=2.233,2.713,P=0.026,0.007,respectively).In the validation set,the AUC of the nomogram model was higher than that of the radiomics and clinical models,but the difference was not statistically significant.The calibration curve showed that the nomogram model had good fitting performance,and the decision curve showed that the nomogram model had high clinical benefit.Conclusion The nomogram model based on contrast-enhanced CT can effectively predict high-risk and low-risk thymoma,which is helpful to guide clinicians to make relevant decisions.

Objective:To investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) examination in clinical diagnosis of gallbladder tumor with perigallbladder invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 80 gallbladder tumor patients with perigallbladder invasion who were admitted to 3 medical centers (21 cases in The First Affiliated Hospital of Northwest University, 42 cases in The First Affiliated Hospital of the Air Force Medical University, 17 cases in The First Affiliated Hospital of Dalian Medical University) from January 2021 to December 2022 were collec-ted. There were 45 males and 35 females, aged (56±4)years. Observation indicators: (1) CT and MRI examinations; (2) surgical conditions. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) CT and MRI examinations. Of 80 patients, cases with gallbladder cancer and gallbladder adenoma were 73 and 7, respectively. Cases with endoluminal nodular type, mass type and localized thick-walled type were 33, 39 and 8, respectively, with tumor diameter as 1.55 cm×1.35 cm×1.33 cm, 1.64 cm×1.37 cm×1.36 cm and 5.72 cm×4.07 cm×4.36 cm. Results of CT examination of endoluminal nodular type showed local nodular protrusions into the endoluminal area, and local enhancement on enhanced scanning. Results of CT examination of localized thick-walled type showed the cavity wall of lesion was locally or diffusely irregul-arly thickened, with a thickness of 1.10(range, 1.10-2.21)cm. Of 80 patients, results of CT and MRI examinations showed invasion of liver parenchyma in 68 cases, which was manifested as local mass, blurred demarcation, and abnormal protrusion. The maximum depth was (4.22±0.25)cm, (4.22±0.22)cm, (4.28±0.16)cm of cross-sectional, coronal, sagittal view in CT examination, respectively. The minimum depth was (0.22±0.10)cm, (0.25±0.08)cm, (0.24±0.12)cm. The depth of liver parenchyma invaded was (1.64±1.38)cm, (1.68±1.46)cm, (1.66±1.40)cm. Results of CT and MRI examinations showed invasion of perigallbladder, which was manifested as local invasion of the gastric antrum in 12 cases. (2) Surgical conditions. Of 80 patients, results of CT and MRI examina-tions showed that 60 patients had localized masses in the gallbladder cavity with or without infiltration of surrounding tissues. After confirming the absence of other organs and distant metastasis, cases undergoing radical resection and palliative resection were 44 and 16, respectively. Results of CT and MRI examina-tions showed that 20 patients had malignant gallbladder tumors with peri-pheral liver infiltration and multiple intrahepatic metastases with distant organ metastases, which were unresectable.Conclusion:For patients with gallbladder cancer and perigallbladder invasion, CT or MRI examina-tions can show their structural characteristics.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective To investigate the effect of sarcopenia on the efficacy of percutaneous kyphoplasty(PKP)in the treatment of osteoporotic spinal compression fracture(OSCF)in elderly patients. Methods From February 2017 to June 2018,a total of 77 elderly patients who met the inclusion and exclusion criteria were included in this study.Grip strength of dominant hand was measured by an electronic grip dynamometer with cut-off values of 27 kg for males and 16 kg for females.The cross-sectional area of the pedicle level muscle of the 12th thoracic vertebra(T12)was measured by chest CT.The skeletal muscle index(SMI)was calculated by dividing the T12 pedicle level muscle cross-sectional area by the square of body height.The SMI cut-off value used to diagnose sarcopenia was 42.6 cm
Aged ; Female ; Fractures, Compression/surgery* ; Humans ; Kyphoplasty ; Male ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Sarcopenia/complications* ; Spinal Fractures ; Treatment Outcome

Objective:To evaluate the risk factors related to the mid-term outcomes of hip preserving surgery for early stages osteonecrosis of the femoral head (ONFH) basing on China-Japan Friendship Hospital (CJFH) classification system.Methods:From June 2012 to September 2016, there were consecutive 325 patients (432 hips) were enrolled and divided into different preserving surgery groups, namely core decompression (CD) group 141 hips and "lightbulb" operation (LB) group 291 hips, respectively. Harris hip score (HHS) was used to evaluate the clinical outcomes. The progression of ONFH was observed by radiography. Clinical failure was defined as worsen of HHS and/or radiographic evaluation. Clinical endpoint events were marked as significant hip pain (HHS<70), and/or collapse of the femoral head requiring further interventions. Potential risk factors, including sex, age, etiology, the duration from symptom onset to treatment, preoperative CJFH type, ARCO stage and HHS, were analyzed using univariate risk analysis and Cox regression multivariate risk model.Results:The rate of hip failure was 47.5% (67/141) in CD group, including type C+M 13.0% (3/23), L1 38.1% (24/63), L2 82.4% (14/17) and L3 68.4% (26/38), respectively. There was significant difference in age (χ 2=3.887, P=0.049), type of CJFH (χ 2=40.943, P=0.000) in CD group. The Cox regression analysis revealed that age≥40 ( HR=2.325, 95% CI 1.398, 3.866, P=0.000), pre-HHS 70-80 ( HR=2.163, 95% CI 1.140, 4.105, P=0.018) and <70 ( HR=2.597, 95% CI 1.173, 5.749, P=0.019), type L2 ( HR=35.052, 95% CI 7.721, 159.133, P=0.000) and L3 ( HR=13.242, 95% CI 3.104, 56.491, P=0.000) were associated with failure of core decompression. The rate of hip failure was 36.4%(106/291) in LB group, including type C+M 33.3% (1/3), L1 31.3% (41/131), L2 84.6% (22/26) and L3 32.1% (42/131), respectively. There were significant differences in age (χ 2=8.437, P=0.004), pre-HHS (χ 2=19.737, P=0.000) and type of CJFH (χ 2=29.265, P=0.000) in LB group. The Cox regression analysis showed that poor pre-HHS ( HR=5.102, 95% CI 2.339, 11.129, P=0.000), type L2 ( HR=32.761, 95% CI 6.165, 43.507, P=0.000) were associated with failure of "lightbulb" preserving surgery. Conclusion:The results of hip preserving surgery for ONFH are associated with age, preoperative HHS and CJFH typing. The prognosis depends on the severity of symptoms, the residual of weight-bearing joint surface and lateral pillar of the femoral head.

Proteases are enzymes that cleave and hydrolyse the peptide bonds between two specific amino acid residues of target substrate proteins. Protease-controlled proteolysis plays a key role in the degradation and recycling of proteins, which is essential for various physiological processes. Thus, solving the substrate identification problem will have important implications for the precise understanding of functions and physiological roles of proteases, as well as for therapeutic target identification and pharmaceutical applicability. Consequently, there is a great demand for bioinformatics methods that can predict novel substrate cleavage events with high accuracy by utilizing both sequence and structural information. In this study, we present Procleave, a novel bioinformatics approach for predicting protease-specific substrates and specific cleavage sites by taking into account both their sequence and 3D structural information. Structural features of known cleavage sites were represented by discrete values using a LOWESS data-smoothing optimization method, which turned out to be critical for the performance of Procleave. The optimal approximations of all structural parameter values were encoded in a conditional random field (CRF) computational framework, alongside sequence and chemical group-based features. Here, we demonstrate the outstanding performance of Procleave through extensive benchmarking and independent tests. Procleave is capable of correctly identifying most cleavage sites in the case study. Importantly, when applied to the human structural proteome encompassing 17,628 protein structures, Procleave suggests a number of potential novel target substrates and their corresponding cleavage sites of different proteases. Procleave is implemented as a webserver and is freely accessible at http://procleave.erc.monash.edu/.