The n-butanol fraction of Alpinia oxyphylla Fructus 70% ethanol extract was separated and purified using column chromatography with MCI Gel CHP-20, Sephadex LH-20, ODS, and silica gel, combined with semi preparative liquid phase and TLC separation methods. One new halogenated 4,5-seco-eudesmane sesquiterpenoid and two new eremophilane sesquiterpenoids were isolated and purified from the n-butanol fraction of Alpinia oxyphylla Fructus. The structures of the isolated compounds were identified using modern spectroscopic methods (1D, 2D NMR, UV, IR, MS, etc.), and the absolute configuration of the new compounds were determined using the methods of calculated ECD and induced ECD.

The synergistic antibacterial strategy of peroxidase mediated chemodynamic therapy(CDT)and photothermal therapy(PTT)has been proven to effectively resist bacteria.However,the antibacterial effect against Pseudomonas aeruginosa is severely limited due to the factors such as short lifespan of reactive oxygen species(ROS)(<200 ns)and limited diffusion distance(about 20?200 nm).In this study,glucopyranose functionalized MoO3-x(P-MoO3-x)nanoenzyme was successfully synthesized using a one-pot hydrothermal method.This nanoenzyme exhibited both peroxidase-like activity and a photothermal effect.The combined antibacterial performance and biological safety of P-MoO3-x was analyzed and verified.By utilizing specific interactions with glucopyranose and lectin,P-MoO3-x nanoenzyme could target the surface of Pseudomonas aeruginosa.This targeted approach effectively shortened the range of hydroxyl radicals,significantly enhancing the antibacterial effect against Pseudomonas aeruginosa.Under photothermal action,P-MoO3-x could reach the optimal reaction effect at 70℃.Even at low concentrations of hydrogen peroxide(50 μmol/L),it released more hydroxyl radicals.In vitro antibacterial analysis experiments demonstrated that the inactivation efficiency of the P-MoO3-x antibacterial system against Pseudomonas aeruginosa(106 CFU/mL)exceeded 99%.Furthermore,in vivo experiments confirmed the significant therapeutic effects of P-MoO3-x in treating methicillin-resistant Staphylococcus aureus(MRSA)infected wounds and promoting wound healing,without producing toxicity to cells.In conclusion,P-MoO3-x exhibited excellent antibacterial ability and good biocompatibility,making it a promising anti-infective nanoenzyme with broad application prospects.

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Leukemia, Promyelocytic, Acute/therapy* ; Prognosis ; Myelodysplastic Syndromes/drug therapy* ; Neoplasms, Second Primary/drug therapy* ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis (ALS). Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020. Healthy adults from a community were recruited as healthy controls. Muscle strength was assessed using the Medical Research Council (MRC) scale. At the first visit to the hospital, patients were assessed for maximal grade of fasciculations, total fasciculation score, and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography. The sensitivity and specificity of maximal grade of fasciculations, total fasciculation score, and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses. Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9% and 9.8%, respectively (χ² = 172.436, P < 0.01). Of the 16 limb muscles detected, the total fasciculation score [median (interquartile range)] was 29 (15, 41) in ALS patients and 3 (0, 8) in neuropathy-radiculopathy patients (Z = 9.642, P < 0.001). Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4, followed by patients with MRC score 5, and then in those with MRC score 0 and 1. The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6% and 93.4%, respectively (cut-off value 14). In patients with ALS, for muscles with MRC score 4 and 5, the percentage of muscles with fasciculation grades ≥ 3 was 42.3% and 24.1% respectively, while in neuropathy-radiculopathy patients, the percentage for muscles with MRC score 4 and 5 was only 1.7% and 0, respectively. Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
Adult ; Humans ; Amyotrophic Lateral Sclerosis/diagnostic imaging* ; Fasciculation/diagnostic imaging* ; Radiculopathy ; Muscle, Skeletal/diagnostic imaging* ; Ultrasonography/methods*

Objective: To develop effective alternatives to natural enzymes, it is crucial to develop nanozymes that are economical, resource efficient, and environmentally conscious. Carbon nanomaterials that have enzyme-like activities have been extensively developed as substitutes for traditional enzymes. Methods: Carbide-derived carbons (CDCs) were directly synthesized via a one-step electrochemical method from a MAX precursor using an ammonium bifluoride electrolyte at ambient conditions. The CDCs were characterized by systematic techniques. Results: CDCs showed bienzyme-like activities similar to that of peroxidase and superoxide dismutase. We systematically studied the dependence of CDC enzyme-like activity on different electrolytes and electrolysis times to confirm activity dependence on CDC content. Additionally, the synthesis mechanism and CDC applicability were elaborated and demonstrated, respectively. Conclusion The demonstrated synthesis strategy eliminates tedious intercalation and delamination centrifugation steps and avoids using high concentrations of HF, high temperatures, and halogen gases. This study paves the way for designing two-dimensional material-based nanocatalysts for nanoenzyme and other applications.
Ammonium Compounds/chemical synthesis* ; Carbon/chemistry* ; Electrochemical Techniques ; Enzymes ; Fluorides/chemical synthesis* ; Humans ; Nanostructures ; Oxidation-Reduction

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 analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.
China ; Female ; Humans ; Kidney Diseases, Cystic/genetics* ; Kidney Failure, Chronic/genetics* ; Male ; Phenotype ; Proteinuria/genetics* ; Retrospective Studies

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Objective: To observe the changes of parameters derived from transthoracic echocardiography (TTE) before and after left ventricular assist device (LVAD) implantation, and to evaluate the clinical value of TTE in the perioperative period of LVAD implantation. Methods: This is a retrospective study. The data of patients who underwent LVAD implantation in Fuwai Hospital from January 2018 to December 2020 were analyzed retrospectively. The TTE parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin (TBil) before and 1 month after LVAD implantation were collected and analyzed. Results: A total of 12 male patients undergoing LVAD implantation were included in this study. The mean age was (43.3±8.6) years. The left atrial volume index ((41.4±12.8)ml/m² vs. (74.9±30.7)ml/m², P<0.001), left ventricular end-diastolic volume index ((152.1±35.3)ml/m² vs. (205.5±35.7)ml/m², P<0.001), left ventricular end-systolic volume index ((112.5±27.9)ml/m² vs. (155.1±29.1)ml/m², P<0.001), right atrial diameter index ((23.7±3.5)mm/m² vs. (27.2±5.8)mm/m², P=0.023), right ventricular internal diameter at end-diastole ((24.6±2.7)mm vs. (30.0±4.8)mm, P<0.001), tricuspid annular plane systolic excursion ((11.5±2.9)mm vs. (14.6±2.8)mm, P=0.007), systolic pulmonary arterial pressure ((29.2±4.8) mmHg vs. (55.1±19.3) mmHg, P<0.001, 1 mmHg=0.133 kPa) were significantly reduced at 1 month post LVAD implantation as compared to before LVAD implantation. The aortic sinus diameter ((33.8±4.7)mm vs. (31.6±5.1)mm, P=0.007), left ventricular ejection fraction ((26.3±3.0)% vs. (23.8±4.4)%, P=0.016), right ventricular fractional area change ((31.0±8.6)% vs. (23.8±5.5)%, P=0.004) at 1 month post LVAD implantation were significantly higher than before LVAD implantation. The degree of mitral and tricuspid regurgitation decreased, and the inspiratory collapse rate of inferior vena cava increased (all P<0.05). NT-proBNP ((1 418.4±812.6)ng/L vs. (5 097.5±3 940.4)ng/L, P=0.004) and TBil ((12.4±5.4)μmol/L vs. (27.5±14.0)μmol/L, P=0.001) decreased significantly at 1 month post LVAD implantation. Conclusions: TTE results show that LVAD could effectively relieve left ventricular load and improve right ventricular function. TTE can monitor the cardiac structural and functional changes during the perioperative period of LVAD implantation, and provide the imaging evidence for clinical evaluation of the therapeutic effect of LVAD.
Adult ; Echocardiography ; Heart Failure/surgery* ; Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Perioperative Period ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left