Hyperbaric Oxygen Boosts Antitumor Efficacy of Copper-Diethyldithiocarbamate Nanoparticles against Pancreatic Ductal Adenocarcinoma by Regulating Cancer Stem Cell Metabolism.

Cuproptosis-based cancer nanomedicine has received widespread attention recently. However, cuproptosis nanomedicine against pancreatic ductal adenocarcinoma (PDAC) is severely limited by cancer stem cells (CSCs), which reside in the hypoxic stroma and adopt glycolysis metabolism accordingly to resist cuproptosis-induced mitochondria damage. Here, we leverage hyperbaric oxygen (HBO) to regulate CSC metabolism by overcoming tumor hypoxia and to augment CSC elimination efficacy of polydopamine and hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@PH NPs). Mechanistically, while HBO and CuET@PH NPs inhibit glycolysis and oxidative phosphorylation, respectively, the combination of HBO and CuET@PH NPs potently suppresses energy metabolism of CSCs, thereby achieving robust tumor inhibition of PDAC and elongating mice survival importantly. This study reveals novel insights into the effects of cuproptosis nanomedicine on PDAC CSC metabolism and suggests that the combination of HBO with cuproptosis nanomedicine holds significant clinical translation potential for PDAC patients.

Hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals for cancer therapy.

Cancer stem cells (CSCs) have been recognized as the culprit for tumor progression, treatment resistance, metastasis, and recurrence while redox homeostasis represents the Achilles' Heel of CSCs. However, few drugs or formulations that are capable of elevating oxidative stress have achieved clinical success for eliminating CSCs. Here, we report hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanoparticles (CuET@HES NPs), which conspicuously suppress CSCs not only in vitro but also in numerous tumor models in vivo. Furthermore, CuET@HES NPs effectively inhibit CSCs in fresh tumor tissues surgically excised from hepatocellular carcinoma patients. Mechanistically, we uncover that hydroxyethyl starch stabilized copper-diethyldithiocarbamate nanocrystals via copper­oxygen coordination interactions, thereby promoting copper-diethyldithiocarbamate colloidal stability, cellular uptake, intracellular reactive oxygen species production, and CSCs apoptosis. As all components are widely used in clinics, CuET@HES NPs represent promising treatments for CSCs-rich solid malignancies and hold great clinical translational potentials. This study has critical implications for design of CSCs targeting nanomedicines.

A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism.

Cancer stem cells (CSCs) have been blamed as the main culprit of tumor initiation, progression, metastasis, chemoresistance, and recurrence. However, few anti-CSCs agents have achieved clinical success so far. Here we report a novel derivative of lonidamine (LND), namely HYL001, which selectively and potently inhibits CSCs by targeting mitochondria, with 380-fold and 340-fold lower IC50 values against breast cancer stem cells (BCSCs) and hepatocellular carcinoma stem cells (HCSCs), respectively, compared to LND. Mechanistically, we reveal that HYL001 downregulates glutaminase (GLS) expression to block glutamine metabolism, blunt tricarboxylic acid cycle, and amplify mitochondrial oxidative stress, leading to apoptotic cell death. Therefore, HYL001 displays significant antitumor activity in vivo, both as a single agent and combined with paclitaxel. Furthermore, HYL001 represses CSCs of fresh tumor tissues derived from liver cancer patients. This study provides critical implications for CSCs biology and development of potent anti-CSCs drugs.

Intelligent diagnostic model of keratoconus based on deep learning algorithm / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish an intelligent diagnostic model of keratoconus for small-diameter corneas by data mining and analysis of patients' clinical data.METHODS: Diagnostic study. A total of 830 patients(830 eyes)were collected, including 338 male(338 eyes)and 492 female(492 eyes), with an average age of 14-36(23.19±5.71)years. Among them, 731 patients(731 eyes)had undergone corneal refractive surgery at Chongqing Nanping Aier Eye Hospital from January 2020 to March 2022, and 99 patients had a diagnosed keratoconus from January 2015 to March 2022. Corneal diameter ≤11.1 mm was measured by Pentacam in all patients. Two cornea specialists classified patients' data into normal corneas, suspect keratoconus, and keratoconus groups based on the Belin/Ambrósio enhanced ectasia display(BAD)system in Pentacam. The data of 665 patients were randomly selected as the training set and the other 165 patients as the validation set by computer random sampling method. Seven parametric corneal features were extracted by convolutional neural networks(CNN), and the models were built by Residual Network(ResNet), Vision Transformer(ViT), and CNN+Transformer, respectively. The diagnostic accuracy of models was verified by cross-entropy loss and cross-validation method. In addition, sensitivity and specificity were evaluated using receiver operating characteristic curve.RESULTS: The accuracy of ResNet, ViT, and CNN+Transfermer for the diagnosis of normal cornea and suspect keratoconus was 85.57%, 86.11%, and 86.54% respectively, and the area under the receiver operating characteristic curve(AUC)was 0.823, 0.830 and 0.842 respectively. The accuracy of models for the diagnosis of suspect keratoconus and keratoconus was 97.22%, 95.83%, and 98.61%, respectively, and the AUC was 0.951, 0.939, and 0.988 respectively.CONCLUSION: For corneas ≤11.1 mm in diameter, the data model established by CNN+Transformer has a high accuracy rate for classifying keratoconus, which provides real and effective guidance for early screening.

Follow-up after renal transplantation / 中国医学科学院学报

Follow-up after renal transplantation is vital to improve allograft long-term survival and quality of life. This article describes the awareness, frequency, patterns, and contents of the follow-up after renal transplantation, especially 6 factors that may adversely influence the long-term survival of renal transplant recipients.

Prevalence and influential factors of erectile dysfunction in male renal transplant recipients: a multiple center survey / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Renal transplants can improve the quality of life for recipients, but the quality of their sexual life might not be improved. This study was conducted to research the prevalence of erectile dysfunction (ED) and the influential factors in male renal transplant recipients (RTRs).</p><p><b>METHODS</b>A cross-sectional survey was conducted in three renal transplantation centers. Structured questionnaires were administrated by trained interviewers to 824 male renal transplant patients, who had active sexual lives in the last 6 months.</p><p><b>RESULTS</b>Complaints of ED were reported by 75.5% of the 809 RTRs (age range 19 - 75 years, mean age (45 +/- 10) years), whose questionnaires were completed. Mild, moderate and severe ED were reported at 53.6%, 8.3% and 13.6%, respectively. The mean age and the graft duration were significantly higher in male RTRs with ED compared to potent graft recipients (P = 0.00 and 0.04, respectively). The prevalence of ED increased with the increase in age. It was 60.7%, 65.8%, 75.2%, 87.5% and 92.2% in patients with age below 30 years, 31 - 40 years, 41 - 50 years, 51 - 60 years and over 60 years, respectively (P = 0.000). Moreover, the severity of ED increased with aging. The percentage of moderate and severe cases of ED increased from 6.7% in patients below 40 years to 28.9% in those over 40 years (P = 0.000). The prevalence of ED in the RTR who had no occupation was higher than in those who were holding a position (P = 0.001). The prevalence of ED decreased with the increase in the education level. The prevalence of ED was 94.3%, 86.4%, 74.0% and 67.8% in men with elementary school or lower, middle school, high school, and college or higher degrees, respectively (P = 0.000). Patients, whose distal end of arteria iliaca interna was interrupted and underwent iterative transplantation, worried transplanted kidney function was impacted by sexual life, and received cyclosporine (CsA)-based immunosuppressive regimens, were more likely to have ED (P = 0.000, 0.001, 0.000, 0.000, respectively). After Logistic regression analysis, only five factors, age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life and CsA-based immunosuppressive regimens sustained their significance.</p><p><b>CONCLUSIONS</b>Renal transplant has varying effects on erectile function. ED is highly prevalent among RTRs and its influential factors are multiple. Age, education level, interruption of arteria iliaca interna distal end, worrying transplanted kidney function impacted by sexual life, CsA-based immunosuppressive regimens are the main influential factors of ED in male RTRs.</p>

Induction of apoptosis of peripheral activated T lymphocytes by immunosuppressants / 中华器官移植杂志

Objective To investigate the effects and mechanisms of immunosuppressants on in- duction of apoptosis of peripheral T lymphocytes.Methods T lymphocytes were derived from healthy donors and activated by super antigen SEB.The rest or activated T lymphocytes were incubated with immunosuppressants such as myophenolate mofetil (MMF),cyclosporine A (CsA),FK506,azathio- prine (Aza),sirolimus (SRL),prednisone (Pred),and daclizumab (Dac,anti-CD25mAb),alone or combined,for 3 days.The incidence of apoptosis was determined by the methods of confocal microsco- py,flow cytometer,DNA-ladder fragmentation electrophoresis,and reverse transcription-polymerase chain reaction (RT-PCR) gene amplification profiles.The quantitive assay of IL-2 and Fas in the cul- ture medium was also performed using the enzyme linked immunosorbent assay kit.Results Apoptosis in rest T lymphocytes was just induced by Pred among various immunosuppressants.MMF,Aza,and Pred promoted apoptosis in activated T lymphocytes (P＜0.05,P＜0.01),but it was blocked by CsA,FK506,SRL,and Dac (P＜0.01).After adding two or three kinds of immunosuppressants, the incidence of apoptosis in activated T lymphocytes was apparently lower than in control group (P＜0.01).The expression of Fas and IL-2 by activated T lymphocytes was inhibited by FK506 and CsA (P＜0.05).Conclusion MMF,Aza,and Pred may induce apoptosis of activated T lymphocytes via the signal pathway of Fas/Fasl.CsA and FK506 could inhibit the apoptosis of activated T lymphocytes by blocking the production of IL-2.Also,SRL and Dac can block the apoptosis of activated T lympho- cyte by interfering with the effect of IL-2 on T lymphocytes activation process.

DEEP FERMENTATION TECHNIQUE OF TRICHOLOMA MATSUTAKE MYCELIUM / 微生物学通报

The deep fermentation technique of Tricholoma matsutake is systemically studied in this paper firstly. The best culture determined by orthogonal test is 3g/L of cornflour, 1g/L of glucose, 1g/L of bean cake flour, 1mL/L of corn steep liquid, 1g/L of KH 2PO 4. The best fermenting condition is: 25℃, rotating speed 160 r/min, pH5.0,inoculating amount 10%, 120mL culture medium per 500mL flask. Under these conditions, the mycelia reach 12.94g/L after fermenting 12d.