Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

OBJECTIVE: To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed. METHODS: A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups. RESULTS: A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO₂, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO₂ (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH₂O, 1 cmH₂O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO₂, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO₂ (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×10⁹/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding. CONCLUSION Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans ; Retrospective Studies ; Extracorporeal Membrane Oxygenation/methods* ; Blood Transfusion, Autologous ; Male ; Female ; Adult ; Middle Aged ; Natriuretic Peptide, Brain/blood*

OBJECTIVE To explore the specific application and evaluation effect of objective structured clinical examination(OSCE)-guided scenario-based practical teaching mode in training clinical pharmacists. METHODS Fifty-six trainees who participated in the clinical pharmacist training program in the Second Xiangya Hospital of Central South University from October 2020 to September 2022 were selected as the research objects. OSCE-guided teaching was conducted, and the application effect of OSCE-guided teaching mode in clinical pharmacist training was explored and analyzed by using theoretical examination results and OSCE assessment results as evaluation indicators. RESULTS Through comparative analysis, it was found that the OSCE-guided teaching mode not only enabled students to better grasp the theoretical knowledge points required by the training outline, but also improved their clinical thinking ability, problem-solving ability, and communication and coordination skills to varying degrees. CONCLUSION For clinical pharmacist trainees, the OSCE teaching mode is conducive to the comprehensive improvement of clinical pharmacist skills and is suitable for cultivating clinical pharmacists who are capable of independently carrying out clinical pharmacy services in the new situation.

Objective:To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance.Methods:A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI.Results:A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHEⅡ score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day " n", with y = 1.246?2 x1.164?9 and an R2 of 0.860?1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day " n", with y = -0.260?6 x2+3.010?7 x-1.612 and an R2 of 0.998?9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 μmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. Conclusion:The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.

Chronic Guillain-Barre syndrome, also known as chronic inflammatory demyelinating polyradiculoneuropathy(CIDP), is an immune-mediated demyelinating peripheral neuropathy. This article analyzes the clinical data of a CIDP patient presenting primarily with limb numbness, pain, and weakness. Along with literature review, this study explores the differential diagnosis between CIDP and diabetic peripheral neuropathy in terms of the pathogenesis, clinical manifestations, laboratory tests, and treatment.

Objective To observe the value of cranial ultrasound for perioperative patients with acute severe traumatic brain injury(sTBI).Methods Data of 55 sTBI patients who underwent craniotomy were retrospectively analyzed.The patients were divided into observation group(n=15)and control group(n=40)according to received perioperative cranial ultrasound or not.The general data and surgical data were compared between groups,and ultrasonic data of observation group were analyzed.Results The proportions of good prognosis 1 and 6 months after operation in observation group were both higher than those in control group,while the incidence of cerebral infarction in observation group was lower than that in control group(all P＜0.05).No significant difference of general data nor other surgical data was found between groups(all P＞0.05).Acute encephalocele occurred in 1 case in observation group during operation,and cranial ultrasound accurately showed the contralateral secondary epidural hematoma.Increased intracranial pressure in different degrees were found in all 15 cases(15/15,100％)in observation group after operation with transcranial color coded Doppler(TCCD)or transcranial Doppler(TCD),while cerebral vascular spasm was observed in 5 cases(5/15,33.33％),among them 4 cases(4/5,80.00％)were diagnosed cerebral infarction based on CT examination.Conclusion Cranial ultrasound could be used to evaluate changes of sTBI in perioperative period and guide adjusting treatment strategy in time,being valuable for reducing risk of postoperative cerebral infarction and improving prognosis.

Objective To explore effect of Wenyang Qudu formula on serum inflammatory factors and immune index in patients with severe infections.Methods A total of 86 severe infection patients admitted to the Third People's Hospital of Henan Province from January to December 2023 were selected as the research subjects.According to the patient file order,odd numbers were the study group,and even numbers were the control group,with 43 cases in each group.The control group was treated with cefoperazone sulbactam sodium,while the study group was treated with Wenyang Qudu formula in addition to the control group[drug composition:Prepared aconite(first decocted)30 g,Poria cocos 30 g,White peony 15 g,Red peony 15 g,Stir fried atractylodes macrocephala 30 g,Dried ginger 9 g,Roasted licorice 9 g,Cassia twig 15 g,Semen lepidii 15 g,Dragon's bone 15 g,Raw oyster 15 g,Codonopsis pilosula 12 g,Angelica sinensis 12 g,Asarum 3 g,Schisandra chinensis 6 g,and Jujube 12 g].Brew in water,and took one dose daily,once in the morning and once in the evening,for a continuous period of 7 days.The differences in the scores of traditional Chinese medicine symptoms such as fever,dyspnea,frequent urination,urgency,and degree of sputum production,serum levels of interleukin-10(IL-10),C-reactive protein(CRP),eosinophils(EOS),and immune function indicators[immunoglobulin E(IgE),CD3+,CD4+,CD8+,CD4+/CD8+]were compared between two groups after treatment,and observed the occurrence of adverse reactions.Results After treatment,the traditional Chinese medicine symptom scores(fever,dyspnea,frequent urination and urgency,degree of sputum production),as well as IL-10,CRP,EOS levels,IgE,and CD8+ were significantly reduced in both groups compared to before treatment,CD3+,CD4+,and CD4+/CD8+ were significantly increased compared to before treatment.In addition,the study group had significantly lower scores of fever,dyspnea,frequent urination and urgency,degree of sputum production,IL-10,CRP,EOS levels,IgE,and CD8+ compared to the control group(fever score:1.36±0.30 vs.2.57±0.46,dyspnea score:1.22±0.31 vs.2.26±0.75,urinary frequency and urgency score:1.30±0.39 vs.2.33±0.82,degree of sputum production:1.19±0.77 vs.2.51±0.85,IL-10(ng/L):9.03±1.67 vs.10.51±2.40,CRP(mg/L):4.68±1.33 vs.7.82±2.53,EOS(×109/L):0.30±0.04 vs.0.46±0.10,IgE(mg/L):104.62±10.73 vs.135.68±14.64,CD8+:0.228±0.016 vs.0.258±0.020,all P<0.05],the levels of CD3+,CD4+,and CD4+/CD8+ were significantly higher than those in the control group(CD3+:0.636±0.044 vs.0.567±0.055,CD4+:0.537±0.054 vs.0.397±0.045,CD4+/CD8+:1.76±0.51 vs.0.55±0.39,all P<0.05].After treatment,it was discovered that the study group had not experienced any adverse reactions,while the control group had 1 case of nausea and vomiting and 1 case of chest tightness.There was no statistically significant difference in the incidence of adverse reactions between the study group and the control group[0(0/43)vs.0.05%(2/43),P>0.05].Conclusion The Wenyang Qudu formula can reduce the serum factor levels of IL-10,CRP,and EOS in critically infected patients,and improve immune function with good safety.

Recent findings from Diabetologia highlight the pivotal role of sialic acid-binding immunoglobulin-type lectin 1(SIGLEC-1) positive monocytes in the early onset of type 1 diabetes. These cells activate immune effector cells primarily via the interferon signaling pathway, diverging from traditional antigen presentation methods, thereby triggering pancreatic inflammation and destruction. This discovery paves the way for novel approaches in early diagnosis and targeted therapies for type 1 diabetes.

Mineralocorticoid receptor(MR) overactivation plays an important role in the development and progression of diabetic kidney disease(DKD) by mediating pro-inflammatory and pro-fibrotic processes, making it a key therapeutic target for DKD. Finerenone, a third-generation, highly selective, novel nonsteroidal mineralocorticoid receptor antagonist(MRA), mitigates MR overactivation through anti-inflammatory and anti-fibrotic effects and by improving the immune-inflammatory environment. This significantly reduces cardiovascular and renal composite endpoints in patients with type 2 diabetes mellitus(T2DM) and chronic kidney disease(CKD), and improve cardiorenal outcomes. Based on its novel molecular structure, Finerenone exhibits a lower incidence of adverse effects compared to the previous MRAs. This article elucidates the molecular structure and pathophysiological role of MR, and explores the molecular mechanisms through which finerenone provides cardiorenal benefits. It also discusses the advantages and safety of finerenone compared to first- and second-generation MRAs from a molecular structure perspective, providing evidence for its clinical application.