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 Excavate the prescriptions containing the drug pair of Aurantii Fructus Immaturus-Magnoliae Officinalis Cortex(AFI-MOC),and statistically analyze the rules of prescription medication,and explore its potential mechanism of action in the treatment of food retention disorder.Methods The prescriptions containing the pair of AFI-MOC in the Great Dictionary of Traditional Chinese Medicine Prescriptions were retrieved and typed into Excel to establish a database.The source,dosage form,frequency of compatibility of traditional Chinese medicine,nature,taste and meridian attribution and indications were analyzed.Using R language(4.3.3)software with OriginPro to analysis co-occurrence frequency,association rule,correlation clustering analysis,and visualization.Then,the network construction,Protein-Protein Interaction Network(PPI)analysis,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment analysis of the"AFI-MOC-active ingredient-food retention disorder target"network were performed for the AFI-MOC drug pair and its indications food retention disorder.The binding between the core active ingredients and key target proteins was evaluated by molecular docking.Results A total of 349 prescriptions containing the pair of AFI-MOC were included,involving 267 Chinese herbs.Among them,the high-frequency compatibility drugs included Citri Reticulatae Pericarpium,Glycyrrhizae Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma,Rhei Radix et Rhizoma and Aucklandiae Radix.They are mainly warm in nature,spicy,bitter and sweet in taste,spleen,liver and stomach in meridian.There were 141 kinds of indications,most of which were diseases of the spleen and stomach system such as food retention disorder,dysentery and fullness.Correlation cluster analysis shows that the AFI-MOC drug pair is frequently combined with drugs that have the efficacy of promoting qi circulation,strengthening the spleen,clearing heat,and eliminating dampness.Found through the analysis of network pharmacology AFI-MOC drug pair on the core of the active ingredient of Luteolin,BU3,Naringenin,Honokiol and Nobiletin.Key targets for food retention disorder are BDNF,AKT1,ESR1,TNF and IL-6.Molecular docking results show Luteolin,combined with AKT1 is most closely.Conclusion AFI-MOC drug pair often compatible with Citri Reticulatae Pericarpium,Atractylodis Macrocephalae Rhizoma,Aucklandiae Radix.The advantages of the prescription containing AFI-MOC drug pair is food retention disorder.Its key active components can exert therapeutic effects through multiple targets such as AKT1 and TNF.This study reveals the AFI-MOC drug pair on compatibility laws,preliminary interpretation of the mechanism for the treatment of food retention disorder.It can provide references and a basis for studying the compatibility mechanism of AFI-MOC and guiding rational clinical medication.

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*

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

Objective Excavate the prescriptions containing the drug pair of Aurantii Fructus Immaturus-Magnoliae Officinalis Cortex(AFI-MOC),and statistically analyze the rules of prescription medication,and explore its potential mechanism of action in the treatment of food retention disorder.Methods The prescriptions containing the pair of AFI-MOC in the Great Dictionary of Traditional Chinese Medicine Prescriptions were retrieved and typed into Excel to establish a database.The source,dosage form,frequency of compatibility of traditional Chinese medicine,nature,taste and meridian attribution and indications were analyzed.Using R language(4.3.3)software with OriginPro to analysis co-occurrence frequency,association rule,correlation clustering analysis,and visualization.Then,the network construction,Protein-Protein Interaction Network(PPI)analysis,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment analysis of the"AFI-MOC-active ingredient-food retention disorder target"network were performed for the AFI-MOC drug pair and its indications food retention disorder.The binding between the core active ingredients and key target proteins was evaluated by molecular docking.Results A total of 349 prescriptions containing the pair of AFI-MOC were included,involving 267 Chinese herbs.Among them,the high-frequency compatibility drugs included Citri Reticulatae Pericarpium,Glycyrrhizae Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma,Rhei Radix et Rhizoma and Aucklandiae Radix.They are mainly warm in nature,spicy,bitter and sweet in taste,spleen,liver and stomach in meridian.There were 141 kinds of indications,most of which were diseases of the spleen and stomach system such as food retention disorder,dysentery and fullness.Correlation cluster analysis shows that the AFI-MOC drug pair is frequently combined with drugs that have the efficacy of promoting qi circulation,strengthening the spleen,clearing heat,and eliminating dampness.Found through the analysis of network pharmacology AFI-MOC drug pair on the core of the active ingredient of Luteolin,BU3,Naringenin,Honokiol and Nobiletin.Key targets for food retention disorder are BDNF,AKT1,ESR1,TNF and IL-6.Molecular docking results show Luteolin,combined with AKT1 is most closely.Conclusion AFI-MOC drug pair often compatible with Citri Reticulatae Pericarpium,Atractylodis Macrocephalae Rhizoma,Aucklandiae Radix.The advantages of the prescription containing AFI-MOC drug pair is food retention disorder.Its key active components can exert therapeutic effects through multiple targets such as AKT1 and TNF.This study reveals the AFI-MOC drug pair on compatibility laws,preliminary interpretation of the mechanism for the treatment of food retention disorder.It can provide references and a basis for studying the compatibility mechanism of AFI-MOC and guiding rational clinical medication.

Objective To explore the clinical value of apolipoprotein C1(APOC1)and Klotho expression levels in predicting the prognosis of patients with renal cancer after laparoscopic partial nephrectomy.Methods Eighty patients diagnosed as renal cell carcinoma and underwent laparoscopic partial nephrectomy were collected as the study subjects.According to the prognosis,patients were separated into the good prognosis group(61 cases)and the poor prognosis group(19 cases).Seventy-eight healthy individuals underwent physical examination were collected as the control group.The general clinical data of the subjects were collected,and serum levels of APOC1 and Klotho were tested and analyzed in three groups.Pearson method was applied to analyze the correlation between serum APOC1 and Klotho levels in patients.Cox regression was applied to analyze factors affecting the prognosis of patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive efficacy of APOC1 and Klotho levels on the prognosis of patients.Results There were significant differences in clinical stage and pathological grade between the poor prognosis group and the good prognosis group(P＜0.05).Compared with the control group,the serum APOC1 levels were significantly increased in the good prognosis group and the poor prognosis group(P＜0.05),while the Klotho expression levels were obviously reduced(P＜0.05).And the serum APOC1 level in the control group,the poor prognosis group and the good prognosis group was increased successively(P＜0.05),while the serum Klotho level was obviously decreased successively(P＜0.05).The serum APOC1 expression level of patients was negatively correlated with Klotho level(r=-0.577,P＜0.001).The Cox regression results showed that decreased expression level of Klotho and elevated expression level of APOC1,pathologic grading 2 and clinical staging stage Ⅱ were all independent risk factors for poor prognosis(P＜0.05).The area under the curve(AUC)of serum APOC1 and Klotho levels,and their combined application in predicting poor postoperative prognosis in renal cancer patients was 0.863,0.850 and 0.953,respectively,and the clinical value of combination of the two in predicting the prognosis of patients was superior to that of APOC1 and Klotho alone.Conclusion Patients with poor prognosis after retroperitoneal laparoscopic partial nephrectomy have a obvious increase in serum levels of APOC1 and a obvious decrease in serum level of Klotho.The combination of the two has high clinical significance in predicting the prognosis of patients with retroperitoneal laparoscopic partial nephrectomy.

Objective To explore the clinical value of apolipoprotein C1(APOC1)and Klotho expression levels in predicting the prognosis of patients with renal cancer after laparoscopic partial nephrectomy.Methods Eighty patients diagnosed as renal cell carcinoma and underwent laparoscopic partial nephrectomy were collected as the study subjects.According to the prognosis,patients were separated into the good prognosis group(61 cases)and the poor prognosis group(19 cases).Seventy-eight healthy individuals underwent physical examination were collected as the control group.The general clinical data of the subjects were collected,and serum levels of APOC1 and Klotho were tested and analyzed in three groups.Pearson method was applied to analyze the correlation between serum APOC1 and Klotho levels in patients.Cox regression was applied to analyze factors affecting the prognosis of patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive efficacy of APOC1 and Klotho levels on the prognosis of patients.Results There were significant differences in clinical stage and pathological grade between the poor prognosis group and the good prognosis group(P＜0.05).Compared with the control group,the serum APOC1 levels were significantly increased in the good prognosis group and the poor prognosis group(P＜0.05),while the Klotho expression levels were obviously reduced(P＜0.05).And the serum APOC1 level in the control group,the poor prognosis group and the good prognosis group was increased successively(P＜0.05),while the serum Klotho level was obviously decreased successively(P＜0.05).The serum APOC1 expression level of patients was negatively correlated with Klotho level(r=-0.577,P＜0.001).The Cox regression results showed that decreased expression level of Klotho and elevated expression level of APOC1,pathologic grading 2 and clinical staging stage Ⅱ were all independent risk factors for poor prognosis(P＜0.05).The area under the curve(AUC)of serum APOC1 and Klotho levels,and their combined application in predicting poor postoperative prognosis in renal cancer patients was 0.863,0.850 and 0.953,respectively,and the clinical value of combination of the two in predicting the prognosis of patients was superior to that of APOC1 and Klotho alone.Conclusion Patients with poor prognosis after retroperitoneal laparoscopic partial nephrectomy have a obvious increase in serum levels of APOC1 and a obvious decrease in serum level of Klotho.The combination of the two has high clinical significance in predicting the prognosis of patients with retroperitoneal laparoscopic partial nephrectomy.

X-linked adrenoleukodystrophy(X-ALD) is an inherited progressive neurometabolic disorder caused by mutations in the ATP-binding cassette subfamily D member 1(ABCD1) gene. The encoded ALD protein dysfunction leads to the accumulation of very-long-chain fatty acids(VLCFA). X-ALD is classified according to its clinical characteristics into childhood cerebral ALD, adolescent cerebral ALD, adult cerebral ALD, adrenomyeloneuropathy(AMN), pure adrenocortical insufficiency, and an asymptomatic phenotype, all of which can present with a variety of neurologic manifestations. In this study, we retrospectively analyzed the clinical manifestations, laboratory findings, genetic test results, and follow-up data of four patients with X-ALD, and investigated the clinical features and pathogenicity of the identified gene mutations. All four patients initially presented with adrenocortical insufficiency(Addison′s disease) and received glucocorticoid replacement therapy. Subsequently, all developed neurologic signs and symptoms with rapid progression. The final diagnosis was confirmed based on elevated VLCFA levels, brain magnetic resonance imaging(MRI) findings, and genetic analysis. Notably, a deletion mutation in Exon 10 of the ABCD1 gene was identified in one case for the first time. We report four cases of X-ALD presenting with adrenocortical insufficiency as the initial symptom, and briefly review the relevant literature to analyze the relationship between linical phenotypes and genetic loci, aiming to provide a reference for early diagnosis and treatment of the disease, and to reduce the risk of misdiagnosis and missed diagnosis.

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.