The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Quantitative CT (QCT) is a method of measuring bone mineral density (BMD) of human based on a CT machine,calibrated by QCT body model and analyzed by professional software.Compared with dual-energy X-ray absorptiometry,QCT can not only assess the cortical and cancellous BMD but also exclude the influences of osteophytes and aortic/vascular calcification,thus being capable of accurately reflecting patients' bone mass.In recent years,increasing studies on QCT and osteoporosis (OP) have been carried out,and the application of QCT in the diagnosis of OP,evaluation of vertebral bone conditions,prediction of fracture risks,and assessment of anti-OP treatment is garnering increasing attention from researchers at home and abroad.This article reviews the research progress in this field,aiming to provide a reference for the research on QCT in the diagnosis and treatment of OP.
Humans ; Osteoporosis/diagnosis* ; Tomography, X-Ray Computed/methods* ; Bone Density

ObjectiveOur recent study has demonstrated that extracellular acidification promotes lipid accumulation in macrophages via the activation of acid sensing ion channel 1 (ASIC1), but the underlying mechanism remains unclear. This study aims to explore the effect of extracellular acidification on macrophage lipophagy and the underlying mechanism. MethodsRAW264.7 macrophages were incubated with 25 mg/Lox-LDL in a pH 6.5 culture medium for 24 h to build macrophage-derived foam cell models induced by extracellular acidification. Then, RAW264.7 macrophages were cultured in the acidic medium of pH 6.5 with or without PcTx-1 (ASIC1 specific blocker, 10 μg/L) or Nec-1 (RIP1 specific inhibitor, 20 μmol/L) for 24 h, intracellular lipid accumulation was observed by oil red O staining. The expressions of total ASIC1, plasma membrane ASIC1, RIP1, p-RIP1 Ser166, TFEB, p-TFEB Ser142, LC3 and p62 were measured by Western blot. The co-localization of lipids (indicated by Bodipy) with LC3II (autophagosomes) and LAMP1 (lysosomes) was analyzed by a confocal laser scanning microscopy, respectively. Morphological changes of lipophagy in the cells were observed by using transmission electron microscopy. ABCA1-mediated cholesterol efflux was determined by cholesterol fluorescence kits. ResultsCompared with pH 7.4+ox-LDL group, the intracellular lipid accumulation in the pH 6.5+ox-LDL group was significantly increased. Meanwhile, the expressions of plasma membrane ASIC1, p-RIP1 Ser166, p-TFEB Ser142, and p62 proteins were elevated significantly, while LC3II protein level and LC3II/LC3I ratio were decreased. Accordingly, compared with pH 7.4+ox-LDL group, the macrophage lipophagy of the pH 6.5+ox-LDL group was inhibited as indicated by the decreased localization of lipid droplets with LC3 and LAMP1, a decrease in the number of lipophagosomes as well as an increase in lipid droplets. Furthermore, ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from the macrophages of pH 6.5+ox-LDL group reduced dramatically. However, these above effects of extracellular acidification on RAW264.7 macrophages were abolished by PcTx-1 and Nec-1, respectively. ConclusionThese findings suggest extracellular acidification promotes the phosphorylation of TFEB at Ser142 via activating ASIC1/RIP1 pathway, thereby impeding lipophagy in RAW 264.7 macrophages, and that ASIC1 may be a new potential target for preventing aberrant lipid accumulation diseases including atherosclerosis.

The emergence and evolution of digital intelligent technology has profoundly influenced the development of minimally invasive research-oriented hepatobiliary and pancreatic surgery discipline. Over various periods, our team has always adhered to the principle of "being oriented by clinical issues and driven by clinical needs", continuously carried out innovative research across interdisciplinary boundaries, propelling the evolution of digital intelligent technology. Spanning over two decades, this journey includes the progression from digital virtual human, three-dimensional visualization, molecular fluorescence imaging, augmented reality and mixed reality, artificial intelligence, to the realm of human visualization meta-universe. This evolution facilitates the shift from two-dimensional empirical diagnoses of hepatobiliary and pancreatic surgical diseases to deep learning intelligent diagnostics, the transition from morphology-based tumor diagnoses to molecular imaging-based diagnostics, and from conventional empirical surgery to intelligent navigation surgery. The authors provide a comprehensive review of our developmental process and achievements within the realm of digital intelligent diagnostic and therapeutic technologies, with the aims to promote the development and application of digital intelligent medicine.

Objective:To explore the mediating role of working memory (WM) in the cortisol-awakening response (CAR) and multiple object tracking (MOT) in children with attention deficit hyperactivity disorder (ADHD).Methods:92 children with ADHD (ADHD group) and 94 typically developing children (control group) were selected from January 2022 to October 2022. Salivary cortisol levels were detected and analyzed in all children at four time points after awakening. Children's WM and MOT performance were assessed by the 1-back and MOT paradigms, respectively. SPSS 26.0 software was used for t-test and Pearson correlation analysis of the data, and plug-in PROCESS model 4 of SPSS 26.0 was used for mediated effects analysis. Results:(1) ADHD group showed significantly lower CAR, 1-back accuracy and MOT performance((30.97±5.63), (81.33±10.64) %, (2.36±0.37)) than the control group((32.41±3.48), (91.19±7.12) %, (2.62±0.28))( t=-2.09, -7.22, -5.31, all P<0.05). (2) Pearson analysis showed that CAR was positively correlated with 1-back accuracy ( r=0.293, P<0.01) and MOT performance ( r=0.740, P<0.01). 1-back accuracy was positively correlated with MOT performance ( r=0.368, P<0.01). (3) WM partially mediated the effect of CAR on MOT in children with ADHD, accounting for 6.13% (0.003/0.049) of the total effect. Conclusion:Children with ADHD have deficits in MOT.WM plays a mediating role between CAR and MOT performance in children with ADHD.

Objective:To observe the clinical effect of initiating continuous blood purification (CBP) treatment at different times for patients with severe acute pancreatitis (SAP), and to explore the optimal timing for starting CBP treatment for SAP, so as to provide evidence for clinicians to start CBP treatment.Methods:A retrospective cohort study was used to select patients with SAP who received CBP treatment in People's Hospital of Hunan Province from January 2020 to December 2023. According to the timing of CBP initiation, the patients were divided into early initiation group (diagnosis of SAP to the first CBP treatment time < 24 hours) and late initiation group (diagnosis of SAP to the first CBP treatment time of 24-48 hours). The general data, acute physiology and chronic health evaluationⅡ(APACHEⅡ), bedside index for severity in acute pancreatitis (BISAP) score and laboratory indicators, local complications and systemic complications, intensive care unit (ICU) treatment time, hospital stay, treatment cost, and clinical outcome of the two groups were collected and compared.Results:A total of 130 patients with SAP who received CBP treatment were enrolled, including 90 patients in the early initiation group and 40 patients in the late initiation group. Before treatment, there were no significant differences in gender, age, APACHEⅡscore, BISAP score, etiology and laboratory examination indexes between the early initiation group and late initiation group. At 48, 72, 96 hours after treatment, the blood calcium level of the two groups was significantly higher than that before treatment, and the levels of white blood cell count (WBC), C-reactive protein (CRP), lactic acid, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), APACHEⅡscore and BISAP score were significantly lower than those before treatment. The WBC level, APACHEⅡscore and BISAP score of the late initiation group were significantly lower than those of the early initiation group at 72 hours and 96 hours after treatment [WBC (×10 9/L): 10.96 (8.68, 13.04) vs. 12.45 (8.93, 16.30) at 72 hours after treatment, and 10.18 (8.68, 12.42) vs. 11.96 (8.81, 16.87) at 96 hours after treatment; APACHEⅡscore: 9.50 (5.75, 12.00) vs. 11.00 (6.25, 14.00) at 72 hours after treatment, and 10.00 (4.00, 12.00) vs. 12.00 (7.00, 14.75) at 96 hours after treatment; BISAP score: 2.35±1.03 vs. 2.76±1.10 at 72 hours after treatment, and 2.08±1.21 vs. 2.70±1.11 at 96 hours after treatment], the differences were statistically significant (all P < 0.05). In terms of complications, the incidence of pancreatic abscess in the late initiation group was significantly lower than that in the early initiation group [5.00% (2/40) vs. 20.00% (18/90)], but the incidence of abdominal compartment syndrome was significantly higher than that in the early initiation group [42.50% (17/40) vs. 13.33% (12/90)], the differences were statistically significant (all P < 0.05). In addition, the ICU treatment time in the early initiation group was significantly shorter than that in the late initiation group [days: 11.00 (6.00, 20.00) vs. 15.00 (9.75, 25.00), P < 0.05], and there were no statistically significant differences in hospitalization costs, length of stay and mortality between the two groups. Conclusions:CBP can effectively increase the level of blood calcium and decrease the level of lactic acid and inflammatory factors. Starting CBP within 24-48 hours after diagnosis of SAP can reduce WBC level and disease severity score faster, and reduce the occurrence of pancreatic abscess. Initiation of CBP within 24 hours after diagnosis of SAP can reduce the incidence of abdominal compartment syndrome and shorten the duration of ICU treatment.

Objective To explore the clinical efficacy of double beam double tunnel enhanced reconstruction technique in the treatment of knee anterior cruciate ligament(ACL)training injuries.Methods Twenty-nine cases of ACL injury of knee joint from January 2021 to December 2021 were retrospectively analyzed.All the cases were underwent ligament reconstruc-tion surgery.Cases were grouped by surgical technique:there were 14 patients in conventional reconstruction group,including 13 males and 1 female,aged from 22 to 31 years old with an average of(27.07±7.28)years old,autogenous hamstring tendon was used for ligament reconstruction.There were 15 patients in the enhanced reconstruction group,including 13 males and 2 females,aged from 25 to 34 years old with an average of(29.06±4.23)years old,double tunnel ligament reconstruction,the autogenous hamstring muscle was used as the anteromedial bundle,and the posterolateral bundle was replaced by a high-strength line.The difference between knee tibial anterior distance,Lysholm score,International Knee Literature Committee(IKDC)subjective score,Tegner motor level score and visual analog scale(VAS)at 6th and 12th months after the surgery,limb symmetry index(LSI)were recorded at the last follow-up and surgery-related adverse effects during follow-up.Results All patients were followed up,ranged from 13 to 15 months with an average of(13.7±0.8)months.There were no serious adverse reactions related to surgery during the period.There was no statistical difference between the preoperative general data and the observation index of the two groups(P＞0.05).The difference in tibial anterior distance at 6 and 12 months in the enhanced re-construction group(1.45±0.62)mm and(1.74±0.78)mm which were lower those that in the conventional reconstruction group(2.42±0.60)mm and(2.51±0.63)mm(P＜0.05).There was no significant difference in postoperative Lysholm score,Tegner motor level score,IKDC score,VAS,and limb symmetry index at the last follow-up(P＞0.05).Conclusion The enhanced recon-struction technique can more effectively maintain the stability of the knee joint and has no significant effect on the postoperative knee joint function compared with the traditional ligament reconstruction technique.The short-term curative effect is satisfac-tory,and it is suitable for the group with high sports demand.