Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Objective:To discuss the effect of long non-coding RNA(lncRNA)DUXAP8 in exosomes(Exo)derived from the lung cancer A549 cells on the growth and immune escape of the lung cancer cells,and to clarify the mechanism.Methods:The human lung cancer cell line A549 was cultured,and its exosomes were extracted and identified.The A549 cells were treated with PKH67-labeled Exo to observe the uptake of Exo by A549 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of lncRNA DUXAP8 in A549 cells before and after Exo treatment.The A549 cells were divided into control group(no treatment),Exo group(A549 cells treated with Exo),Exo+sh-NC group(A549 cells treated with Exo and then transfected with sh-NC),and Exo+sh-DUXAP8 group(A549 cells treated with Exo and then transfected with sh-DUXAP8).RT-qPCR method was used to detect the expression level of lncRNA DUXAP8 in A549 cells in various groups;colony formation assay was used to detect the colony formation abilities of the A549 cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)staining method was used to detect the proliferation abilities of the A549 cells in various groups.After co-culturing A549 cells in various groups with human peripheral blood lymphocytes,flow cytometry was used to detect the percentages of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in various groups;3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)method was used to detect the killing rates of human peripheral blood lymphocytes on the A549 cells in various groups.Results:The diameter of Exo vesicles was 50-150 nm,and the exosome-specific marker proteins cluster of differentiation 63(CD63),cluster of differentiation 9(CD9),tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)were positively expressed,indicating successful exosome extraction.A549 cells efficiently took up PKH67-labeled Exo.The RT-PCR results showed that compared with A549 cells cultured alone,the expression level of lncRNA DUXAP8 in the A549 cells was increased after treatment with Exo derived from A549 cells(P<0.05).compared with control group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there were no significant difference in the expression level of IncRNA DUXAP8 in the cells in Exo+sh-NC group(P>0.05).The colony formation assay results showed that compared with control group,the number of colony formation of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the number of colony formation of the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the number of colony formation of the A549 cells in Exo+sh-NC group(P>0.05).The EdU staining results showed that compared with control group,the EdU-positive rate of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the EdU-positive rate in A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the EDU-positive rate in the cells in Exo+sh-NC group(P>0.05).The flow cytometry results showed that compared with control group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo group was decreased(P<0.05);compared with Exo group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo+sh-DUXAP8 group was increased(P<0.05),while there was no significant difference in the percentage of activated CD8+T lymphaytes in Exo+sh-NC group(P>0.05).The MTT assay results showed that compared with control group,the killing rate of human peripheral blood lymphocytes on the A549 cells in Exo group was decreased(P<0.05);compared with Exo group,the killing rate of human peripheral blood lymphocytes on A549 cells in Exo+sh-DUXAP8 group was increased(P<0.05),while no significant difference was observed in Exo+sh-NC group(P>0.05).Conclusion:The lncRNA DUXAP8 in exosomes derived from the lung cancer A549 cells promotes the proliferation of lung cancer cells and tumor immune escape.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

OBJECTIVE: To describe a novel arthroscopic technique of modified tri-anchor double-pulley suture-bridge in repairing medium-sized supraspinatus tendon tears and evaluate the early effectiveness. METHODS: Between June 2021 and January 2024, 26 patients with medium-sized supraspinatus tendon tears who underwent arthroscopic modified tri-anchor double-pulley suture-bridge repair and met the selective criteria were included. There were 11 males and 15 females with an average age of 61.4 years (range, 43-74 years). Five patients had a significant history of trauma, while the remaining 21 patients had no apparent cause. The time from symptom onset to hospitalization was 3-25 months (mean, 7.9 months). The effectiveness was evaluated during follow-up, including the scores of University of California at Los Angeles (UCLA), American Shoulder and Elbow Surgeons (ASES), visual analogue scale (VAS), the range of forward flexion, abduction, external rotation, and internal rotation, and patient's satisfaction. Either MRI or ultrasound examination were used to evaluate structural integrity of the tendon. RESULTS: The operation time was 65-110 minutes (mean, 81.8 minutes). All patients were followed up 12-43 months (mean, 23.0 months). At 3 and 12 months after operation, the shoulder range of flexion, abduction, external rotation, and internal rotation, and the scores of VAS, UCLA, and ASES significantly improved when compared with those before operation ( P<0.05). The improvement was further observed at 12 months compared to 3 months ( P<0.05). At last follow-up, 13 patients were very satisfied with the effectiveness, 11 patients were satisfied, 1 was relatively satisfied, and 1 was dissatisfied. During follow-up, 15 patients underwent imaging examination and imaging reexamination showed that the re-tear rate of tendon was 6.6%(1/15). The remaining 11 patients refused imaging examination. Complications included partial anchor withdrawal in 1 case, shoulder stiffness in 5 cases, and mild pain in shoulder joint in 2 cases in physical activity or heavy physical activity. CONCLUSION Arthroscopic modified tri-anchor double-pulley suture-bridge technique is a novel surgical technique that uses double-loaded suture anchors as medial- and lateral-row anchors. In repairing medium-sized supraspinatus tendon tears, 6 sets of double-pulley suture-bridges can be created from one medial-row anchor; knotless medial-row can reduce re-tear rate of the tendon; good early effectiveness is obtained.
Humans ; Female ; Male ; Middle Aged ; Arthroscopy/methods* ; Adult ; Rotator Cuff Injuries/surgery* ; Aged ; Suture Techniques ; Treatment Outcome ; Suture Anchors ; Rotator Cuff/surgery* ; Range of Motion, Articular ; Tendon Injuries/surgery* ; Patient Satisfaction