In recent years, gastrointestinal stromal tumors (GIST) have increased incidence and mortality, and most GIST is caused by the activation mutation of the c-KIT gene. Therefore, c-KIT has become a promising therapeutic target of GIST. At present, the drugs approved for the treatment of GIST including imatinib, sunitinib, regorafenib and ripretinib, are mostly prone to developing resistance and accompanied by various degrees of adverse reactions. Therefore, there is an urgent need to develop new c-KIT inhibitors to solve the problem of resistance. In this study, we investigated the anti-tumor effect of a novel c-KIT inhibitor PN17-1 on gastrointestinal stromal tumor GIST-882 cells in vitro. We found that PN17-1 significantly inhibited the proliferation, colony formation and migration ability of GIST-882 cells, and significantly downregulated the protein expression levels of p-c-KIT and its downstream signals p-AKT, p-STAT5 and p-ERK in GIST-882 cells. In addition, PN17-1 induced apoptosis in GIST-882 cells, and the apoptosis may be mainly related to the mitochondrial-dependent endogenous pathway. In conclusion, the novel c-KIT inhibitor PN17-1 is a promising anti-GIST drug, and this study provides new ideas for further development of c-KIT inhibitors in the future.

As traditional Chinese medicine （TCM） culture evolves， the academic thoughts of these practitioners， being a core component of TCM inheritance， are gradually shifting from traditional models to digital and intelligent approaches. However， this process faces challenges， including insufficient standardization of data collection and processing， low inheritance efficiency， and the risk of inheritance alienation. To address these issues， this paper proposed the construction of an intelligent platform following the "intelligence-transmission-modeling-linkage" path. "Intelligence" involves using smart perception technologies to accurately collect and classify diagnostic and therapeutic information from famous TCM practitioners， laying the foundation for digital inheritance； "transmission" focuses on leveraging artificial intelligence to mine and inherit the clinical experience of famous TCM practitioners， thereby establishing a "regional academic schools+group commonality" dynamic inheritance system； "modeling" integrates the academic thoughts and advantageous diseases of multiple schools to develop intelligent diagnostic and therapeutic models of famous TCM practitioners， resulting in personalized treatment plans； "linkage" involves constructing a clinical decision support system of famous TCM practitioners by integrating blockchain and generative intelligence， creating an AI digital avatar of TCM diagnostic and therapeutic knowledge. The "intelligence-transmission-modeling-linkage" intelligent inheritance model not only provides new ideas for the digital inheritance of TCM academic schools， but also offers strong support for the modernization and internationalization of TCM.

ObjectiveTo investigate the effects of rhizosphere organic acids secreted by the roots of Salvia miltiorrhiza on continuous cropping obstacles. MethodsThe mixed solution of organic acids in the rhizosphere of S. miltiorrhiza in continuous cropping and rotation cropping was added to the hairy roots subcultured for 21 days， and samples were collected on days 0， 2， 4， 6， 8， and 10. The changes of biomass， effective components， primary metabolites， secondary metabolites， antioxidant enzymes， and hormones in hairy roots of S. miltiorrhiza were observed and determined. ResultsCompared with the rotation cropping group and the blank control group， the simulation of organic acid secretion from the roots of S. miltiorrhiza had a significant inhibitory effect on the growth of hairy roots and decreased the content of effective components as well as total sugar and total protein in primary metabolites. Compared with the blank control group， the rotation cropping group and the continuous cropping group showed total sugar and total protein content decreases of 33.9% and 5.1%， respectively. On the other hand， the secretion of organic acids from S. miltiorrhiza roots significantly promoted the accumulation of total phenolic acids and total tanshinone， which showed increases of 14.6% and 1.6%， respectively， in continuous cropping group and rotation cropping group compared with the blank control group. ConclusionThe organic acid environment under continuous cropping significantly inhibited the growth of hairy roots and the accumulation of primary metabolites， while promoting the synthesis and accumulation of secondary metabolites of S. miltiorrhiza.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Capsules ; Carcinoma/drug therapy*

The seed kernel of Momordica cochinchinensis, i.e., Momordicae Semen, is used for medicinal purposes, but to date, no research has been reported on its chemical constituents. In this study, the chemical constituents of Momordicae Semen were investigated for the first time using silica gel column chromatography, semi-preparative HPLC, HR-MS, and NMR. As a result, eight compounds were isolated and identified as: p-hydroxybenzoic acid-7-O-trehaloside(mubeside A, 1), 2,6-dimethoxyphenol-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside B, 2), 1-O-p-methoxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside C, 3), 1-O-p-hydroxybenzoyl-1,4-benzenediol-4-O-β-D-apiosyl-(1→2)-β-D-glucoside(mubeside D, 4), gypsogenin-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(5), quillaic acid-3-O-β-D-galactosyl-(1→2)-β-D-glucuronoside(6), violanthin(7), and kaempferitrin(8). Compounds 1-4 are new compounds, while compounds 5-8 were isolated from Momordicae Semen for the first time.
Glycosides/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Molecular Structure ; Magnetic Resonance Spectroscopy ; Chromatography, High Pressure Liquid

In this study, serum metabolomics techniques and molecular biology methods were used to investigate the intervention effect of kaji-ichigoside F1 on chronic unpredictable mild stress(CUMS) depression mouse model and its mechanism. The CUMS depression mouse model was constructed, and the mice were divided into blank group, model group, escitalopram(ESC, 10 mg·kg~(-1)) group, and low-dose, medium-dose, and high-dose kaji-ichigoside F1 groups(1, 2, and 4 mg·kg~(-1)). CUMS modeling was performed on all mice except the blank group, and the cycle was four weeks. At the end of modelling, ESC and kaji-ichigoside F1 were administered by gavage once a day for 28 days. After the end of the administration, behavioral testing(sucrose preference test, open field test, forced swimming test, and tail suspension test) was conducted to evaluate the improvement of depression symptoms of different doses of kaji-ichigoside F1 on CUMS depression mouse model. The morphology of neurons and the number of Nissl bodies in the hippocampus were observed by Nissl staining. Metabolomics technique was used to analyze the changes in serum differential metabolites in mice. Protein expression levels of P2X7 purinergic receptor(P2X7R), adenosine A1 receptor(A1R), and adenosine receptor A2A(A2AR) in mouse hippocampus were detected by Western blot. The results showed that compared with that in the blank group, the body weight of mice in the model group was significantly decreased, and the sucrose preference rate was significantly decreased. The immobility time was significantly increased in the forced swimming and tail suspension tests, and the total moving distance was significantly decreased in the open field test. The number of Nissl bodies was significantly decreased, and the depression-like behavior and the number of Nissl bodies in the hippocampus of mice were significantly improved after administration of kaji-ichigoside F1. In the metabonomics analysis, the purine metabolism of serum after kaji-ichigoside F1 administration was involved in the metabolic passage of depression, and Western blot analysis verified the expression of P2X7R, A1R, and A2AR proteins in purine metabolic pathways. The results show that kaji-ichigoside F1 significantly decreases the expression of P2X7R and A2AR proteins in the hippocampus of CUMS model mice and increases the expression level of A1R proteins. It is suggested that kaji-ichigoside F1 may play an antidepressant role by regulating the expression of P2X7R, A1R, and A2AR proteins in the purine metabolism pathway.
Animals ; Mice ; Antidepressive Agents/administration & dosage* ; Metabolomics ; Depression/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Disease Models, Animal ; Hippocampus/metabolism* ; Behavior, Animal/drug effects* ; Humans

OBJECTIVE: To investigate of effectiveness of free fascia lata flap assisted by indocyanine green angiography (ICGA) in treatment of Myerson type Ⅱ and Ⅲ chronic Achilles tendon ruptures. METHODS: A clinical data of 14 patients with Myerson type Ⅱ and Ⅲ chronic Achilles tendon ruptures between March 2020 and June 2024 was retrospectively analyzed. All Achilles tendon defects were repaired with the free fascia lata assisted by ICGA during operation. There were 12 males and 2 females with an average age of 45.4 years (range, 26-71 years). The causes of Achilles tendon rupture included sports injury in 10 cases, Achilles tendon-related tendinopathy in 3 cases, and glass laceration injury in 1 case. The time from Achilles tendon rupture to operation was 4-40 weeks (median, 4.5 weeks). Preoperative MRI examination showed that the defect length of the Achilles tendon was 2-5 cm (mean, 3.2 cm). The operation time and intraoperative blood loss were recorded. The color Doppler ultrasound (CDU) and MRI were taken to observe the foot blood vessels and the tendon healing. The visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, Achilles Tendon rupture score (ATRS), and range of motion of the ankle joint were used to estimate the pain and function of ankle joint. RESULTS: All operations of the 14 patients were successfully completed. The operation time ranged from 3.00 to 4.50 hours (mean, 3.60 hours). The intraoperative blood loss ranged from 10 to 50 mL (mean, 36.4 mL). After operation, 1 patient had exudation at the recipient site, which healed after dressing change; the other incisions healed by first intention. All incisions at the donor sites healed by first intention. All patients were followed up 6-36 months (mean, 11.4 months). The CDU of the foot at 1 month after operation showed that the blood flow signal of the perforating vessels of the fascia lata flap was clear. The ankle MRI at 2 months after operation showed the good continuity of the Achilles tendon. No complication such as the Achilles tendon re-rupture, ankle stiffness, or scar contracture occurred during follow-up. Compared with preoperative score, the AOFAS score, ATRS score, and plantar flexion range of motion significantly increased at 1, 3, and 6 months after operation ( P<0.05), while the VAS score and dorsiflexion range of motion significantly decreased ( P<0.05). The AOFAS score, ATRS score, and VAS score at 3 and 6 months further improved when compared with those at 1 month ( P<0.05); however, there was no significant difference in the range of motion of the ankle joint ( P>0.05). There was no significant difference in above indicators between 3 and 6 months after operation ( P>0.05). CONCLUSION The treatment of Myerson type Ⅱ and Ⅲ chronic Achilles tendon ruptures with free fascia lata flaps under the guidance of ICGA has the advantages of precise design, fast healing, and a wide range of adaptability.
Humans ; Achilles Tendon/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Indocyanine Green ; Rupture/surgery* ; Aged ; Fascia Lata/transplantation* ; Angiography/methods* ; Free Tissue Flaps/blood supply* ; Plastic Surgery Procedures/methods* ; Tendon Injuries/diagnostic imaging* ; Treatment Outcome ; Chronic Disease

OBJECITVE: To investigate the effectiveness of three-dimensional (3D) printing-assisted vascularized fibular graft for repairing metatarsal defects. METHODS: Between November 2021 and February 2024, 11 patients with varying degrees of metatarsal defects caused by trauma were treated. There were 10 males and 1 female, aged 22-67 years, with a mean age of 51.2 years. The defect locations were as follows: the first metatarsal in 4 cases, the fifth metatarsal in 2 cases, the first and the second metatarsals in 1 case, the first to third metatarsals in 1 case, the third and the fourth metatarsals in 1 case, the third to fifth metatarsals in 1 case, and the first to fifth metatarsals in 1 case. The preoperative American Orthopaedic Foot & Ankle Society (AOFAS) score was 67.0 (48.5, 72.5). Based on 3D-printed bilateral feet models and mirrored healthy-side foot arch angles for preoperative planning and design, the vascularized fibular graft was performed to repair the metatarsal defects. At last follow-up, the medial and lateral longitudinal arches of bilateral feet were measured on weight-bearing X-ray films, and functional assessment was conducted using the AOFAS score. RESULTS: All operations were successfully completed, with an operation time ranging from 180 to 465 minutes (mean, 246.8 minutes). All incisions healed by first intention, with no occurrence of osteomyelitis. All patients were followed up 6-22 months (mean, 10 months). X-ray film reviews showed bone graft healing in all cases, with a healing time of 3-6 months (mean, 5 months). All patients underwent internal fixator removal at 6-12 months after operation. At last follow-up, no significant difference was observed in the medial and lateral longitudinal arches between the healthy and affected feet ( P>0.05). The AOFAS score of the affected foot was 78.0 (73.5, 84.0), showing a significant improvement compared to the preoperative score ( P<0.05). The effectiveness was rated as excellent in 1 case, good in 7 cases, fair in 2 cases, and poor in 1 case. Linear scarring remained at the donor site, with no functional impairment in adjacent joint movement. CONCLUSION 3D printing-assisted vascularized fibular graft for repairing metatarsal defects can effectively restore the physiological angle of the foot arch, facilitate the recovery of weight-bearing alignment, promote good bone healing, and yield satisfactory clinical outcomes.
Humans ; Printing, Three-Dimensional ; Middle Aged ; Male ; Fibula/blood supply* ; Female ; Metatarsal Bones/injuries* ; Adult ; Bone Transplantation/methods* ; Aged ; Plastic Surgery Procedures/methods* ; Young Adult ; Treatment Outcome

OBJECTIVE: To investigate the clinical efficacy of bilateral targeted puncture in percutaneous vertebroplasty(PVP) based on the vertebral osteodense zone. METHODS: A retrospective analysis was conducted on 76 patients with fresh symptomatic osteoporotic vertebral compression fractures, characterized by the presence of a dense zone, who underwent percutaneous vertebroplasty (PVP) between January 2021 and December 2021. All patients involved single-level vertebral fractures. There were 19 males and 57 females, aged from 62 to 88 years old, with an average of (68.5±12.5) years old. All patients underwent bilateral transpedicular puncture procedures. Preoperative CT or MRI was utilized to ascertain the relative position of the bone osteodense zone within the vertebral body (specifically, whether this zone is situated in the upper one-third or one-quarter of the left or right sagittal plane). Considering the head and tail regions of the dense zone as puncture targets, the puncture points and paths were meticulously planned, and the working channel was subsequently established. Under continuous monitoring by a C-arm X-ray machine, bone cement was carefully and gradually injected. The operation time, bone cement injection volume, and bone cement leakage were recorded. The visual analogue scale (VAS) and Oswestry disablity index (ODI) were used to evaluate the effectiveness of the operation. ODI and anterior height (AH) of the vertebral body were used to evaluate the efficacy. RESULTS: All patients successfully completed the surgery and were followed up for (8.0±1.0) months. The operation time was (36.57±11.25) min, the volume of bone cement injection was(6.07±1.19) ml, and 21 patients of bone cement leakage. There were 3 patients with the VAS exceeded 4 points two days postoperatively, indicating suboptimal pain management. At the three time points of pre-operation, 2 days post-operation and 6 months post-operation, the VAS scores were(7.82±1.29), (2.11±0.44), and (2.04±0.67) respectively;the ODI percentages were(75.65±7.23)%, (29.45±4.16)%, and(28.68±5.62)%;and the AH values were (11.02±1.30), (12.87±3.91), and (12.91±3.86) cm. The differences were all statistically significant(P<0.05). The aforementioned three indices demonstrated significant improvement at both 2 days and 6 months post-operation (all P<0.05). There were no statistically significant differences in these indices between the 2-day and 6-month post-operative periods(P>0.05). The postoperative outcome was satisfactory and durable, with no evidence of vertebral height reduction. CONCLUSION Bilateral targeted puncture based on the osteodense dense zone within the vertebral body can achieve bilateral symmetrical and upright full vertebral bone cement reinforcement without increasing bone cement leakage, achieving good early efficacy and preventing late vertebral collapse. This has positive significance for further improving the efficacy of percutaneous vertebroplasty.
Humans ; Male ; Female ; Vertebroplasty/methods* ; Aged ; Middle Aged ; Aged, 80 and over ; Retrospective Studies ; Spinal Fractures/surgery* ; Fractures, Compression/surgery* ; Punctures ; Bone Cements ; Osteoporotic Fractures/surgery*