ObjectiveTo reveal the active substances and mechanisms of modified Qing'e formula （MQEF） in delaying skin photoaging by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS），network pharmacology， and cell experiments. MethodsUPLC-Q-TOF-MS and a literature review were employed to analyze the transdermally absorbed components in mice after the topical application of MQEF. The potential targets of MQEF in treating skin photoaging were retrieved from databases.The compound-potential target network and protein-protein interaction network were constructed to screen the key components and core targets. A photoaging cell model was established by irradiating HaCaT cells with medium-wave ultraviolet B （UVB）. The safe doses of bakuchiol （BAK） and salvianolic acid B （SAB） for treating HaCaT cells and the effects of BAK and SAB on the viability of cells exposed to UVB irradiation were determined by the cell counting kit-8 （CCK-8） method.The reactive oxygen species （ROS） fluorescent probe was used to measure the ROS production in the cells treated with BAK and SAB.The expression levels of genes related to oxidative stress，inflammation，collagen metabolism，and circadian rhythm clock were measured by Real-time PCR. ResultsA total of 24 transdermally absorbed components of MQEF were identified，which acted on 367 potential targets，and 417 targets related to skin photoaging were screened out，among which 47 common targets were predicted as the targets of MQEF in treating skin photoaging. MQEF exerted the anti-photoaging effect via key components such as BAK and SAB，which acted on core proteins such as serine/threonine kinase 1 （Akt1） and mitogen-activated protein kinase 3 （MAPK3） and intervened in core pathways such as the tumor necrosis factor （TNF） and phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathways.Compared with the model group，the administration of BAK and SAB increased the survival rate of HaCaT cells （P<0.01），down-regulated the mRNA levels of cyclooxygenase-2 （COX-2），interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），matrix metalloproteinase-1 （MMP-1），and matrix metalloproteinase-9 （MMP-9） （P<0.01），and up-regulated the mRNA levels of heme oxygenase-1 （HO-1） and NAD（P）H quinone dehydrogenase 1 （NQO-1） （P<0.05，P<0.01） in photoaged HaCaT cells.In addition，it eliminated excess ROS production induced by UVB and up-regulated the mRNA levels of brain and muscle ARNT-like 1 （BMAL1） and circadian locomotor output cycles kaput （CLOCK） associated with circadian clock （P<0.05，P<0.01）. ConclusionMQEF delays skin photoaging through the coordinated effects of various components，multiple targets，and diverse pathways.The key components BAK and SAB in MQEF exhibit anti-photoaging properties，which involve inhibiting oxidative stress，preventing collagen degradation，mitigating inflammation，and maintaining normal skin circadian rhythms by regulating clock gene expression.

ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer （OC） cells and the regulatory mechanism of gypenoside L （Gyp-L） on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 （CCK-8） assay， and the half-maximal inhibitory concentration （IC₅₀） values of cisplatin （DDP）， Gyp-L， and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs （tsRNAs） in the cells after Gyp-L intervention， and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde （MDA）， glutathione （GSH）， and lipid peroxide （LPO） levels were measured by colorimetry or enzyme linked immunosorbent assay （ELISA） method， Fe²⁺ content by FerroOrange fluorescent probe， and reactive oxygen species （ROS） content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group， a 50 µmol·L^-1 Gyp-L group， and a 100 µmol·L^-1 Gyp-L group. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the expression of mature-tRNA-Asp-GTC， mature-tRNA-Leu-CAA， mature-mt_tRNA-Tyr-GTA_5_end， mature-tRNA-Val-CAC， mature-mt_tRNA-Glu-TTC， pre-tRNA-Arg-TCT， mature-tRNA-Asn-GTT， hydroxymethylbilane synthase （HMBS）， Wnt， β-catenin， glutathione peroxidase 4 （GPX4）， Kelch-like ECH-associated protein 1 （KEAP1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， activating transcription factor 3 （ATF3）， cystine/glutamate antiporter xCT， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Western blot was performed to detect the expression of HMBS， Wnt， β-catenin， GPX4， KEAP1， Nrf2， ATF3， xCT， LPCAT3， and ALOX15 proteins. ResultsThe 50 µmol·L^-1 Gyp-L， 100 µmol·L^-1 Gyp-L， DDP， 50 µmol·L^-1 Gyp-L+DDP， and 100 µmol·L^-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells （P<0.05） and exacerbated cell ferroptosis as reflected by the increase in the content of ROS， MDA， LPO， and Fe²⁺， as well as a decrease in the content of GSH （P<0.05）. Compared with the control group， Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells （P<0.05， |log₂Fc|>1）. Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention （P<0.05）. ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.

ObjectiveTo investigate the role of mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in the ferroptosis phenotype of ovarian cancer （OC） cells and the regulatory mechanism of gypenoside L （Gyp-L） on mature-tRNA-Asp-GTC and pre-tRNA-Arg-TCT in OC cells. MethodsThe proliferation of human ovarian adenocarcinoma OVCAR3 cells was detected by cell counting kit-8 （CCK-8） assay， and the half-maximal inhibitory concentration （IC₅₀） values of cisplatin （DDP）， Gyp-L， and DDP in the presence of Gyp-L were calculated to determine the intervention concentration for subsequent experiments. Cell cloning assay and scratch assay reflected the proliferation and migration ability of OVCAR3 cells. PANDORA-seq small RNA sequencing was used to detect the differentially expressed transfer RNA-derived small RNAs （tsRNAs） in the cells after Gyp-L intervention， and the corresponding target genes of the tsRNAs were found by the RNAhybrid software. Malondialdehyde （MDA）， glutathione （GSH）， and lipid peroxide （LPO） levels were measured by colorimetry or enzyme linked immunosorbent assay （ELISA） method， Fe²⁺ content by FerroOrange fluorescent probe， and reactive oxygen species （ROS） content by DCFH-DA fluorescent probe to reflect the occurrence of ferroptosis in OVCAR3 cells. OVCAR3 cells were divided into a control group， a 50 µmol·L^-1 Gyp-L group， and a 100 µmol·L^-1 Gyp-L group. Quantitative real-time polymerase chain reaction （PCR） was performed to detect the expression of mature-tRNA-Asp-GTC， mature-tRNA-Leu-CAA， mature-mt_tRNA-Tyr-GTA_5_end， mature-tRNA-Val-CAC， mature-mt_tRNA-Glu-TTC， pre-tRNA-Arg-TCT， mature-tRNA-Asn-GTT， hydroxymethylbilane synthase （HMBS）， Wnt， β-catenin， glutathione peroxidase 4 （GPX4）， Kelch-like ECH-associated protein 1 （KEAP1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， activating transcription factor 3 （ATF3）， cystine/glutamate antiporter xCT， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Western blot was performed to detect the expression of HMBS， Wnt， β-catenin， GPX4， KEAP1， Nrf2， ATF3， xCT， LPCAT3， and ALOX15 proteins. ResultsThe 50 µmol·L^-1 Gyp-L， 100 µmol·L^-1 Gyp-L， DDP， 50 µmol·L^-1 Gyp-L+DDP， and 100 µmol·L^-1 Gyp-L+DDP groups showed significantly inhibited proliferation and migration of OVCAR3 cells （P<0.05） and exacerbated cell ferroptosis as reflected by the increase in the content of ROS， MDA， LPO， and Fe²⁺， as well as a decrease in the content of GSH （P<0.05）. Compared with the control group， Gyp-L effectively interfered with the expression of 25 tsRNAs in OVCAR3 cells （P<0.05， |log₂Fc|>1）. Pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/NRF2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/NRF2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 axial expression was significantly aberrant after Gyp-L intervention （P<0.05）. ConclusionThe pre-tRNA-Arg-TCT/HMBS/Wnt/β-catenin/GPX4， pre-tRNA-Arg-TCT/KEAP1/Nrf2/xCT， mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT， and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling pathways are involved in OC development. Gyp-L inhibits OC development by activating OVCAR3 cell ferroptosis onset mainly through the mature-tRNA-Asp-GTC/ATF3/KEAP1/Nrf2/xCT and mature-tRNA-Asp-GTC/LPCAT3/ALOX15 signaling axes.

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.
Artificial Intelligence ; Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Deep Learning ; Diagnostic Imaging/methods*

At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*

Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans ; Liver Cirrhosis/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Circadian Rhythm/drug effects* ; Animals ; Medicine, Chinese Traditional ; Hepatic Stellate Cells/drug effects*

OBJECTIVE: To compare the effectiveness of different puncture methods of the flexible bone cement delivery device in unilateral percutaneous curved vertebroplasty for osteoporotic vertebral upper 1/3 compression fractures. METHODS: A retrospective analysis was conducted on the clinical data of 67 patients with osteoporotic vertebral upper 1/3 compression fractures who were admitted and met the selection criteria between January 2023 and April 2024. The patients were divided into two groups based on the puncture method of the flexible bone cement delivery device: the oblique puncture group ( n=37) and the parallel puncture group ( n=30). There was no significant difference ( P>0.05) between the two groups in terms of gender, age, bone mineral density (T value), distribution of fractured vertebrae, time from injury to operation, and preoperative visual analogue scale (VAS) score for pain, Oswestry disability index (ODI), anterior vertebral height of the fractured vertebra, and Cobb angle of the fractured vertebra. The following parameters were compared between the two groups: operation time, incidence of secondary puncture, incidence of bone cement leakage, volume of injected bone cement, bone cement distribution score, as well as VAS score, ODI, anterior vertebral height of the fractured vertebra, and Cobb angle of the fractured vertebra at 1 day after operation and at last follow-up. RESULTS: Two cases in the oblique puncture group and 7 cases in the parallel puncture group underwent secondary puncture during operation, and the difference in the incidence of secondary puncture was significant ( P<0.05). No complications such as bone cement hypersensitivity, bone cement embolism, nerve injury, or epidural hematoma occurred in both groups. There was no significant difference in operation time, volume of injected bone cement, incidence of bone cement leakage, distribution score and rating of bone cement between the two groups ( P>0.05). All patients were followed up 6-18 months (mean, 12.0 months), and there was no significant difference in the follow-up time between the two groups ( P>0.05). No further fracture collapse or compression occurred in the fractured vertebra during follow-up. Both groups exhibited significant improvements in VAS score, ODI, anterior vertebral height, and Cobb angle of the fractured vertebra after operation compared to baseline ( P<0.05). There were also significant differences between the two time points after operation ( P<0.05). However, there was no significant difference in the above indicators between the two groups ( P>0.05). CONCLUSION For osteoporotic vertebral upper 1/3 compression fractures treated with unilateral percutaneous curved vertebroplasty, both oblique and parallel puncture methods of the flexible bone cement delivery device can effectively relieve pain, but the former is more conducive to reducing the incidence of secondary puncture.
Humans ; Bone Cements/therapeutic use* ; Fractures, Compression/surgery* ; Retrospective Studies ; Vertebroplasty/instrumentation* ; Osteoporotic Fractures/surgery* ; Spinal Fractures/surgery* ; Female ; Male ; Aged ; Middle Aged ; Treatment Outcome ; Punctures/methods* ; Aged, 80 and over

OBJECTIVE: To analyze the efficacy and safety of decitabine-based myeloablative preconditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML). METHODS: The clinical characteristics and efficacy of 115 AML patients who underwent allo-HSCT at the First Medical Center of Chinese PLA General Hospital from August 2018 to August 2022 were retrospectively analyzed, including 37 patients treated with decitabine conditioning regimen (decitabine group) and 78 patients without decitabine conditioning regimen (non-decitabine group). The cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and graft versus host disease (GVHD) were analyzed. RESULTS: For the patients in first complete remission (CR1) state before allo-HSCT, the 1-year relapse rates of decitabine group(22 cases) and non-decitabine group(69 cases) were 9.1% and 29.6%, respectively, the difference was statistically significant(P =0.042). The 1-year cumulative incidence of acute graft-versus-host disease (aGVHD) in decitabine group and non-decitabine group was 62.2% and 70.5%, respectively, and the 1-year cumulative incidence of chronic inhibitor-versus-host disease (cGVHD) was 18.9% and 14.1%, respectively, there were no significant differences in the incidence of aGVHD and cGVHD between the two groups (P >0.05). Of the 115 patients, there were no significantly differences in the 1-year CIR(21.7% vs 28.8%, P =0.866), NRM(10.9% vs 3.9%, P =0.203), OS(75.2% vs 83.8%, P =0.131) and LFS(74.6% vs 69.1%, P =0.912) between the decitabine group(37 cases) and the non-decitabine group(78 cases). CONCLUSION Decitabine-based conditioning regimen could reduce the relapse rate of AML CR1 patients with good safety.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/methods* ; Decitabine/therapeutic use* ; Transplantation Conditioning/methods* ; Retrospective Studies ; Graft vs Host Disease ; Transplantation, Homologous ; Male ; Female ; Adult ; Middle Aged ; Adolescent ; Young Adult

OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

Objective:This study explored the effect of nanoparticle-encapsulated curcumin on the highly expressed multidrug resistance gene 1 （MDR1） in a human low-differentiated nasopharyngeal carcinoma cell line （CNE2）. Methods:Curcumin/chitosan deoxycholic acid nanoparticles were prepared, and the cells were subjected to different treatments: radiotherapy, empty carriers, curcumin, and curcumin-loaded nanoparticles. Cell survival was analyzed using the clonogenic assay, and assessments of apoptosis, MDR1 levels, and miR593 levels were conducted. Results:The cell survival fractions in the curcumin group and the curcumin-loaded nanoparticles group were significantly reduced. Notably, higher apoptosis rates were observed in cells treated with curcumin or curcumin-loaded nanoparticles compared to those that received only radiotherapy. Moreover, a decreased MDR1 level was noted in both the curcumin group and the curcumin-loaded nanoparticles group, with further reduction in MDR1 expression observed in the nanoparticle group （P<0.05）. Enhanced expression of miR593 was found in the curcumin group and the curcumin-loaded nanoparticles group, with a relatively higher level in the nanoparticle group （P<0.05）. Curcumin encapsulated in nanoparticles exhibited a stronger radiosensitizing effect. The combination of curcumin and radiotherapy effectively inhibited nasopharyngeal carcinoma （NPC） tumor growth, suppressed MDR1 expression, and enhanced miR593 levels. After inhibiting miR593, MDR1 expression increased. The radiosensitizing effect of curcumin-loaded nanoparticles was regulated by miR593 rather than being triggered by MDR1. Conclusion:Curcumin-loaded nanoparticles mediated enhanced expression of miR593, which in turn inhibited the transcription and translation of the MDR1 gene, thereby reducing the radioresistance of NPC and effectively restraining its growth.
Humans ; Curcumin/pharmacology* ; Nasopharyngeal Neoplasms/pathology* ; Nasopharyngeal Carcinoma ; Nanoparticles ; Cell Line, Tumor ; Apoptosis/drug effects* ; MicroRNAs ; ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism* ; Cell Survival