Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed

In this paper, near-infrared spectroscopy(NIRS) was employed to analyze 129 batches of commercial products of Reduning Injection. The batch reporting rate was estimated according to the report of Reduning Injection in the direct adverse drug reaction(ADR) reporting system of the drug marketing authorization holder of the Center for Drug Reevaluation of the National Medical Products Administration(National Center for ADR Monitoring) from August 2021 to August 2022. According to the batch reporting rate, the samples of Reduning Injection were classified into those with potential risks and those being safe. No processing, random oversampling(ROS), random undersampling(RUS), and synthetic minority over-sampling technique(SMOTE) were then employed to balance the unbalanced data. After the samples were classified according to appropriate sampling methods, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA), uninformative variables elimination(UVE), and genetic algorithm(GA) were respectively adopted to screen the features of spectral data. Then, support vector machine(SVM), logistic regression(LR), k-nearest neighbors(KNN), naive bayes(NB), random forest(RF), and artificial neural network(ANN) were adopted to establish the risk prediction models. The effects of the four feature extraction methods on the accuracy of the models were compared. The optimal method was selected, and bayesian optimization was performned to optimize the model parameters to improve the accuracy and robustness of model prediction. To explore the correlations between potential risks of clinical use and quality test data, TreeNet was employed to identify potential quality parameters affecting the clinical safety of Reduning Injection. The results showed that the models established with the SVM, LR, KNN, NB, RF, and ANN algorithms had the F1 scores of 0.85, 0.85, 0.86, 0.80, 0.88, and 0.85 and the accuracy of 88%, 88%, 88%, 85%, 91%, and 88%, respectively, and the prediction time was less than 5 s. The results indicated that the established models were accurate and efficient. Therefore, near infrared spectroscopy combined with machine learning algorithms can quickly predict the potential risks of clinical use of Reduning Injection in batches. Three key quality parameters that may affect clinical safety were identified by TreeNet, which provided a scientific basis for improving the safety standards of Reduning Injection.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Machine Learning ; Algorithms ; Humans ; Quality Control

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.
Humans ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child, Preschool ; Transplantation, Homologous ; Child ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins, Fusion/genetics*

OBJECTIVE: To explore the diagnostic value of shear wave elastography (SWE) for clinically significant prostate cancer (csPCa). METHODS: We retrospectively analyzed the clinical data of 359 cases with suspected prostate cancer (PCa) in Baoji Central Hospital from June 2017 to July 2023. All the patients underwent the following examinations in the order of serum prostate-specific antigen (PSA) testing, transrectal ultrasonography (TRUS), measurement of the stiffness of the entire prostate gland by SWE, and TRUS-guided prostate puncture biopsy. The stiffness of the entire prostate gland was defined as the average of Young's modulus at both sides of the base, middle, and apex of the prostate, including the maximum Young's modulus (Emax), mean Young's modulus (Emean), and minimum Young's modulus (Emin). We analyzed the correlation of the parameters of the stiffness of the entire prostate gland with the pathological results, focusing on their diagnostic performance for csPCa. RESULTS: Of the 359 cases, 189 were diagnosed by pathological puncture biopsy as BPH, 26 as non-csPCa, and 144 as csPCa. The PSA level, Emax, Emean and Emin were significantly higher in the csPCa than those in the BPH and non-csPCa groups (all P < 0.01), but showed no statistically significant difference between the BPH and non-csPCa groups (all P > 0.05). The area under the receiver operating characteristic curve (AUC), optimal cut-off value, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of Emax in the diagnosis of csPCa were 0.852, 143.92 kPa, 72.22%, 84.65%, 75.91%, 81.98% and 79.67%; those of Emean were 0.868, 82.42 kPa, 67.36%, 91.16%, 83.62%, 80.66% and 81.62%; and those of Emin were 0.682, 32.73 kPa, 47.22%, 89.30%, 73.91%, 71.54% and 72.14%, respectively. In the non-csPCa group, Emax, Emean and Emin were found below the optimal cut-off value in 73.08% (19/26), 92.31% (24/26) and 88.46% (23/26), respectively. CONCLUSION The stiffness of the entire prostate gland measured by SWE contributes to the diagnosis of csPCa, reduces unnecessary detection of non-csPCa, and provides some reference for its active surveillance.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Elasticity Imaging Techniques ; Retrospective Studies ; Prostate/pathology* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

Objective: To evaluate the therapeutic potential and underlying mechanisms of action of propolis in db/db mice. Methods: The chemical composition of propolis was analyzed using UHPLC-MS/MS. Thirty mice, including six wt/wt and 24 db/db mice, were randomly assigned to four groups (n = 6 per group): control, model, metformin (250 mg/kg), low dose propolis (100 mg/kg), and high dose propolis (HDP; 400 mg/kg). Treatments were administered orally for four weeks. Body weight and FBG levels were recorded weekly, and an oral glucose tolerance test was conducted on the 25th day. Serum levels of FIN, GSP, connecting peptide, AST, ALT, HDL, LDL, TG, and TC were quantified using ELISA. Liver histopathology was assessed using H&E and PAS staining. Western blotting was performed to examine the expression levels of NF-κB, phosphorylated NF-κB, IκBα, pIκBα, and AKT in liver tissues. Results: The top 10 metabolites of propolis were identified in positive and negative ion modes. The HDP group exhibited a significant reduction in FBG levels, body weight, connecting peptide levels, homeostatic model assessment of β-cell function scores, and homeostasis model assessment of insulin resistance scores (all P < .05). GSP levels were significantly reduced in both treatment groups (all P < .001). The HDP group also exhibited a reduction in TC and LDL levels (both P < .05), whereas HDL levels increased in both treatment groups (all P < .05). Liver weight, AST levels, and ALT levels were reduced in both treatment groups (all P < .05). Histological analysis revealed improved liver morphology. Protein analysis demonstrated downregulation of phosphorylated NF-κB and phosphorylated IκB, alongside upregulation of AKT. Conclusion Propolis exhibited significant antihyperglycemic effects in db/db mice, potentially by modulating the AKT and NF-κB signaling pathways, highlighting its potential as a therapeutic agent for diabetes management.

Objective:To explore the mechanism of long non-coding RNA RP11-79H23.3 in the development and progression of prostate cancer.Methods:The lnCAR database was used to analyze the RP11-79H23.3 content in prostate cancer tissues and adjacent tissues. RP11-79H23.3 content in prostate cancer cell lines C4-2B, LNCaP, DU-145, and 22Rv1 was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Taking 22Rv1 as the research target, colony formation experiments and scratch experiments were used to detect the effects of overexpression of RP11-79H23.3 on the proliferation and migration of 22Rv1 cells. The LncRNome and lncACTdb databases were used to predict the downstream gene and binding sequences of RP11-79H23.3. The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between RP11-79H23.3 and miR-410 expression in prostate cancer tissues. The binding of RP11-79H23.3 and miR-410 was confirmed by dual-luciferase reporter gene experiment. The effect of RP11-79H23.3 on the expression of miR-410 was detected by RT-qPCR. Western blotting was used to detect the effect of RP11-79H23.3 on the expression of phosphatase and tensin homolog/protein kinase B/mammalian target of rapamycin (PTEN/AKT/mTOR) signaling pathway proteins in 22Rv1 cells. The measurement data were expressed as mean ± standard deviation ( ± s), paired sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with adjacent tissues, RP11-79H23.3 was lowly expressed in prostate cancer tissues ( P<0.01). Compared with normal prostate epithelial cells RWPE-1, RP11-79H23.3 was lowly expressed in prostate cancer cell lines C4-2B, LNCaP, DU-145, and 22Rv1 ( P<0.05). The expression of RP11-79H23.3 in 22Rv1 cells in the control group and RP11-79H23.3 group were 1.02 ± 0.30 and 8.94±1.95, respectively. 22Rv1 cells were successfully overexpressed RP11-79H23.3 compared with the control group ( t=4.04, P<0.01). The number of 22Rv1 cell clones in the control group and RP11-79H23.3 group were 166.10 ± 18.35 and 35.03±6.98, respectively. Overexpression of RP11-79H23.3 could inhibit the proliferation of 22Rv1 cells compared with the control group ( t=6.67, P<0.01). The migration rates of 22Rv1 cells in the control group and RP11-79H23.3 group were (67.40 ± 6.29)% and (26.42 ± 6.24)%, respectively. Overexpression of RP11-79H23.3 could inhibit the migration of 22Rv1 cells compared with the control group ( t=5.71, P<0.01) .Dual-luciferase reporter gene experiment showed that RP11-79H23.3 directly binds to miR-410 ( t=6.20, P<0.01). The expression of miR-410 in 22Rv1 cells in the control group and RP11-79H23.3 group were 6.22±1.39 and 1.05±0.23, respectively. RP11-79H23.3 could inhibit the expression of miR-410 in 22Rv1 cells compared with the control group ( t=3.68, P<0.01). At the same time, RP11-79H23.3 can inhibit the transduction of the PTEN/AKT/mTOR signaling pathway in 22Rv1 cells. Conclusion:RP11-79H23.3 blocks the PTEN/AKT/mTOR signaling pathway by inhibiting the expression of miR-410, thereby inhibiting the proliferation and migration of prostate cancer 22Rv1 cells.