ObjectiveTo explore the potential mechanism underlying electroacupuncture therapy with the midnight-noon ebb-low method with hour-prescription for chronic obstructive pulmonary disease （COPD） with lung-qi deficiency syndrome from the perspective of brain and muscle basic helix-loop-helix ARNT-like 1 （BMAL1） as well as neutrophil extracellular traps （NETs）. MethodsThe experiment was conducted in two phases. For the therapeutic effectiveness observation， 24 rats were randomly allocated into control group 1， model group 1， midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group， with 6 rats per group. Rat models of COPD with lung-qi deficiency syndrome were established via cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide （LPS）. After successful modelling， rats in midnight-noon electro-acupuncture group 1 received electro-acupuncture at acupoints "Taiyuan （LU 9）"， "Feishu （BL 13）" and "Zusanli （ST 36）" during 05：00—07：00， 30 minutes per treatment once every other day for 14 consecutive days （7 sessions in total）. Rats in the conventional electro-acupuncture group received identical electroacupuncture manipulation at random daytime hours （08：00—18：00）. Pulmonary function parameters including forced expiratory volume in 0.3 second （FEV_0.3）， forced vital capacity （FVC） and FEV_0.3/FVC ratio were detected. Pulmonary histopathological changes were observed via hematoxylin-eosin （HE） staining. Plasma levels of pro-inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as pulmonary reactive oxygen species （ROS） content， BMAL1 protein expression and the levels of neutrophil extracellular traps （NETs） biomarkers such as myeloperoxidase （MPO）， neutrophil elastase （NE）， and citrullinated histone H3 （CitH3） in lung tissue were determined. For the mechanistic verification phase， 36 rats were divided into control group 2， model group 2， midnight-noon electro-acupuncture group 2， overexpression empty group， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group， with 6 rats in each group. At the 5th week of model construction， rats in the overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group received intratracheal instillation of 100 μl adenoviral suspension carrying overexpressed Bmal1 gene. Rats in the overexpression empty group were injected with an equal titer and equal volume of blank adenovirus without the Bmal1 coding sequence into the lung at the identical time point. Midnight-noon electro-acupuncture group 2 and overexpression with midnight-noon electro-acupuncture group were consistent with the aforementioned protocol. Finally， pulmonary levels of MPO， NE and CitH3 were measured in all groups. ResultsCompared with the control group 1， the model group 1 exhibited decreased FEV_0.3， FVC and FEV_0.3/FVC ratio， elevated plasma IL-1β， TNF-α and pulmonary ROS levels， downregulated lung BMAL1 protein expression， and increased contents of MPO， NE and CitH3 （all P＜0.05）； typical NETs-like structures with sparse granular substances attached to fibrous networks were observed under scanning electron microscopy； HE staining revealed damaged alveolar architecture accompanied by inflammatory cell infiltration. Compared with model group 1， both the midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group achieved obvious improvements in all above indicators， with superior therapeutic effects in midnight-noon electro-acupuncture group 1 （P＜0.05）. Consistently， midnight-noon electro-acupuncture group 1 showed more prominent alleviation of NETs-like structure formation and lung pathological injury compared to the conventional electro-acupuncture group. Mechanistic validation results demonstrated that compared with model group 2， the average optical density of MPO as well as the protein levels of MPO， NE and CitH3 were markedly reduced in midnight-noon electro-acupuncture group 2， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group （P＜0.05）； furthermore， these parameters were significantly lower in the overexpression with midnight-noon electro-acupuncture group than in midnight-noon electro-acupuncture group 2 （P＜0.05）. ConclusionElectro-acupuncture based on the midnight-noon ebb-low method with hour-prescription may alleviate pulmonary inflammation in COPD by upregulating the expression of clock protein BMAL1 and inhibiting excessive accumulation of NETs in lung tissue.

ObjectiveTo evaluate the clinical efficacy and safety of Wenshen Yangxue decoction combined with endometrial microstimulation in the treatment of infertile patients with polycystic ovary syndrome （PCOS， syndrome of kidney-Yang deficiency and blood stasis）. MethodsA randomized， positive-drug parallel-controlled， open-label clinical study was conducted. A total of 240 infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis who met the inclusion and exclusion criteria were randomly assigned into 4 groups， with 60 patients in each group. The control group was treated with clomiphene citrate （50-100 mg·d^-¹， orally for 5-10 consecutive days） for ovulation induction. On the basis of the therapy in the control group， the Wenshen group was additionally treated with Wenshen Yangxue decoction （250 mL， warm oral administration， twice daily， in the morning and evening）， and the stimulation group received endometrial microstimulation during the early follicular phase. The combined group was treated with clomiphene citrate plus Wenshen Yangxue decoction （at the same dosages as aforementioned） and endometrial microstimulation. The course of treatment for all the groups was 3 menstrual cycles. The pregnancy rate， ovulation status， sex hormone levels， glucose metabolism indicators， coagulation function， endometrial thickness， traditional Chinese medicine （TCM） symptom scores， and adverse reactions were observed in each group. ResultsA total of 239 patients were included in the final analysis， with 59 patients in the Wenshen group and 60 patients in each of the other three groups. The pregnancy rates were 43.3%（26/60） in the combined group and 32.2%（19/60） in the Wenshen group， both significantly higher than that （10%） in the control group （χ²=17.56，P<0.01）. Compared with the control group， the combined and Wenshen groups had increased mature follicle rates （P<0.01）， while the Wenshen group showed a decreased luteinization rate （P<0.05）. All the groups exhibited significant reductions in TCM symptom scores after treatment， and the Wenshen and combined groups had lower scores than the control group （P<0.01）. No statistically significant difference was found in the incidence of adverse events among the four groups， and all the adverse events were mild. ConclusionWenshen Yangxue decoction combined with endometrial microstimulation can alleviate the TCM symptoms of infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis， promote follicular maturation and ovulation， increase the cumulative pregnancy rate， and has good safety. It can provide new clinical evidence for the integrated traditional Chinese and Western medicine treatment of PCOS infertility.

ObjectiveTo evaluate the clinical efficacy and safety of Wenshen Yangxue decoction combined with endometrial microstimulation in the treatment of infertile patients with polycystic ovary syndrome （PCOS， syndrome of kidney-Yang deficiency and blood stasis）. MethodsA randomized， positive-drug parallel-controlled， open-label clinical study was conducted. A total of 240 infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis who met the inclusion and exclusion criteria were randomly assigned into 4 groups， with 60 patients in each group. The control group was treated with clomiphene citrate （50-100 mg·d^-¹， orally for 5-10 consecutive days） for ovulation induction. On the basis of the therapy in the control group， the Wenshen group was additionally treated with Wenshen Yangxue decoction （250 mL， warm oral administration， twice daily， in the morning and evening）， and the stimulation group received endometrial microstimulation during the early follicular phase. The combined group was treated with clomiphene citrate plus Wenshen Yangxue decoction （at the same dosages as aforementioned） and endometrial microstimulation. The course of treatment for all the groups was 3 menstrual cycles. The pregnancy rate， ovulation status， sex hormone levels， glucose metabolism indicators， coagulation function， endometrial thickness， traditional Chinese medicine （TCM） symptom scores， and adverse reactions were observed in each group. ResultsA total of 239 patients were included in the final analysis， with 59 patients in the Wenshen group and 60 patients in each of the other three groups. The pregnancy rates were 43.3%（26/60） in the combined group and 32.2%（19/60） in the Wenshen group， both significantly higher than that （10%） in the control group （χ²=17.56，P<0.01）. Compared with the control group， the combined and Wenshen groups had increased mature follicle rates （P<0.01）， while the Wenshen group showed a decreased luteinization rate （P<0.05）. All the groups exhibited significant reductions in TCM symptom scores after treatment， and the Wenshen and combined groups had lower scores than the control group （P<0.01）. No statistically significant difference was found in the incidence of adverse events among the four groups， and all the adverse events were mild. ConclusionWenshen Yangxue decoction combined with endometrial microstimulation can alleviate the TCM symptoms of infertile PCOS patients with the syndrome of kidney-Yang deficiency and blood stasis， promote follicular maturation and ovulation， increase the cumulative pregnancy rate， and has good safety. It can provide new clinical evidence for the integrated traditional Chinese and Western medicine treatment of PCOS infertility.

OBJECTIVE To investigate the improvement effects of total flavonoids from Bidens pilosa （TFB）against Alzheimer’s disease （AD） and elucidate its potential mechanism. METHODS The network pharmacology was adopted to explore active constituents and core targets of TFB for AD， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Based on the results of network pharmacology， an AD model was induced in male BALB/c mice by D-galactose subcutaneous injection and aluminum chloride gavage. The effects of TFB on behavioral indicators （including escape latency， the number of platform crossings， and the proportion of dwell time spent in the original platform quadrant）， as well as on acetylcholinesterase （AChE）， acetylcholine （ACh）， choline acetyltransferase （ChAT）， amyloid β-protein （Aβ）， phosphorylated Tau protein （p-Tau）， and inflammatory factors [interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α）] were investigated. Additionally， its effects on the pathological changes in hippocampal neurons， as well as the expressions of related proteins and mRNAs were evaluated. RESULTS Network pharmacology revealed 6 active components in TFB （e.g. luteolin， quercetin， kaempferol） and 165 overlapping targets with AD， including 29 core targets （Akt1， TP53， etc.）. The common targets were primarily enriched in biological processes such as positive regulation of gene expression and negative regulation of apoptotic processes， molecular functions including enzyme binding and identical protein binding， cellular components like extracellular space， plasma membrane and receptor complex， as well as signaling pathways such as cancer pathways and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. The results of animal experiments showed that， compared with model group， the pathological changes such as disordered arrangement， degeneration， and necrosis of neurons in the hippocampal CA3 region of mice in administration groups were alleviated. The escape latency （except for the low-dose TFB group）， the contents of AChE （except for the low-dose TFB group）， Aβ40， Aβ42 （except for the low-dose TFB group）， p-Tau （except for the low- and medium-dose TFB groups）， IL-1β， IL-6 （except for the low-dose TFB group）， and TNF- α in brain tissue， as well as the expressions of Bax and caspase-3 mRNA， were all significantly shortened/reduced/down-regulated. Conversely， the number of platform crossings， the proportion of dwell time spent in the original platform quadrant， the contents of ChAT and ACh， the phosphorylation levels of PI3K and Akt， and the mRNA expressions of PI3K， Akt and Bcl-2 （except for PI3K mRNA and Akt mRNA in the low- and medium-dose TFB groups， and Bcl-2 mRNA in the low-dose TFB group） were all significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS TFB can exert anti-AD effect through multiple components， multiple targets， and multiple pathways. Its underlying mechanisms may be related to the activation of the PI3K/Akt signaling pathway， improvement of the cholinergic system， reduction of Aβ deposition and Tau protein hyperphosphorylation， as well as inhibition of neuroinflammatory responses and neuronal apoptosis.

Traditional Chinese medicine(TCM)serves as a treasure trove of ancient knowledge,holding a crucial position in the medical field.However,the exploration of TCM's extensive information has been hindered by challenges related to data standardization,completeness,and accuracy,primarily due to the decen-tralized distribution of TCM resources.To address these issues,we developed a platform for TCM knowledge discovery(TCMKD,https://cbcb.cdutcm.edu.cn/TCMKD/).Seven types of data,including syndromes,formulas,Chinese patent drugs(CPDs),Chinese medicinal materials(CMMs),ingredients,targets,and diseases,were manually proofread and consolidated within TCMKD.To strengthen the integration of TCM with modern medicine,TCMKD employs analytical methods such as TCM data mining,enrichment analysis,and network localization and separation.These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights.In addition to its analytical capabilities,a quick question and answer(Q&A)system is also embedded within TCMKD to query the database efficiently,thereby improving the interactivity of the platform.The platform also provides a TCM text annotation tool,offering a simple and efficient method for TCM text mining.Overall,TCMKD not only has the potential to become a pivotal repository for TCM,delving into the pharmaco-logical foundations of TCM treatments,but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems,extending beyond just TCM.

Postoperative acute pain can significantly hinder early postoperative recovery if inadequately managed,and may even progress to chronic postsurgical pain(CPSP).The current clinical practice primarily relies on multimodal analgesia strategies,with intravenous opioids being the cornerstone.Although effective in alleviating postoperative pain,the associated adverse effects of opioids have limited their widespread use.In recent years,with the development of integrative medicine combining Western and traditional Chinese medicine,numerous studies have demonstrated that incorporating transcutaneous electrical acupoint stimulation(TEAS)into multimodal analgesia protocols confers significant benefits for postoperative pain management.TEAS not only reduces postoperative pain and opioid consumption but also mitigates opioid-related side effects,thereby facilitating patient recovery.This review aims to provide a comprehensive overview of the analgesic mechanisms of TEAS,its application within multimodal analgesia for postoperative pain,and its potential to serve as a valuable reference for clinicians seeking to optimize postoperative pain management strategies.

As the "main force" for providing health services, there has been a constant increase in the number of health service and management graduates in recent years, but with a lack of satisfactory quality. The concept of outcome-based education (OBE) takes the needs of all parties as the starting point and foothold for practice, which can ensure the consistency between the goal of talent training and the learning achievements of students to the greatest extent. This article proposes to integrate the educational concept of OBE into the training path of health service and management talents, clarify talent training objectives by understanding the needs of all parties, optimize the curriculum system according to training objectives, and construct a diversified evaluation system with the organic combination of process evaluation and summative assessment, in order to continuously optimize the training path of health service and management talents and cultivate applied health management talents with knowledge, ability, and quality.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

Corneal neovascularization(CNV)is a pathological condition characterized by the invasion of new blood vessels into the normally avascular corneal area from the corneal periphery,leading to severe vision loss and potentially blindness.Currently,surgical,physical,and pharmacological therapies are the main clinical approaches for treating CNV.Surgical treatment aims to remove abnormal vascular tissue or perform corneal trans-plantation to inhibit angiogenesis;however,it carries a risk of postoperative rejection.Physical therapy involves the direct application of non-invasive modalities,such as laser treatment,to the neovascularized area to suppress vascular growth.Nevertheless,this approach may cause damage to surrounding healthy tissues.Pharmacotherapy has recently become a research hotspot in CNV treatment due to its convenient administration.Clinically,the drugs used for CNV treatment mainly include anti-inflammatory agents,anti-VEGF drugs,and immunosuppressants,which inhibit CNV progression by targeting angiogenesis-related signaling pathways.However,these drugs often lead to drug resistance and toxic side effects.Therefore,there is an urgent need to develop more effective and safer therapeutic agents for CNV.This article reviews the current clinical treatment status of CNV and highlights recent advances in the use of small molecule extracts from traditional Chinese medicine for CNV therapy,aiming to provide potential candidate drugs and a scientific theoretical basis for clinical management of CNV.