ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

Coronary microcirculation disorder after myocardial ischemia reperfusion （MIR） is a prominent problem in the treatment of coronary heart disease. According to the physiological commonality between “collaterals-sweat pore qi and fluid” and coronary microcirculation， and the evolution of the course of MIR， it is believed that “heart collateral stasis obstruction， sweat pore constraint and block” is the cause of coronary microcirculation disorder. The evolution of the pathogenesis can be divided into three periods. During the myocardial ischemia period， the pathogenesis is heart collaterals obstruction and sweat pores empty， while during the ischemia reperfusion period， it is internal formulation of deficiency wind， spasms of collaterals or slight heart collaterals obstruction； in the coronary microcirculation disorder period， sweat pores constraint and block， constraint transforming into heat， qi and fluid failing to diffuse are the pathogenesis. The corresponding treatment principle is assisting dredge with supplementation， and supplementing deficiency to dispel stasis； treating wind and blood simultaneously， and extinguishing wind to arrest convulsion； clearing heat and cooling blood， and diffusing qi and unblocking qi and fluid. Moreover， it is recommended to treat the heart and lungs simultaneously， and regulate the heart and liver at the same time.

Regulated cell death (RCD), including apoptosis, pyroptosis, necroptosis, and ferroptosis, is regulated by a series of evolutionarily conserved pathways, and is required for development and tissue homeostasis. Based on previous genetic and biochemical explorations of cell death subroutines, the characteristics of each are generally considered distinctive. However, recent in-depth studies noted the presence of crosstalk between the different forms of RCD; hence, the concept of PANoptosis appeared. Cancer, a complex genetic disease, is characterized by stepwise deregulation of cell apoptosis and proliferation, with significant morbidity and mortality globally. At present, studies on the different RCD pathways, as well as the intricate relationships between different cell death subroutines, mainly focus on infectious diseases, and their roles in cancer remain unclear. As cancers are characterized by dysregulated cell death and inflammatory responses, most current treatment strategies aim to selectively induce cell death via different RCD pathways in cancer cells. In this review, we describe five types of RCD pathways in detail with respect to tumorigenesis and cancer progression. The potential value of some of these key effector molecules in tumor diagnosis and therapeutic response has also been raised. We then review and highlight recent progress in cancer treatment based on PANoptosis and ferroptosis induced by small-molecule compounds, immune checkpoint inhibitors, and nanoparticles. Together, these findings may provide meaningful evidence to fill in the gaps between cancer pathogenesis and RCD pathways to develop better cancer therapeutic strategies.

OBJECTIVE: To investigate the serum levels of microRNA-155 (miR-155) and interleukin-6 (IL-6) in uremic dialysis patients and to evaluate the effect of alprostadil (A) on them.
 METHODS: A total of 81 chronic kidney disease (CKD) uremic patients were divided into 4 groups: the peritoneal dialysis group (PD group, n=20), the peritoneal dialysis plus alprostadil group (PD+A group, n=20), the hemodialysis group (HD group, n=21), the hemodialysis plus alprostadil group (HD+A group, n=20). Sixteen healthy people were taken as the normal control (NC) group. The peripheral blood of all objects were collected for serum preparation. The expression of miRNA-155 was determined by real-time qPCR and the serum level of IL-6 was measured by ELISA. Experimental and clinical data of all the objects were collected.
 RESULTS: Serum levels of miRNA-155 and IL-6 were increased in all dialysis patients groups compared with NC group (P<0.05); miRNA-155 expression in PD+A group was down-regulated compared with PD group or HD group (P<0.05); the levels of IL-6 in PD+A and HD+A group were significantly decreased compared with PD group or HD group (P<0.05). Correlation analysis showed that serum level of miR-155 was positively correlated with the level of IL-6 as well as high-sensitivity C-reactive protein (hs-CRP), while miR-155 was negatively correlated with HDL and albumin (P<0.01). Linear stepwise regression analysis indicated that serum miR-155 was independently associated with albumin and hs-CRP.
 CONCLUSION Serum miRNA-155 and IL-6 in uremic dialysis patients were remarkably increased compared to healthy objects. Serum miRNA-155 was positively correlated with the level of IL-6 as well as hs-CRP, while miR-155 was negatively correlated with HDL and albumin. Alprostadil could ameliorate the inflammatory conditions of uremic dialysis patients by inhibition of the IL-6 expression. Serum miRNA-155 may be a novel target for the treatment of uremic dialysis patients.
Alprostadil ; therapeutic use ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Humans ; Interleukin-6 ; blood ; MicroRNAs ; blood ; Peritoneal Dialysis ; Regression Analysis ; Renal Dialysis ; Renal Insufficiency, Chronic ; therapy ; Uremia ; blood ; drug therapy

ObjectiveTo investigate the efficacy of different methods of anesthesia for laparoscopic hysterectomy.MethodsSixty ASA Ⅰ or Ⅱ patients,aged 45-60 yr,weighing 55-65 kg,scheduled for laparoscopic hysterectomy,were equally and randomly divided into 2 groups:combined intravenous-inhalational anesthesia group (group Ⅰ ) and combined spinal-epidoral anesthesia (CSEA) + general anesthesia group (group Ⅱ ).In group Ⅰ,anesthesia was maintained with inhalation of sevoflurane and infusion of remifentanil after induction of anesthesia.In group Ⅱ,CSEA was performed,after the upper level of sensory block was stable,general anesthesia was induced and maintained with inhalation of sevoflurane,and state entropy (SE) was naintained at 45-60.Arterial blood samples were taken to determine the plasma concentrations of adrenaline ( AE ),norepinephrine (NE) and dopamine (DA) after admission to the operation room,after completion of pneumoperitoneum,at 10 min after pneumopentoneum,during uterus traction,during removal of the laryngeal mask airway,and at 10 min after removal of the laryngeal mask airway (T0-5).The time for recovery of spontaneous breathing,extubation time,and time of regaining consciousness were recorded at the end of operation.The side-effects and number of patients requiring increments of analgesics were also recorded within 48 h after operation.Patient' s satisfaction was recorded at 48 h after operation.ResultsCompared with group Ⅰ,the plasma concentrations of AE and NE at T3-5 and the plasma concentrations of DA at T3,5 were significantly decreased,the time for recovery of spontaneous breathing,extubation time,and time of regaining corsciousess were significantly shortened,and the incidence of agitation and the number of patients requiring increments of analgesics were significantly decreased in group Ⅱ ( P ＜0.05).There was no significant difference in the incidence of intraoperative awareness,and nausea and vomiting after operation,and the level of patient' s satisfaction at 48 h after operation between the two groups ( P ＞ 0.05).ConctusionCSEA + general anesthesia has better efficacy than combined intravenous-inhalational anesthesia when used for laparoscopic hysterectomy.