Objective To establish a human luminal breast cancer stem cell(BCSC)model and investigate the inhibitory effects of astragaloside Ⅳ(AS-Ⅳ)on BCSC growth.Methods MCF-7 breast cancer cells were cultured in stem cell-specific medium to induce BCSC formation.The BCSCs were then divided into a blank control group and an AS-Ⅳ treatment group,both groups were given PBS or AS-Ⅳ treatment.Morphological changes were observed after intervention.The therapeutic efficacy of AS-Ⅳ was evaluated using 3D spheroid formation and cell viability assays.Transcriptomic profiling and gene expression analysis were performed to elucidate the underlying mechanisms.Results Compared with the MCF7 breast cancer cells,MCF7 breast cancer stem cell mammospheres exhibited accelerated growth(P＜0.01)and significantly increased expression of the stemness marker ALDH1A1(P＜0.01).Further comparison with the blank control group revealed that astragaloside Ⅳ(AS-Ⅳ)treatment significantly inhibited MCF7 breast cancer stem cell proliferation(P＜0.001)and slowed mammosphere growth(P＜0.01).Transcriptomic analysis demonstrated that differentially expressed genes(DEGs)induced by stem cell modeling and AS-Ⅳ intervention were enriched in the cellular senescence signaling pathway.AS-Ⅳ intervention substantially increased the number of SA-β-gal-positive cells(P＜0.01).RT-PCR analysis confirmed that AS-Ⅳsignificantly upregulated mRNA expression of IL-1α(P＜0.01),P21(P＜0.001),and P53(P＜0.05)in MCF7 breast cancer stem cells.Conclusion Astragaloside Ⅳ suppresses the growth of human luminal breast cancer stem cells by inducing cellular senescence.

OBJECTIVE: To evaluate the analgesic efficacy of ultrasound-guided high fascia iliaca compartment block (HFICB) in managing tourniquet-related pain following total knee arthroplasty (TKA). METHODS: A prospective randomized controlled trial was conducted involving 84 patients with severe knee osteoarthritis or rheumatoid arthritis who underwent unilateral TKA between March 2024 and December 2024. Patients were randomly assigned to two groups ( n=42) using a random number table. In the trial group, ultrasound-guided HFICB was performed preoperatively, with 0.2% ropivacaine injected into the fascia iliaca compartment. No intervention was administered in the control group. Baseline characteristics, including gender, age, surgical side, body mass index, and preoperative visual analogue scale (VAS) scores at rest and during movement, showed no significant difference between the two groups ( P>0.05). In both groups, a tourniquet was applied after osteotomy and before pulsed lavage, and removed after the closure of the first layer of the joint capsule. Postoperative assessments were conducted at 6, 12, 24, and 48 hours, including VAS scores at the tourniquet site (at rest and during movement), Bromage motor block scores, Ramsay sedation scores, and Bruggrmann comfort scale (BCS) scores to evaluate patient comfort. Additionally, the average tramadol consumption and incidence of nausea and vomiting within 48 hours postoperatively were recorded and compared. RESULTS: In the trial group and control group, VAS scores during movement at the tourniquet site significantly improved at all postoperative time points compared to preoperative levels ( P<0.05). VAS scores at rest increased transiently at 6 hours after operation in both groups, and then gradually decreased to the preoperative level. Except that there was no significant difference at 48 hours after operation in the trial group ( P>0.05), there were significant differences at other time points of two groups compared to preoperative score ( P<0.05). Except for VAS score at rest at 6 hours, VAS score during movement at 48 hours, and BCS comfort score at 48 hours ( P>0.05), the trial group showed significantly better outcomes than the control group in terms of VAS score at rest, VAS score during movement, Ramsay sedation scores, and BCS comfort scores at all other time points ( P<0.05). No significant difference was found in Bromage motor block scores between the groups ( P>0.05). Tramadol was used in 3 patients in the trial group and 7 patients in the control group within 48 hours after operation, the dosage was (133.30±14.19) mg and (172.40±22.29) mg, showing significant difference ( P<0.05). Nausea and vomiting occurred in 4 patients (9.5%) in the trial group and 3 patients (7.1%) in the control group, with no significant difference in incidence between groups ( P>0.05). CONCLUSION Ultrasound-guided HFICB provides effective analgesia for tourniquet-related pain following TKA, facilitates early postoperative functional recovery of the knee joint, and may serve as a valuable clinical option for postoperative pain management in TKA patients.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Nerve Block/methods* ; Male ; Female ; Pain, Postoperative/etiology* ; Tourniquets/adverse effects* ; Prospective Studies ; Middle Aged ; Ropivacaine/administration & dosage* ; Aged ; Ultrasonography, Interventional ; Anesthetics, Local/administration & dosage* ; Pain Measurement ; Fascia ; Osteoarthritis, Knee/surgery* ; Treatment Outcome ; Arthritis, Rheumatoid/surgery*

Based on the theory of "three regions and sanjiao" in traditional Chinese medicine (TCM), the acupuncture-moxibustion differentiation and treatment system is explored and constructed for spasm syndrome, so as to provide a clearer guiding framework for TCM treatment of spasm syndrome. This disorder is caused essentially by the invasion of pathogenic wind, and located in brain marrow. The key regions of illness cover five zang organs and five tissues, and the core pathogenesis is associated with wind disturbance in brain marrow. In differentiation, spasm syndrome refers to overall transmission (from the upper to the lower) and local transmission (from exterior to interior). This disorder can be classified into sanjiao spasm (heart-lung spasm of the upper jiao, liver-spleen spasm of the middle jiao, and liver-kidney spasm of the lower jiao) and three-region spasm (skin-vessel spasm of the upper region, tendon-muscle spasm of the middle region, and tendon-bone spasm of the lower region). Based on "three regions and sanjiao" theory of acupuncture and moxibustion, 7 "expelling-wind" points can be selected in terms of the etiology of this disease. Baihui (GV20)-toward-Taiyang (EX-HN5) needling is applied to regulate the brain marrow, focusing on the core location of illness; and regarding the key location of illness, the combination of back-shu and front-mu points and that of jing-well and xing-spring points are adopted to regulate five zang organs. The five needling techniques (half needling, leopard-spot needling, joint needling, Hegu needling and shu needling) are used to regulate five tissues.
Humans ; Acupuncture Therapy ; Spasm/diagnosis* ; Moxibustion ; Acupuncture Points ; Medicine, Chinese Traditional ; Diagnosis, Differential

The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.

Platelet is the key factor in hemostasis and coagulation,its potential in inflammatory response and immune response has been widely concerned in recent years.A growing number of studies indicate that tissue damage in inflammatory bowel disease is not only the result of dysregulated immune response,but also the active participation of various other cellular systems,and platelet might play an important role in intestinal mucosal inflammation and immunity.This article reviewed the abnormal changes and possible mechanisms of platelet in inflammatory bowel disease,and the prospects of platelet as a specific treatment target for inflammatory bowel disease.

Objective:To explore the sequential chemotherapy efficacy of different chemotherapeutic regimens in ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma.Methods:A retrospective analysis was conducted on clinical and pathological data of 100 patients with platinum-sensitive ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma treated at Peking University Peopel′s Hospital from January 1992 to January 2019. All patients underwent staging surgery or cytoreductive surgery followed by adjuvant chemotherapy. Based on different postoperative adjuvant chemotherapy regimens, patients were divided into the sequential chemotherapy group (70 cases) and the conventional chemotherapy group (30 cases). Clinical and pathological characteristics, chemotherapy efficacy, adverse reactions, and prognosis were compared between the two groups.Results:(1) Clinical and pathological characteristics: the age, tumor types (including ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma), pathological types, International Federation of Gynecology and Obstetrics (FIGO) stage, postoperative residual disease size, presence of neoadjuvant chemotherapy, and total number of chemotherapy cycles were compared between the sequential chemotherapy group and the conventional chemotherapy group. There were no statistically significant differences observed in these characteristics between the two groups (all P>0.05). (2) Chemotherapy efficacy: the median sum of complete response (CR)+partial response (PR) duration in the sequential chemotherapy group was 80.0 months (range: 39 to 369 months), whereas in the conventional chemotherapy group, it was 28.0 months (range: 13 to 52 months). A statistically significant difference was observed between the two groups ( Z=-7.82, P<0.001). (3) Chemotherapy adverse reactions: in the sequential chemotherapy group, 55 cases (79%, 55/70) experienced bone marrow suppression and 20 cases (29%, 20/70) had neurological symptoms. In the conventional chemotherapy group, these adverse reactions occurred in 11 cases (37%, 11/30) and 2 cases (7%, 2/30), respectively. Statistically significant differences were observed between the two groups for both bone marrow suppression and neurological symptoms (all P<0.05). For the other chemotherapy adverse reactions compared between the two groups, no statistically significant differences were observed (all P>0.05). (4) Prognosis: during the follow-up period, the recurrence rate in the sequential chemotherapy group was 73% (51/70) and in the conventional chemotherapy group was 100% (30/30). The median sum of recurrence-free interval was 70.5 months (range: 19 to 330 months) in the sequential chemotherapy group and 15.0 months (range: 6 to 40 months) in the conventional chemotherapy group. Statistically significant differences were observed between the two groups for both recurrence rate and median recurrence-free interval (all P<0.01).In the sequential chemotherapy group, the median progression-free survival (PFS) time was 84.0 months (range: 34 to 373 months), and the median overall survival (OS) time was 87.0 months (range: 45 to 377 months). In contrast, in the conventional chemotherapy group, the median PFS time was 30.5 months (range: 14 to 60 months), and the median OS time was 37.5 months (range: 18 to 67 months). Statistically significant differences were observed between the two groups for both PFS and OS (all P<0.001). In the sequential chemotherapy group, the 3-year, 5-year, and 10-year OS rates were 100% (70/70), 93% (65/70), and 21% (15/70), respectively. In contrast, in the conventional chemotherapy group, the OS rates were 50% (15/30) at 3 years, 3% (1/30) at 5 years, and 0 at 10 years, respectively. The two groups were compared respectively, and the differences were statistically significant (all P<0.05). Conclusions:Sequential chemotherapy significantly prolongs PFS and OS in patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma. The efficacy is superior to that of the conventional chemotherapy, with manageable adverse reactions. The use of sequential chemotherapy as first-line treatment for patients with ovarian epithelial carcinoma, fallopian tube carcinoma, and primary peritoneal carcinoma is recommended.

Objective:To summarize and analyze the clinical characteristics, treatment and prognosis of glycogen storage disease type Ⅱ(GSD Ⅱ) patients admitted to pediatric intensive care units(PICU), and to improve the pediatricians' understanding of children with severe GSD Ⅱ.Methods:Children with GSD Ⅱ admitted to PICU at Beijing Children's Hospital of Capital Medical University between January 2010 and December 2021 were included. Patient's data were collected through the electronic medical record system.After the patient was discharged,telephone follow-ups were conducted regularly for over a year.Results:A total of eight patients with a median age of 30.5 months were included. There were four patients with infantile GSD Ⅱ, whose median age of onset was 5.5 months. There were four patients with late-onset GSD Ⅱ, whose median age of onset was 36.0 months. Eight patients required continuous noninvasive/invasive respiratory support. Three patients with infantile GSD Ⅱ required respiratory support within one month of onset, and three patients with late onset GSD Ⅱ required respiratory support within one year of onset. A total of six patients had cardiac arrest during the course of the disease. One patient was regularly treated with enzyme replacement therapy during hospitalization but his condition did not improve significantly. Three patients were discharged following medical advice,including one patient continuing noninvasive respiratory support after discharge, and two patients requiring onging invasive respiratory support.A total of four children died,including one being an in-hospital death,and three occuring within one year after hospital discharge. A total of 14 genotypes were detected in eight patients, of which three were newly discovered gene mutations.Conclusion:The children with GSD Ⅱ admitted to PICU have severe respiratory dysfunction and need continuous respiratory support during the early stage of the disease. The incidence of cardiopulmonary arrest caused by infection and respiratory muscle weakness is high. It is recommended to closely monitor the lung function and cardiac function of such children, and actively give the prevention and treatment of infectious diseases. Whether enzyme replacement therapy can benefit patients with severe GSD Ⅱ and whether the newly identified mutations correlate with disease severity needs to be further evaluated.

Objective:To explore the mechanism of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease(AD).Methods:The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacology methods,the protein-protein interaction(PPI)network was constructed and the core targets were analyzed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways enriching analysis was performed.The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines(LCL)were constructed and an in vitro cell model of LCL-SKNMC was established.MTT and CCK-8 methods were used to quantify SKNMC/LCL cells,2′,7′-dichlorodihydrofluorescein diacetate(DCFH-DA)probe was used to detect reactive oxygen species(ROS),and immunofluorescence staining was used to detect the generation of Aβ1-42 in a co-cultured model.Western blotting was used to detect protein expression in the co-culture model.The lifespan of N2 nematodes was observed under oxidative stress,normal state,and heat stress;ROS generated by N2 nematodes was detected by DCFH-DA probes.The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay,and Aβ deposition in the pharynx was detected by Thioflavin S staining.Results:Through network pharmacology,15 potential active ingredients and 103 drug-disease targets were identified.PPI analysis showed that the Anemarrhenae Rhizoma might play anti-AD roles through albumin,Akt1,tumor necrosis factor,epidermal growth factor receptor(EGFR),vascular endothelial growth factor A(VEGFA),mammalian target of rapamycin(mTOR),amyloid precursor protein(APP)and other related targets.KEGG analysis showed that the pharmacological effects of Anemarrhenae Rhizoma might involve the biological processes of Alzheimer's disease,endocrine resistance,insulin resistance;and neuroactive ligand-receptor interaction,phosphatidylinositol 3-kinase(PI3K)-Akt signaling pathway,calcium signaling pathway,AGE-RAGE signaling pathway in diabetes complications,neurotrophic factor signaling pathway and others.The in vitro cell experiments showed that Anemarrhenae Rhizoma was able to reduce the production of ROS and Aβ1-42(both P<0.01),inhibit the expression of β-secretase 1(BACE1),APP and Aβ1-42 proteins(all P<0.05),up-regulate the expression of p-PI3K/PI3K,p-AKT/AKT,p-GSK3β/GSK3β in SKNMC cells(all P<0.05).The in vivo studies further confirmed that Anemarrhenae Rhizoma prolonged the lifespan of C.elegans under stress and normal conditions,reduced the accumulation of ROS and the toxicity of Aβ deposition.Conclusion:Anemarrhenae Rhizoma may reduce the production of Aβ in AD and inhibit its induced oxidative stress,which may be achieved by regulating the PI3K/Akt/GSK-3β pathway.

Objective:To explore the mechanism of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease(AD).Methods:The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacology methods,the protein-protein interaction(PPI)network was constructed and the core targets were analyzed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways enriching analysis was performed.The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines(LCL)were constructed and an in vitro cell model of LCL-SKNMC was established.MTT and CCK-8 methods were used to quantify SKNMC/LCL cells,2′,7′-dichlorodihydrofluorescein diacetate(DCFH-DA)probe was used to detect reactive oxygen species(ROS),and immunofluorescence staining was used to detect the generation of Aβ1-42 in a co-cultured model.Western blotting was used to detect protein expression in the co-culture model.The lifespan of N2 nematodes was observed under oxidative stress,normal state,and heat stress;ROS generated by N2 nematodes was detected by DCFH-DA probes.The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay,and Aβ deposition in the pharynx was detected by Thioflavin S staining.Results:Through network pharmacology,15 potential active ingredients and 103 drug-disease targets were identified.PPI analysis showed that the Anemarrhenae Rhizoma might play anti-AD roles through albumin,Akt1,tumor necrosis factor,epidermal growth factor receptor(EGFR),vascular endothelial growth factor A(VEGFA),mammalian target of rapamycin(mTOR),amyloid precursor protein(APP)and other related targets.KEGG analysis showed that the pharmacological effects of Anemarrhenae Rhizoma might involve the biological processes of Alzheimer's disease,endocrine resistance,insulin resistance;and neuroactive ligand-receptor interaction,phosphatidylinositol 3-kinase(PI3K)-Akt signaling pathway,calcium signaling pathway,AGE-RAGE signaling pathway in diabetes complications,neurotrophic factor signaling pathway and others.The in vitro cell experiments showed that Anemarrhenae Rhizoma was able to reduce the production of ROS and Aβ1-42(both P<0.01),inhibit the expression of β-secretase 1(BACE1),APP and Aβ1-42 proteins(all P<0.05),up-regulate the expression of p-PI3K/PI3K,p-AKT/AKT,p-GSK3β/GSK3β in SKNMC cells(all P<0.05).The in vivo studies further confirmed that Anemarrhenae Rhizoma prolonged the lifespan of C.elegans under stress and normal conditions,reduced the accumulation of ROS and the toxicity of Aβ deposition.Conclusion:Anemarrhenae Rhizoma may reduce the production of Aβ in AD and inhibit its induced oxidative stress,which may be achieved by regulating the PI3K/Akt/GSK-3β pathway.

Objective:To explore the mechanism of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease(AD).Methods:The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacology methods,the protein-protein interaction(PPI)network was constructed and the core targets were analyzed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways enriching analysis was performed.The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines(LCL)were constructed and an in vitro cell model of LCL-SKNMC was established.MTT and CCK-8 methods were used to quantify SKNMC/LCL cells,2′,7′-dichlorodihydrofluorescein diacetate(DCFH-DA)probe was used to detect reactive oxygen species(ROS),and immunofluorescence staining was used to detect the generation of Aβ1-42 in a co-cultured model.Western blotting was used to detect protein expression in the co-culture model.The lifespan of N2 nematodes was observed under oxidative stress,normal state,and heat stress;ROS generated by N2 nematodes was detected by DCFH-DA probes.The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay,and Aβ deposition in the pharynx was detected by Thioflavin S staining.Results:Through network pharmacology,15 potential active ingredients and 103 drug-disease targets were identified.PPI analysis showed that the Anemarrhenae Rhizoma might play anti-AD roles through albumin,Akt1,tumor necrosis factor,epidermal growth factor receptor(EGFR),vascular endothelial growth factor A(VEGFA),mammalian target of rapamycin(mTOR),amyloid precursor protein(APP)and other related targets.KEGG analysis showed that the pharmacological effects of Anemarrhenae Rhizoma might involve the biological processes of Alzheimer's disease,endocrine resistance,insulin resistance;and neuroactive ligand-receptor interaction,phosphatidylinositol 3-kinase(PI3K)-Akt signaling pathway,calcium signaling pathway,AGE-RAGE signaling pathway in diabetes complications,neurotrophic factor signaling pathway and others.The in vitro cell experiments showed that Anemarrhenae Rhizoma was able to reduce the production of ROS and Aβ1-42(both P<0.01),inhibit the expression of β-secretase 1(BACE1),APP and Aβ1-42 proteins(all P<0.05),up-regulate the expression of p-PI3K/PI3K,p-AKT/AKT,p-GSK3β/GSK3β in SKNMC cells(all P<0.05).The in vivo studies further confirmed that Anemarrhenae Rhizoma prolonged the lifespan of C.elegans under stress and normal conditions,reduced the accumulation of ROS and the toxicity of Aβ deposition.Conclusion:Anemarrhenae Rhizoma may reduce the production of Aβ in AD and inhibit its induced oxidative stress,which may be achieved by regulating the PI3K/Akt/GSK-3β pathway.