Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Objective To investigate the neuroprotective effect of Dendrobium nobile Lindl(DNL)extract in a Caenorhabditis elegans(C.elegans)model of Parkinson's disease(PD).Methods C.elegans NL5901 and 6-hydroxydopamine(6-OHDA)induced N2,BZ555,PD4521,and CB7272 C.elegans strains were treated with DNL 7.5,15,and 30 mg/L.The survival rate,basal slowing response rate,α-synuclein(α-syn)aggregation,dopaminergic neurons(DNs),mitochondrial distribution density of body wall muscle cells,and protein levels in the membrane were observed.In addition,reactive oxygen species(ROS),superoxide dismutase(SOD)and glutathione(GSH)in 6-OHDA induced N2 was detected to explore the effect of DNL on the antioxidative stress ability of PD C.elegans models.Results Compared with that in the model group,the DN fluorescence intensity was significantly increased in nematodes treated with DNL and levodopa(L-DOPA)(P＜0.05,P＜0.0001),α-syn aggregation was significantly decreased(P＜0.05,P＜0.001,P＜0.0001),the basal slowing rate(P＜0.05,P＜0.01,P＜0.001),mitochondrial density(P＜0.05,P＜0.01,P＜0.001),mitochondrial intima protein content(P＜0.05,P＜0.001,P＜0.0001),SOD content(P＜0.05),and GSH content were all increased.The ROS content was reduced in nematodes(P＜0.01).The lifespans of N2 wild-type and PD C.elegans models were prolonged after DNL treatment(P＜0.05,P＜0.01,P＜0.001).Conclusions DNL can effectively improve motor paralysis in a C.elegans PD model,improve DN degradation,inhibit α-syn aggregation and neuronal damage,increase the antioxidative stress ability,and slow the aging process in C.elegans.

Early neurological deterioration(END)occurs in patients with acute cerebral infarction after recombinant tissue-plasminogen activator(rt-PA)intravenous thrombolysis,which seriously affects the prognosis of patients and even causes death.However,there is no effective treatment.This report describes two patients with acute ischemic stroke presenting with right-sided limb weakness within 4.5 hours of onset.Brain CT ruled out cerebral hemorrhage and both patients were diagnosed with acute ischemic stroke.END occurred within 24 hours after intravenous thrombolysis with rt-PA.Reexamine Brain CT showed no evidence of cerebral hemorrhage.The patients were treated with continuous tirofiban infusion for 48 hours,overlapping with oral antiplatelet therapy for 4 hours and 6 hours,respectively.After discontinuation of tirofiban,no further neurological deterioration was observed.At the 3-month follow-up,there was no recurrence,and the modified Rankin scale(mRS)scores were 1 and 3,respectively.This study delineates the diagnostic and therapeutic trajectories of two paradigmatic cases to inform clinical decision-making for analogous presentations,thereby contributing to evidence-based management strategies.

Objective To investigate the neuroprotective effect of Dendrobium nobile Lindl(DNL)extract in a Caenorhabditis elegans(C.elegans)model of Parkinson's disease(PD).Methods C.elegans NL5901 and 6-hydroxydopamine(6-OHDA)induced N2,BZ555,PD4521,and CB7272 C.elegans strains were treated with DNL 7.5,15,and 30 mg/L.The survival rate,basal slowing response rate,α-synuclein(α-syn)aggregation,dopaminergic neurons(DNs),mitochondrial distribution density of body wall muscle cells,and protein levels in the membrane were observed.In addition,reactive oxygen species(ROS),superoxide dismutase(SOD)and glutathione(GSH)in 6-OHDA induced N2 was detected to explore the effect of DNL on the antioxidative stress ability of PD C.elegans models.Results Compared with that in the model group,the DN fluorescence intensity was significantly increased in nematodes treated with DNL and levodopa(L-DOPA)(P＜0.05,P＜0.0001),α-syn aggregation was significantly decreased(P＜0.05,P＜0.001,P＜0.0001),the basal slowing rate(P＜0.05,P＜0.01,P＜0.001),mitochondrial density(P＜0.05,P＜0.01,P＜0.001),mitochondrial intima protein content(P＜0.05,P＜0.001,P＜0.0001),SOD content(P＜0.05),and GSH content were all increased.The ROS content was reduced in nematodes(P＜0.01).The lifespans of N2 wild-type and PD C.elegans models were prolonged after DNL treatment(P＜0.05,P＜0.01,P＜0.001).Conclusions DNL can effectively improve motor paralysis in a C.elegans PD model,improve DN degradation,inhibit α-syn aggregation and neuronal damage,increase the antioxidative stress ability,and slow the aging process in C.elegans.

Objective In this study,we aimed to use network pharmacology techniques to predict the key targets of a prescription of Ziziphi spinosae semen formula(ZSSF)compound for depression,and to verify its mechanism of action using a zebrafish model of rifampicin-induced depression.Methods The drug targets of ZSSF were retrieved from the TCMSP database,and the target names were corrected using the UniProt database.Depression-related targets were identified using the GeneCards,OMIM,and NCBI databases.Protein-protein interaction information for the shared targets was predicted using the STRING database.The collected data were then analyzed using the Metascape database to determine GO and KEGG pathway enrichment,and the result were visualized using microbiotics.Behavioral experiments and reverse-transcription quantitative PCR experiments were conducted to verify the therapeutic effects of ZSSF on a zebrafish depression model induced by risperdal.Results 188 targets were screened to find the interactions between depression and ZSSF.The protein-protein interaction result showed that ZSSF primarily targeted TNF-α,IL-2,IL-6,IL-1β,and IL-10 to produce its antidepressant effect.KEGG pathway enrichment analysis revealed that ZSSF exerted its effects on depression through various signaling pathways,including the TNF,PI3K-Akt,and cGMP-PKG signaling pathways.The result of the animal experiments showed that the treatment groups given high,medium,and low doses of ZSSF exhibited significant improvements in movement distance under acoustic and light stimulation compared with the model group(P＜0.05).The speed of movement of the treatment groups was also significantly faster(P＜0.01).Additionally,the mRNA expression levels of TNF-α,IL-2,IL-6,IL-1β,and IL-10 were up-regulated in the brain tissues of zebrafish in the high-,medium-,and low-dosage groups of ZSSF compared those in the model group(P＜0.001).Conclusions ZSSF exerts its antidepressant effect through multiple components and targets,and its antidepressant effects may be associated with its inhibition of inflammatory factors.

Objective To investigate the effects of alcoholic extract of Hemerocallis citrina Baroni on the depressive-like behaviors in zebrafish larvae(Danio rerio)induced by reserpine.Methods Zebrafish larvae were divided into various groups:control(Con)group,reserpine group,fluoxetine group,H.citrina alcohol extract(HCE)low dose group(1.5 mg/L),HCE medium dose group(3 mg/L),and HCE high dose group(4.5 mg/L).Depressive-like behaviors were analyzed using sound and light stimulation.Real-time PCR was used to investigate the effects of HCE on depression related astrocyte markers(GFAP,C3,C4B,EMP-1,S100α-10)and the neurotrophic factor BDNF and its receptor genes(P75,TrkB).Results In comparison to the control group,the model group demonstrated significantly shorter movement distance and reduced movement time under sound and light stimulation(P＜0.05,P＜0.001,P＜0.0001).Following the administration of HCE,zebrafish larvae exhibited significantly heightened sensitivity to light and sound stimulation compared to the model group(P＜0.05,P＜0.0001).Astrocyte marker genes were up-regulated in the model group zebrafish brains compared to the control group(P＜0.0001).However,when the model group was administered HCE,the expression of astrocyte markers was significantly down-regulated compared to the model group(P＜0.0001).Neurotrophic factor and its receptor genes(BDNF,P75,TrkB)were down-regulated in zebrafish brains in the model group compared to those in the control group(P＜0.0001).However,in the group administered HCE,the expression of BDNF,P75,and TrkB was significantly up-regulated compared to that in the model group(P＜0.01,P＜0.0001).These findings suggest that HCE suppressed the inflammatory responses caused by astrocyte activation and promoted the production of neurotrophic factors and their receptor genes,thereby exerting an ameliorative effect on depression.Conclusions Alcoholic extracts of H.citrina can ameliorate the depression-like behavioral changes induced by reserpine in zebrafish larvae.They reduce the expression of astrocyte markers in the zebrafish brain and promote the production of neurotrophic factors and their receptor genes,playing an antidepressant role.

Objective To examine the hypoglycemic effect of Chinese yam polysaccharide on the 3T3-L1 insulin resistance cell model.Methods IR-3T3-L1 adipocytes were randomly divided into control group(Con),model group(DEX),metformin group(Met,positive drug group)and CYPS group(0.05,0.15,0.45 mg/mL).After the creation of the IR-3T3-L1 cell model by dexamethasone(DEX)(1 μmol/L)stimulation,Chinese yam polysaccharide treatment was applied.Glucose intake and the levels of TC,TG,LDL-C,HDL-C,GSH-Px,MDA,HK,and PK were then measured.AMPK-PI3K/Akt signaling pathway-associated gene expression was identified using qRT-PCR.Results The glucose consumption of IR-3T3-L1 cells was considerably decreased after 48 hours of treatment with 1 μmol/L DEX compared to that of the Con group(P＜0.01),and the reduction persisted for 60 hours.0.05,0.15,0.45 mg/mL CYPS treatment significantly increased glucose consumption(P＜0.01),HK,PK,GSH-Px enzyme activities(P＜0.01),HDL-C content(P＜0.01),and decreased MDA enzyme activity(P＜0.01),T-CHO,TG,LDL-C content(P＜0.01)in IR-3T3-L1 cells.01).Additionally,CYPS administration dramatically decreased PI3K,Akt,GLUT-4,AMPK,IRS-2,PPARa,and adiponectin mRNA expression levels(P＜0.05)and reduced IRS-1,GSK-3β,ACC,and FAS mRNA expression levels(P＜0.01).Conclusions In IR-3T3-L1 cells,CYPS can reduce oxidative stress,control lipid metabolism disorders,and enhance DEX-induced glucose intake.AMPK-PI3K/Akt signaling pathway-associated genes may be connected to the process.

Objective:To investigate the clinical efficacy of femoral component revision surgery in addressing polyethylene sleeve wear in rotating hinge knee joints.Methods:A retrospective analysis was conducted on 21 patients who underwent treatment for polyethylene sleeve wear in rotating hinge knee joints at the Department of Orthopaedics, the Fourth Medical Center, PLA General Hospital, spanning from August 2008 to April 2023. There were 8 males and 13 females with a median age of 63(38, 76) years. Among them, 11 cases involved the left side, and 10 cases involved the right side. The average body mass index (BMI) was 25.0(22.5, 31.0) kg/m 2, and all cases underwent unilateral knee joint revision. The time interval from receiving the hinge knee joint prosthesis to revision was 10.5(6.0, 17.0) years, with 18 cases undergoing primary revision and 3 cases undergoing revision for the second time. Revision surgery of the femoral component sleeve was performed in all patients due to polyethylene sleeve wear. Visual analogue scale (VAS), range of motion (ROM) of the knee joint, changes in hip-knee-ankle angle (HKA), and Knee Society score (KSS) were collected and recorded to assess the surgical outcomes. Results:All patients were followed up for a median duration of 12.5(11.7, 13.4) months. Preoperatively, the VAS score was 5(3, 7) points, which significantly decreased to 0(0, 1) points at the last follow-up ( Z=5.721, P<0.001). At the last follow-up, the KSS scores decreased from 41.19±13.65 points preoperatively to 79.81±7.80 points, indicating a statistically significant difference ( t=12.560, P<0.001). HKA increased from 174.65°±5.20° preoperatively to 178.71°±2.79°, with a statistically significant difference ( t=5.533, P<0.001). Knee joint ROM increased from 69.05°±34.37° preoperatively to 110.00°±10.12°, also demonstrating a significant improvement ( t=5.960, P<0.001). Notably, patients exhibited knee joint stability with no passive flexion or extension laxity. Conclusion:Femoral component sleeve revision surgery effectively addresses polyethylene sleeve wear in rotating hinge knee joint prostheses, thereby mitigating the substantial loss of bone and soft tissue associated with overall revision procedures. The early postoperative clinical outcomes are promising and indicative of the efficacy of this surgical intervention.

Objective: To investigate the mechanism of miR-31-5p/tension protein 1 gene (TNS1) axis modulating radiotherapy resistance in breast cancer. Methods: The breast cancer tissues and corresponding para-cancerous tissues of 21 patients with breast cancer, who underwent surgical resection at Department of Cancer Radiotherapy of Nanyang Central Hospital from July 2017 to December 2017, were collected for this study; breast cancer cell lines (MCF-7，MDA-MB-23 and SKBR-3) were also collected; qPCR was applied to detect the expression level of miR-31-5p in breast cancer tissues and cell lines. The radiation resistant cell line MCF-7R was constructed by using 6 MV-X ray radiotherapy treatment. Subsequently, the influence of over-expression/kockdown of miR-31-5p on radiation sensitivity of MCF-7 and MCF-7R cells were detected by colony formation assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Moreover, luciferase reporter assay was used to verify whether TNS1 was a target gene of miR-31-5p. Results: Compared with para-cancerous tissues, normal mammary epithelial MCF-10A cells and MCF-7 cells, miR-31-5p was low-expressed in breast cancer, cell lines and MCF-7R (all P<0.01). Over-expression of miR-31-5p resulted in inhibited invasion and promoted apoptosis of MCF-7R cells (P<0.01), whereas miR-31-5p knockdown got opposite results in MCF-7 cells. Moreover, luciferase reporter assay confirmed that TNS1 was a target gene of miR-31-5p. Over-expression of miR-31-5p inhibited invasion and increased radio-sensitivity, apoptosis of MCF-7R cell via targeting TNS1 (P<0.01), whereas knockdown of miR-31-5p significantly promoted the invasion but reduced apoptosis of MCF-7R cells (all P<0.01), and further up-regulated the radio-sensitivity of MCF-7R cells. Conclusion: miR-31-5p/TNS1 axis regulates the radiotherapy resistance of breast cancer, and over-expression of miR-31-5p may reverse the resistance of MCF-7R to radiotherapy.