Acute ischemic stroke (AIS) is a kind of central nervous system disease that seriously threatens human health and life. Current treatment for AIS is mainly reperfusion. However, the time-sensitive of reperfusion limits its clinical application, and a considerable part of patients within the time window cannot achieve the expected effect after reperfusion; related complications of reperfusion have not been completely solved. So far, some clinical trials have confirmed that neuroprotectants are useful supplements and adjuncts to reperfusion. This paper reviews the recent advance in neuroprotectants combined with reperfusion in AIS to provide references for AIS treatment.

Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator(rt-PA)in the elderly patients(aged over 80 years)with acute ischemic stroke(AIS).Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group(n=93,0.6 mg/kg)and rt-PA standard-dose group(n=108,0.9 mg/kg).The incidence of intra-cranial hemorrhage,symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety.The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness.A stratified analysis of 90-day outcomes was performed based on stroke severity and age.Results The incidence of intracranial hemorrhage,symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group(P＜0.05).There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index.The 90-day good prognosis rate of moderate stroke sub-group and of≥90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group(P＜0.05).Conclusions For AIS patients with moderate stroke and aged over 90 years,intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended.

Objective:To investigate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis combined with edaravone dexborneol at different timing in super elderly patients (aged≥85 years) with moderate to severe acute ischemic stroke (AIS).Methods:A prospective study was performed. Seventy-one super elderly patients with moderate to severe AIS treated with rt-PA intravenous thrombolysis combined with edaravone dexborneol from December 2020 to March 2023 in Department of Neurology, Affiliated Fourth Central Hospital of Nankai University were selected and randomly divided into early group ( n=35) and advanced group ( n=36); patients in the early group were given edaravone dexborneol immediately after rt-PA intravenous thrombolysis, and patients in the advanced group were given edaravone dexborneol 24 h after rt-PA intravenous thrombolysis. In addition, 31 patients with moderate to severe AIS received rt-PA intravenous thrombolysis only in Department of Neurology of the hospital from August 2018 to December 2020 were selected as control group. Differences in efficacy and safety indexes among the 3 groups were compared. Results:After 7 d of treatment, the improvement rate of neurological function in early group was significantly higher than that in control group and advanced group ( P<0.05). After 90 d of treatment, modified Rankin scale (mRS) scores in early group were statistically lower than those in control group and advanced group ( P<0.05); good prognosis rate in early group was statistically higher than that in control group and advanced group ( P<0.05). The incidences of intracranial hemorrhage and symptomatic intracranial hemorrhage in early group were significantly lower than those in control group and advanced group ( P<0.05). After 30 and 90 d of treatment, the advanced group had significantly lower mortality than the control group, but significantly higher mortality than the early group ( P<0.05). Conclusion:Edaravone dexborneol immediately after rt-PA intravenous thrombolysis is the optimal timing for super elderly patients with moderate to severe AIS, which can improve the efficacy and safety.

Objective:To investigate the efficacy and safety of thrombolytic therapy with intravenous alteplase(rt-PA)for elderly acute ischemic stroke patients on maintenance hemodialysis.Methods:In this retrospective study, data of 165 elderly patients with acute cerebral infarction on maintenance dialysis, aged 65-85, treated at the Stroke Center of the Fourth Central Hospital Affiliated to Nankai University between May 2018 and March 2021, were collected.Based on whether intravenous thrombolysis with alteplase(rt-PA)was used and differences in thrombolytic schemes, patients were divided into a conservative treatment group( n=58, receiving only standardized secondary stroke prevention), a low-dose rt-PA group( n=57, receiving rt-PA intravenous thrombolysis, 0.6 mg/kg)and a standard-dose rt-PA group( n=50, receiving rt-PA intravenous thrombolysis, 0.9 mg/kg). The safety and efficacy of rt-PA treatment were assessed. Results:The rate of effectiveness at 24 h and the rate of good prognosis at 7 d were 64.9%(37/57)and 70.2%(40/57)for the low-dose rt-PA group and 68.0%(34/50)and 74.0%(37/50)for the standard dose group, respectively.There was no significant difference between the two groups( χ2=0.417, P=0.518; χ2=0.636, P=0.425), but these rates were better than 29.3%(17/58)and 41.4%(24/58)for the conservative treatment group( χ2=10.583、16.714, P<0.001). The good prognosis rate at 90 days were 73.7%(42/57), 78.0%(39/50)and 69.0%(40/58)for the three groups, respectively, with no significant difference( χ2=1.126, P=0.569), but the fatality rate for the low-dose rt-PA group was 7.0%(4/57), lower than 18.0%(9/50)( χ2=5.420, P=0.020)for the standard dose rt-PA group and 20.0%(8/58)for the conservative treatment group( χ2=5.048, P=0.025). The incidence of intracranial hemorrhage was 8.8%(5/57)for the low-dose rt-PA group, lower than 24.0%(12/50)for the standard-dose rt-PA group( P=0.032). The incidence of extracranial complications was 15.8%(9/57)for the low-dose rt-PA group, lower than 36.0%(18/50)for the standard-dose group( P=0.017). Conclusions:For elderly patients with acute cerebral infarction on maintenance hemodialysis, intravenous thrombolytic therapy with low dose rt-PA should be considered with caution.

OBJECTIVE To investigate the effects of β-sitosterol on the function of rheumatoid arthritis （RA） fibroblastic synoviocytes MH7A cells and its mechanism. METHODS Network pharmacology was adopted to screen the targets of β-sitosterol and the targets for the treatment of RA. After the intersection of them， topological analysis was performed to find the most critical target in the treatment of RA. MH7A cells were treated with different concentrations （0， 5， 10， 20， 40 μmol/L） of β-sitosterol， and CCK-8 was used to assay cell viability for screening the optimal concentration of β-sitosterol. MH7A cells were induced by 10 ng/mL TNF-α in vitro and treated with β-sitosterol （the optimum concentration）. CCK-8 and EdU were used to detect the ability of cell proliferation. Scratch experiment and Transwell invasion assay were used to analyze cell migration and invasion. The levels of interleukin-1β （IL-1β） and IL-6 in cell supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of peroxisome proliferator-activated receptor α （PPARα） were measured by qRT-PCR and Western blot， respectively. The siRNA targeting PPARα was transfected into MH7A cells， and the effects of β-sitosterol on cell proliferation， migration， invasion， the secretion of inflammatory factors and the expression of PPARα after PPARα knockdown were detected by the above experimental methods. RESULTS PPARα was the most critical target of β-sitosterol in the treatment of RA. The optimal concentration of β-sitosterol was 20 μmol/L. Compared with model group， β-sitosterol decreased the viability of MH7A cells， and the number of proliferating cells also decreased significantly （P＜0.05）； the cell migration rate and the number of cell invasion decreased significantly （P＜0.05）. The levels of IL-1β and IL-6 were also significantly decreased （P＜0.05）， and the mRNA 15 and protein expression levels of PPARα were significantly increased （P＜0.05）. Compared with negative control small interfering RNA group， after PPARα knockdown， the cell viability increased by about 35.6% （P＜0.05）， the number of cell proliferation， the cell migration rate and the number of cell invasion increased significantly （P＜0.05）， and the levels of IL-1β and IL-6 also increased significantly （P＜0.05）. CONCLUSIONS β-sitosterol could effectively inhibit the proliferation， migration， invasion and secretion of inflammatory factors in MH7A cells， the mechanism of which may be associated with activating PPARα pathway.

The first line of clinical treatment for Guillain-Barré Syndrome (GBS) is intravenous immunoglobulin (IVIg) and plasma exchange (PE). However, the prognoses of patients vary greatly, with high disability and mortality rates. Immunotherapy has become a research hotspot in recent years. This paper reviews the research progress of GBS immunotherapy in recent years from the prospect of monoclonal antibody, immunomodulator and cytokines, in order to provide basis for treatment of GBS.

Objective:To investigate the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with maintenance hemodialysis (MHD) and acute ischemic stroke.Methods:The clinical data of 235 patients with acute ischemic stroke receiving MHD were collected in our hospital from March 2018 to October 2021. According to the treatment methods chosen by themselves, these patients were divided into control group ( n=70, only receiving standardized secondary stroke prevention), rt-PA low-dose group ( n=85, receiving rt-PA intravenous thrombolysis, 0.6 mg/kg) and rt-PA standard-dose group ( n=80, receiving rt-PA intravenous thrombolysis, 0.9 mg/kg). The effective rate 24 h after treatment, good efficacy rate 7 d after treatment, and good prognosis rate and mortality 90 d after treatment were used to evaluate the effectiveness. The incidences of intracranial hemorrhage, symptomatic intracranial hemorrhage, and severe extracranial hemorrhage 90 d after treatment were used to evaluate the safety. Results:There was no statistical difference in the good prognosis rate 90 d after treatment among the rt-PA low-dose group, the rt-PA standard-dose group and the control group (71.8%, 68.8%, and 64.3%; P>0.05), but the effective rate 24 h after treatment and good efficacy rate 7 d after treatment in the rt-PA low-dose group and rt-PA standard-dose group (44.7%, 57.7%; 46.3%, 62.5%) were both significantly higher than those in the control group (27.1%, 38.6%; P<0.05). The mortality 90 d after treatment in the rt-PA low-dose group (7.1%) was significantly lower than that in the rt-PA standard-dose group (22.5%) and control group (21.4%, P<0.05). The incidences of intracranial hemorrhage and symptomatic intracranial hemorrhage in the rt-PA low-dose group (8.2%, 3.5%) were significantly lower than those in the rt-PA standard-dose group (22.5%, 16.3%; P<0.05), and the incidences of extracranial complications and gastrointestinal bleeding (5.9%, 1.2%) were significantly lower than those in the rt-PA standard-dose group (18.8%, 10.0%; P<0.05). Conclusion:Intravenous thrombolytic therapy with 0.6 mg/kg rt-PA is recommended for acute ischemic stroke patients receiving MHD.

Objective:To investigate the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke with stress hyperglycemia under the guidance of glycosylated hemoglobin A1c (GHbA1c).Methods:The clinical data of 195 patients of acute cerebral infarction with admission blood glucose over 22.2 mmol/L and GHbA1c less than 15.59% were collected in Nankai University Affiliated Tianjin Fourth Central Hospital from January 2018 to June 2021 and analyzed retrospectively. Patients were divided into control group (60 cases), rt-PA low-dose group (0.6 mg/kg, 70 cases) and rt-PA standard-dose group (0.9 mg/kg, 65 cases) to evaluate the guiding effect of GHbA1c and the efficacy and safety of rt-PA.Results:The effective rate at 24 hours and good rate at 7 days were 61.4% (43/70) and 72.9% (51/70) in the rt-PA low-dose group, 64.6% (42/65) and 69.2% (45/65) in the rt-PA standard-dose group, respectively, both better than the control group [30.0% (18/60); χ2=18.25, P<0.001 and 46.7% (28/60); χ2=13.65, P=0.001]. The good outcome rate at 90 days was 82.8% (58/70) in the rt-PA low-dose group, which was better than 63.3% (38/60) in the control group (χ2=6.38, P=0.016), but without statistically significant difference compared with the rt-PA standard-dose group [72.3% (47/65); χ2=2.17, P=0.153]. The case fatality rate at 90 days of the rt-PA low-dose group was 7.1% (5/70), which was lower than 20.0% (13/65) in the rt-PA standard-dose group (χ2=4.82, P=0.041) and 18.3% (11/60) in the control group (χ2=5.04, P=0.030). The incidence of intracranial hemorrhage and symptomatic intracranial hemorrhage was 8.5% (6/70) and 2.9% (2/70) in the rt-PA low-dose group, lower than 20.0% (13/65; P=0.048) and 13.8% (9/65; P=0.020) in the rt-PA standard-dose group. The incidence of extracranial hemorrhage was 7.1% (5/70) in the rt-PA low-dose group, lower than 18.9% (12/65) in the rt-PA standard-dose group ( P=0.042). Conclusion:Acute cerebral infarction patients with admission blood glucose over 22.2 mmol/L can receive rt-PA treatment when GHbA1c is less than 15.59%, and 0.6 mg/kg dosage is recommended.

Objective:To investigate the safety and efficacy of intravenous thrombolysis with recombinant human tissue-type plasminogen activator (rt-PA) in acute cerebral infarction combined with hyperglycemia under the guidance of glycosylated hemoglobin A 1c (HbA1c) level in the elderly. Methods:A retrospective study was performed. Two hundred and sixty-two elderly patients with acute cerebral infarction, admitted to our hospital from January 2018 to June 2021, were chosen in this study. Patients with admission blood glucose of 2.8-22.2 mmol/L and accepted intravenous thrombolysis with standard dose of rt-PA were enrolled into control group; patients with admission blood glucose over 22.2 mmol/L and HbA1c less than 15.59% were enrolled into experimental group. The patients in the experimental group were subdivided into conservative treatment group ( n=63), rt-PA low-dose group (0.6 mg/kg, maximum dose 60 mg, n=67) and rt-PA standard dose group (0.9 mg/kg, maximum dose 90 mg, n=60) according to whether these patients received rt-PA intravenous thrombolysis or not and dosage of rt-PA. The response rate 24 h after treatment and short-term prognosis 7 d after treatment were evaluated by referring to the treatment effectiveness evaluation criteria developed by NINDS clinical trials. The long-term prognosis was evaluated by modified Rankin Scale (mRS) 90 d after treatment. The safety evaluation indexes mainly included incidences of intracranial hemorrhage and complications within 90 d of treatment. Results:(1) The response rate 24 h after treatment showed significant differences among the 4 groups ( P<0.05): that in the control group, rt-PA low-dose group, and rt-PA standard dose group was significantly higher than that in the conservative treatment group ( P<0.05); the good prognosis rate 7 d after treatment showed significant differences among the 4 groups: that in the control group, rt-PA low-dose group, and rt-PA standard dose group was significantly higher than that in the conservative treatment group ( P<0.05). (2) Ninety d after treatment, 59 patients (81.9%), 46 (73.0%), 53 (79.1%), and 46 (76.7%) in the control group, conservative treatment group, rt-PA low-dose group, and rt-PA standard dose group had good prognosis, without significant differences among each group ( P>0.05). (3) There was significant difference in the incidence of cerebral hemorrhage within 90 d of treatment among the 4 groups ( P<0.05): that in the rt-PA standard dose group and rt-PA low-dose group was significantly higher than that in the control group and conservative treatment group, and that in the rt-PA standard dose group was significantly higher than that in the rt-PA low-dose group ( P<0.05). Seven patients (9.7%), 8(12.7%), 5(7.5%), and 13(21.7%) in the control group, conservative treatment group, rt-PA low-dose group, and rt-PA standard dose group had extracranial complications: the incidence of extracranial complications in the rt-PA low-dose group was significantly lower than that in the rt-PA standard-dose group ( P<0.05). There were 7 kinds of residual neurological dysfunction in 4 groups within 90 d of treatment, among which, numbness, weakness and speech impairment were the most common. Conclusion:Elderly acute cerebral infarction patients with admission blood glucose over 22.2 mmol/L can receive rt-PA treatment when HbA1c is less than 15.59%, and 0.6 mg/kg dosage is recommended.

This paper elaborates the specific implementation process of the "research-based learning" teaching reform of genetic experiment in medical undergraduate education, including the change of teaching philosophy among teachers, the integration and expansion of experimental contents, the innovation of classroom-teaching model, the compilation of proper textbook, the update of assessment methods and the establishment of evaluation mechanism for teaching and so on. Preliminary research shows that RBL teaching reform can stimulate medical students' interest and potential in learning, and improve their practical and scientific research innovation ability.