There is no unified international guidelines or consensus on seizures and epilepsy following acute stroke reperfusion therapy so far.In this review,we briefly summarize its definitions and mechanisms.Post stroke epilepsy after reperfusion treatment is defined as patients with ischemic stroke who have received intravenous thrombolysis and/or endovascular therapy,without other definitive causes or epilepsy history before stroke,have at least two epileptic seizures occurred within 7 days of stroke onset,or at least one epileptic seizures occurred within 30 days of stroke onset.The incidence rate of epilepsy after intravenous thrombolysis is about 6.4%-20.6%,and arterial thrombectomy is about 5%.The pathophysiological mechanism of post stroke epilepsy after reperfusion treatment may be related to local hyperfusion,epileptogenic properties of tPA and hemorrhagic transformation.Higher stroke severity,cortical involvement,middle cerebral artery infarction,and early post-stroke seizures may be predictive factors for post-stroke epilepsy after reperfusion therapy.Levetiracetam and lamotrigine may be effective drugs for post-stroke epilepsy after reperfusion therapy.Sustained seizures after thrombolysis may increase the risk of death.

Objective:To discuss the effect of azathioprine(AZA)on ferroptosis in spermatocytes of the mice induced by reduced glutathione(GSH)peroxidase 4 inhibitor RSL3,and to clarify the potential mechanism.Methods:The spermatogonia GC-2 cells of the mice were randomly divided into control group(no treatment),RSL3 group(treated with 10 nmol·L-1 RSL3 for 24 h),RSL3+ferroptosis inhibitor(Ferrostatin-1,Fer-1)group(treated with 10 nmol·L-1 RSL3 for 24 h+2 μmol·L-1 Fer-1 for 12 h),RSL3+low dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+5 μmol·L-1 AZA for 12 h),RSL3+medium dose of AZA group(treated with 10 nmol·L-1 RSL3 for 24 h+10 μmol·L-1 AZA for 12 h),and RSL3+high dose of AZA group(treated with 10 nmol L-1 RSL3 for 24 h+20 μmol·L-1 AZA for 12 h).The MTT method was used to detect the activities of the GC-2 cells in various groups after treated with different concentrations of AZA and RSL3;the GSH and GSSG levels in the GC-2 cells were detected by GSH and oxidized glutathione(GSSG)detection kits;the malondialdehyde(MDA)levels in the GC-2 cells in various groups were detected by MDA detection kit;Western blotting method was used to detect the expression levels of long-chain acyl-CoA synthetase 4(ACSL4),heme oxygenase-1(HO-1),and glutathione peroxidase 4(GPX4)proteins in the cells in various groups;immunofluorescence staining was used to detect the expressions of ACSL4 protein in the cells in various groups.Results:Compared with control group,the differences in activities of the GC-2 cells in 5,10,and 20 μmol·L-1 AZA groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 30 and 40 μmol·L-1 AZA groups were significantly decreased(P＜0.01);therefore,the AZA concentration was selected to be within 20 μmol·L-1.Compared with control group,the differences of the activities of the GC-2 cells in 1,5,and 10 nmol·L-1 RSL3 groups had no significant differences(P＞0.05),while the activities of the GC-2 cells in 50,100,500,and 1 000 nmol·L-1 RSL3 groups were significantly decreased(P＜0.05 or P＜0.01);therefore,the RSL3 concentration was set to be within 10 nmol·L-1.The GSH and MDA detection kits results showed that compared with control group,the levels of GSSG and MDA in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the GSH levels were significantly decreased(P＜0.05);compared with RSL3 group,the levels of GSSG and MDA in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased(P＜0.01),while the GSH levels were significantly increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of ACSL4 and HO-1 proteins in the GC-2 cells in RSL3 group were significantly increased(P＜0.05),while the expression level of GPX4 protein was significantly decreased(P＜0.01);compared with RSL3 group,the expression levels of GPX4 protein in the GC-2 cells in RSL3+Fer-1 group and RSL3+AZA group were significantly increased(P＜0.05),while the expression levels of ACSL4 and HO-1 proteins were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the expression amount of ACSL4 protein in the GC-2 cells in RSL3 group was significantly increased,and compared with RSL3 group,the expression amounts of ACSL4 protein in the cells in RSL3+Fer-1 group and RSL3+AZA group were significantly decreased.Conclusion:AZA can alleviate the ferroptosis-induced by RSL3 in spermatocytes of the mice.

Objective To explore the histomorphology and related indicators in a rat model of skeletal muscle injury in an artificial experimental chamber as special environment in Northwest China to stimulate a hot and dry desert environment in order to screen the evaluation indicators of skeletal muscle injury in a hot and dry environment.Methods Eighteen male SD rats (8 weeks old)were randomly divided into blank control group (room temperature,free movement),room temperature exercise group,and hot and dry exercise group,with 6 rats in each group.After the rats were subjected to adaptation training for 3 d (a 3-D exercise treadmill,speed:16 m/min,slope:-16°,time:5～10 min),the rats in the 2 exercise groups were subjected to a treadmill once per day at a speed of 19.3 m/min and a slope of-16°till the end of exhaustion,and those in the hot and dry exercise group were housed in an artificial experimental chamber at a temperature of (40±1 )℃,a humidity of (10±2)％.After 6 d of continuous exercise,the rat soleus muscle tissue was taken to observe the pathological changes,and the serum samples were detected for skeletal muscle injury markers,inflammatory factors,oxidative stress related factors,hormones and other related indicators. Results When compared with the blank control group and the room temperature exercise group,the hot and dry exercise group had significantly higher concentrations of creatine kinase (CK),creatine kinase isoenzyme (CK-MB)and muscle-specific creatine kinase (CK-MM)(P<0.05 ),elevated contents of TNF-α,IL-1βand IL-6 (P<0.05),raised malondialdehyde (MDA)content and lower superoxide dismutase (SOD)activity (P<0.05 ),lower testosterone (T)but higher corticosterone (Cort)levels and thus lower testosterone/corticosterone (T/Cort)ratio (P<0.05 ).The markers of skeletal muscle injury,CK,CK-MB and CK-MM were positively correlated with the pro-inflammatory cytokines,TNF-α,IL-1βand IL-6 (P<0.05),positively with the antioxidant indicator MDA but negatively with SOD (P<0.05 ),and positively correlated with Cort level and negatively with T level and T/Cort ratio (P<0.05).Conclusion A stable rat model of skeletal muscle injury in a hot and dry desert environment is successfully constructed.The severity of skeletal muscle injury is greater in rats in a hot and dry desert environment than those in a normal temperature environment. TNF-α and IL-1β are found to be indirect indicators to evaluate skeletal muscle injury in the environment.

Objective:To explore the effect of hip arthroscopy on improving the cross-sectional kinematics of the lower limbs in patients with femoral acetabular impingement (FAI).Methods:Eight FAI patients who underwent hip arthroscopy in the Department of Sports Medicine of Peking University Third Hospital from October 2021 to February 2022 were prospectively included, including 3 males and 5 females, with an age of 35.3±13.0 years (range 17-53 years), height of 168.0±12.8 cm (range 154-192 cm), weight of 61.1±8.5 kg (range 52-74 kg) and body mass index of 21.7±2.6 kg/m 2 (range 17.6-24.5 kg/m 2). There were 3 left hips and 5 right hips. FADIR (flexion, adduction and internal rotation test) was positive in all patients and FABER (flexion, abduction and external rotation test) was positive in 4 patients. Modified Harris hip score (mHHS) and visual analogue scale (VAS) of the affected hip joint were compared before the surgery and at the follow-up of 10 months. By using a markerless motion capture system, foot progression angles during normal gait, double-leg squat, forward lunge, single-leg standing and stepping in place were measured and compared before the surgery and at the follow-up of 10 months postoperative results. Results:All the 8 patients underwent the surgery successfully and were followed up for 11.0±1.2 months. The mHHS scores before the surgery and at the follow-up of 10 months were 60.9±20.5 vs. 82.9±7.3 with significant difference ( t=-3.07, P=0.018). The iHOT-12 scores before the surgery and at the follow-up of 10 months for the affected hips were 51.4±23.7 vs. 79.2±14.6 with significant difference ( t=-3.76, P=0.007). The VAS scores before the surgery and at the follow-up of 10 months were 4.6±2.3 vs. 1.5±0.9 with significant difference ( t=3.16, P=0.016). There was no significant difference in foot progression angle between the healthy side and the affected side for all movement trials before the surgery and at the follow-up of 10 months ( P>0.05). During normal gait, the postoperative and preoperative foot progression angles for the healthy side and the affected side were 26.52°±5.97 vs. 34.4°±7.20° and 24.41°±3.70° vs. 30.80°±6.43°with significant reduction ( t=2.83, P=0.013; t=3.05, P=0.041). While there was no significant difference in foot progression angles for double-leg squat, forward lunge, single-leg standing and stepping in place before the surgery and at the follow-up of 10 months ( P>0.05). Conclusion:Hip arthroscopy can change the cross-sectional kinematic characteristics of the lower limbs, potentially improving the progression angle in FAI patients.

Objective: To study the mechanism of Pirfenidone (PFD) inhibiting the invasion of biliary tract tumors through cancer associated fibroblasts ( CAF) ． Methods: Primary CAF were extracted from the tumor tissues of patients with biliary tract tumor，and the marker proteins of CAF，including vimentin (VIM) ，α-smooth muscle actin ( α-SMA) and fibroblast activating protein ( FAP) were detected by Western blot．Phalloidin experiment showed the function of fibroblast cytoskeleton．ELISA and Western blot were used to verify the difference of TGF-β expression between normal fibroblasts ( NF) and CAF．The functional change of CAF was observed by adding PFD to CAF．The expression of TGF-β in CAF was verified by ELISA，quantitative real-time PCR (qRT-PCR) and Western blot．The change of TGF-β in serum was verified by subcutaneous tumor mouse model．The change of collagen contractile function in CAF was observed by collagen contractile test．The changes of MMP2 and MMP9 in CAF medium were observed by gelatin enzyme assay．The changes of SMAD signaling pathway protein in CAF were detected by Western blot. Results : The related marker proteins VIM，α-SMA and FAP of CAF were highly expressed， and the filamentous actin (F-actin) of CAF was abundant．ELISA showed that the expression of TGF-β in CAF was enhanced．Western blot experiment confirmed that CAF had stronger collagen function．Western blot，PCR and related phenomenon experiments showed that PFD could inhibit collagen production and TGF-β expression in CAF. SMAD signaling pathway-related protein experiments demonstrated that PFD could affect tumor invasion by inhibiting TGF-β/ SMAD signaling pathway． Conclusion The function of CAF extracted from cancer patients is dominated by collagen production，while PFD inhibits the collagen production and collagen remodeling related processes of CAF through TGF-β/ SMAD signaling pathway to inhibit tumor invasion.

Objective : To study the mechanism of Pirfenidone (PFD) inhibiting the invasion of biliary tract tumors through cancer associated fibroblasts ( CAF) ． Methods : Primary CAF were extracted from the tumor tissues of patients with biliary tract tumor，and the marker proteins of CAF，including vimentin (VIM) ，α-smooth muscle actin ( α-SMA) and fibroblast activating protein ( FAP) were detected by Western blot．Phalloidin experiment showed the function of fibroblast cytoskeleton．ELISA and Western blot were used to verify the difference of TGF-β expression between normal fibroblasts ( NF) and CAF．The functional change of CAF was observed by adding PFD to CAF．The expression of TGF-β in CAF was verified by ELISA，quantitative realtime PCR (qRT-PCR) and West- ern blot．The change of TGF-β in serum was verified by subcutaneous tumor mouse model．The change of collagen contractile function in CAF was observed by collagen contractile test．The changes of MMP2 and MMP9 in CAF me- dium were observed by gelatin enzyme assay．The changes of SMAD signaling pathway protein in CAF were detec- ted by Western blot. Results : The related marker proteins VIM，α-SMA and FAP of CAF were highly expressed， and the filamentous actin (F-actin) of CAF was abundant．ELISA showed that the expression of TGF-β in CAF was enhanced．Western blot experiment confirmed that CAF had stronger collagen function．Western blot，PCR and related phenomenon experiments showed that PFD could inhibit collagen production and TGF-β expression in CAF. SMAD signaling pathway-related protein experiments demonstrated that PFD could affect tumor invasion by inhibi- ting TGF-β/ SMAD signaling pathway Conclusion The function of CAF extracted from cancer patients is dominated by collagen production，while PFD inhibits the collagen production and collagen remodeling related processes of CAF through TGF-β/ SMAD signaling pathway to inhibit tumor invasion.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective To investigate the effect of breast conserving surgery on neurotensin (NTS) and its receptor 1(NTR1) in patients with breast cancer.Methods From May 2012 to May 2015,200 patients with breast cancer,aged 44.7 years(range,32-56 years),were treated at Tiantan Hospital,Capital Medical University.All patients were divided into control group (n =100) and observation group (n =100).The patients in the control group were treated with radical operation and the patients in the observation group were treated with breastconserving surgery.The positive rate of NTS and NTR1 before and 1 week after operation,WHOQOL-100 (It includes four aspects:physiological state,psychological state,environmental condition and social function) 1 d before surgery,3 months and 6 months after surgery,and the incidence of postoperative complications 1 week after surgery were compared between the two groups.Measurement data with normal distribution were described as mean± standard deviation (Mean ± SD) and analyzed by the t test.Count data were analyzed by chi-square test.Results The positive rate of NTS (17.00％) in the observation group was significantly lower than that in the control group (36.00％) (t =9.267,P =0.002),The positive rate of NTR1 (19.00％) was significantly lower than that in the control group (33.00％) (t =5.094,P =0.024).The physiological status,psychological state,environmental condition and social function of 3 months after surgery of the observation group were (62.57 ± 5.73),(63.48 ±5.91),(68.73 ±6.32),(64.06 ±5.94) scores,respectively,and the control group were (53.47 ±5.38),(55.62 ±5.54),(60.38 ±6.14),(55.86 ±5.66) scores,respectively,showing statistically significant differences between the two groups (P ＜ 0.05).The physiological status,psychological state,environmental condition and social function of 6 months after surgery were (73.74 ±t 6.19),(76.27 ± 6.32),(78.85 ±6.77),(73.53 ±6.58) scores in the observation group,and (64.18 ±5.67),(67.38 ±6.02),(69.64 ± 6.43),(63.28 ± 6.17) scores in the control group,showing statistically significant differences between the two groups (P ＜ 0.05).The incidence of postoperative complications in the observation group (6.00％) was significantly lower than that in the control group (18.00％) (P ＜ 0.05).Conclusion Breast conserving surgery can reduce the expression level of NTS and NTR1 in breast cancer patients,It is related to reducing the incidence of postoperative complications and improving the quality of life of patients.

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