Gap junction proteins have a significant impact on the propagation of neuroinflammation after cerebral ischemia.Connexin 43(Cx43),the principal connexin in the central nervous system,typically assembles hexameric hemichannels in an oligomeric state that dock with hemichannels on adjacent cells to form gap junction channels.Ordinarily,the likelihood of cell surface hemichannels opening is minimal.However,during cerebral ischemia,the excessive activation of Cx43 hemichannels leads to the liberation of a substantial quantity of ions(Na+,Cl-,Ca2+,and K+),glutamate,aspartate,and adenosine triphosphate(ATP),thereby resulting in impairment of adjacent cells and aggravation of neuronal injury.Furthermore,the activation of Cx43 hemichannels triggers the release of inflammatory factors,which exhibits a strong association with the activation of NLRP3 inflammasome after cerebral ischemia.Hence,the modulation of Cx43 hemichannels presents a potential avenue for mitigating neuroinflammation and subsequently diminishing cerebral ischemic injury.This article focuses on the relationship between Cx43 hemichannels and NLRP3 inflammasome activation,as well as its role in cerebral ischemia,all of which provide novel insights and therapeutic approaches for managing cerebral ischemia.

Objective To explore the effects of M1 polarization of microglia on secondary damage in the thalamus after cerebral cortical infarction.Methods A focal cortical infarct model of adult male SD rats was pre-pared using eletrocoagulation and randomized into Sham and model groups at different time points 1～4 weeks after surgery.Based on the assessment of neurofunctional changes in each group of rats,immunohistochemistry was used to observe the number and morphology of NeuN,GFAP and Iba-1 positive cells in(Ventral posterior nucleus of thalamus,VPN)of the ipsilateral thalamus after distal middle cerebral artery occlusion(dMCAO).Immunofures-cence was used to detect the number and morphology of M1 microglia marker(Iba-1+/CD68+cells)and M2 microg-lia marker(Iba-1+/CD206+cells)in VPN of the ipsilateral thalamus after dMCAO.Western blot was used to detect the expression levels of IL-1β,TNF-α,IL-10 and Arg-1 in VPN of the ipsilateral thalamus after dMCAO.Results The results of immunohistochemistry showed a significant decrease in NeuN positive cells and an increase in the density of GFAP and Iba-1 in the ipsilateral VPN of rats after dMCAO when compared with Sham group(P<0.001).Compared with sham group,the protein levels of TNF α and IL-1β were elevated in the ipsilateral VPN elevated(P<0.05).In addition,the model group rats exhibited higher Bederson scores,beam-walking test and adhesive removal test scores after dMCAO compared with Sham group(P<0.05).The numbers of M1 microglia marker(Iba-1+/CD68+cells)were significantly increased when compared with M2 microglia marker(Iba-1+/CD206+cells)in ipsilateral VPN of rats after dMCAO.Conclusion M1 polarization of microglia may play an essential role in secondary damage of thalamus after cerebral cortical infarction.

A 72-year-old male patient with right lung squamous cell carcinoma treated with 1 cycle of pembrolizumab combination chemotherapy and pembrolizumab 200 mg monotherapy.After 20 days of treatment,a small amount of erythema appeared around the mouth,head,neck,chest and back,accompanied by itching.Then the lesions aggravated progressively,spreading to the head,limbs,buttocks and perianal area,with blisters and epidermal detachment and necrosis,and the lesions involved＞70％of the body surface area,and the pain was obvious.After multidisciplinary consultation,toxic epidermal necrolysis(TEN)was considered.The patient's lesions gradually improved and regressed after treatment with hormones,adjunctive therapy with intravenous immunoglobulin,wound care,infection prevention and nutritional support.TEN adverse reactions were highly likely to be associated with pembrolizumab.This paper reviewed the literature on the cases of TEN induced by pembrolizumab.It analyzed the clinical characteristics and drug treatment strategies of TEN induced by pembrolizumab,to improve clinical staff's ability to recognize and manage immunosuppressant-related skin toxicity and improve the prognosis of tumor patients.

As the main water channel expressed in the brain,aquaporin 4(AQP4)has been implicated in the pathological process of ischemic stroke.After ischemic stroke,the expression,phosphorylation and polarity distribution of AQP4 are affected by the process of transcription and post-translational modification.The paper summarized the basic structure,physiological function,dynamic expression changes and mechanisms of AQP4 in this review,specifically discussing the role of AQP4 in cerebral edema,blood-brain barrier permeability and neuroinflammation after ischemic stroke,offering an up-to-date perspective on further effective therapeutic strategies for ischemic stroke.

The disorder of autophagy lysosomal pathway (ALP) is an important pathogenesis of neuronal damage after cerebral ischemia, and the restoration of ALP may alleviate neuronal damage after cerebral ischemia. As the main transcription factor regulating ALP, transcription factor EB (TFEB) can directly regulate autophagosome generation, autophagosome-lysosome fusion, and autophagic flux by regulating the expression of autophagic genes and lysosomal genes. Therefore, regulating TFEB can alleviate ALP dysfunction and thereby reduce cerebral ischemic damage. This article reviews the structure, biological function of TFEB and its role in regulating ALP to alleviate neuronal damage after cerebral ischemia.

Objective:To prepare the resiquimod-loaded lipid microbubbles R848-MBs, evaluate their enhanced ultrasound imaging and high intensity focused ultrasound (HIFU) ablation effects, and explore their ability to improve tumor immune microenvironment synergize with HIFU.Methods:R848-MBs were prepared by the thin film hydration-mechanical shock method; The basic characteristics and safety of R848-MBs were detected, the HIFU controlled-release characteristics were verified in vitro and the drug metabolism and biological distribution were investigated in vivo. The ability of enhancing ultrasound imaging was observed in vitro and in vivo. To investigate the enhanced HIFU ablation effect of R848-MBs, six EMT6 tumor-bearing mice were randomly divided into HIFU group and R848-MBs+ HIFU group, three mice in each group, the changes in contrast average sound intensity before and after ablation in mouse tumor areas and the change of ultrasound image gray value in tumor area were evaluated, the tumor were resected to observe the coagulative necresis by TTC staining and HE staining. Forty-five tumor-bearing mice were randomly divided into control group, Free R848 group, HIFU group, Blank-MBs+ HIFU group and R848-MBs+ HIFU group, nine mice in each group. On the third day after treatment, 3 mice in each group were randomly selected and killed, to evaluate the ability of R848-MBs to improve tumor immune microenvironment synergize with HIFU. The expression level of CRT on the surface of tumor cells were detected by immunofluorescence staining, the proportion of mature DC in lymph nodes, spleen, and CD8 + T cells in spleen were detected by flow cytometry. The treatment effectiveness of each group( n=6) were evaluated by measuring tumor volume, observing and drawing survival curves. Results:The R848-MBs lipid microbubbles with good safety were successfully prepared, with a concentration of 2.58×10 9/ml, as spherical bubbles under optical microscope and laser confocal microscopy, in a particle size of (1.72±0.11)μm, at a surface potential of (-10.16±0.73)mV. The cumulative drug release was up to 83.44% after HIFU (90 W, 3 s) in vitro. The concentration of R848 in plasma decreased rapidly, and the drug concentration in tumor tissue of the R848-MBs+ HIFU group was higher than that of the R848 group 24 hours after treatment ( P<0.01). The ultrasound imaging of R848-MBs was significantly enhanced in contrast mode in vitro and in vivo; R848-MBs can significantly enhance the HIFU ablation effect, the contrast average sound intensity change in the tumor area before and after ablation in the R848MBs+ HIFU group was greater than that in the R848 group ( P<0.05), and the immediate ultrasound grayscale value change in the HIFU+ R848-MBs group was 46.34±3.21, which was significantly greater than that in the HIFU group (10.67±1.53), with statistical significance ( P<0.000 1). Coagulation necrosis was observed in tumor HE staining and TTC staining. The results of treatment efficacy in vivo showed that R848-MBs+ HIFU group had the strongest therapeutic effect, and R848-MBs combined with HIFU treatment could significantly prolong the survival period of mice compared with intravenous injection of free R848 ( P<0.01). Immunofluorescence staining and flow cytometry results showed an increase in the expression level of CRT on the surface of tumor tissue in the R848-MBs combined with HIFU group, and the percentage of mature DC in tumor draining lymph nodes (58.53±1.04)% were significantly higher than those in the HIFU group (37.56±2.13)% ( P<0.001), and the percentage of mature DC in the spleen (70.65±1.91)% were significantly higher than those in the HIFU group (36.46±3.89)% ( P<0.001), the percentage of CD8 + T cells in the spleen (27.46±3.04)% was significantly higher than that in the HIFU group (18.69±0.29)% ( P<0.01). Conclusions:The HIFU controlled-release lipid microbubbles R848-MBs can not only enhance the efficiency of HIFU ablation, but also improve the tumor immune microenvironment.

CCAAT/enhancer binding protein β (C/EBPβ), a transcriptional factor of the basic-leucine zipper family, can regulate the transcription activity of downstream target genes. After acute cerebral ischemia, the activity of C/EBPβ changes, and participates in the process of cerebral ischemia injury by regulating neuronal apoptosis and inflammation. This article reviews the molecular biological characteristics of C/EBPβ and its expression changes and role in acute cerebral ischemia, providing a basis for developing new neuroprotective drugs for acute cerebral ischemia using C/EBPβ as therapeutic target.

p75 neurotrophin receptor (p75 NTR) is a member of the tumor necrosis factor receptor superfamily, which interacts with tropomyosin receptor kinase (Trk) receptor or binds neurotrophic factors. It mediates a variety of complex signal transduction pathways, induces synaptic growth and affects cell survival. After acute cerebral ischemia, p75 NTR binds effector factors such as pro-nerve growth factor (proNGF) and sortilin, activating downstream apoptotic signal molecules and leading to neuronal death. Therefore, elucidating the pathways and molecular mechanisms of p75 NTR that mediate neuronal apoptosis in acute cerebral ischemia is of great significance for the development of new therapeutic drugs for acute cerebral ischemia.

Objective:To analyze the application value of the mechanical thrombectomy system in the treatment of acute limb ischemia.Methods:The clinical data of 50 patients with lower limb ischemia who were treated with the Rotarex mechanical thrombectomy system from Jun 2017 to Sep 2019 were retrospectively analyzed.Results:In 4 cases of popliteal artery rupture occurred during the operation. The success rate of the operation was 92%. Catheter-directed thrombolysis was used in 7 cases, percutaneous transluminal angioplasty was used in 4 cases and percutaneous transluminal angioplasty combined with stent implantation was used in 39 cases. The ankle-brachial index of these 50 patients before and after operation was 0.18±0.24 and 0.64±0.28 respectively ( t=12.87, P<0.001). Treatment was successful in 43 cases. Follow-up ranged from 1 to 24 months, 5 cases were amputated, 2 cases had no improvement of toe ulcer gangrene, 9 cases had thrombus recurrence, and no complications such as bleeding were observed. The primary patency rates at 3, 6 and 12 months were 92%, 84% and 74%, respectively. Conclusion:The mechanical thrombectomy system is safe and effective in the treatment of acute lower limb ischemia with ideal short-term patency.

Objective To investigate the safety and short-term outcomes of laparoscopic abdominoperineal resection with pelvic peritoneum closure (LARP-PPC) for low rectal cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 132 patients with low rectal cancer who were admitted to Ruijin Hospital of Shanghai JiaoTong University School of Medicine from January 2014 to December 2017 were collected.There were 81 males and 51 females,aged from 45 to 83 years,with an average age of 62 years.Among the 132 patients,60 undergoing LARP-PPC were allocated into LARP-PPC group,and 72 patients undergoing conventional LARP were allocated into LARP group.All the patients received standardized preoperative and postoperative treatments.Observation indicators:(1) surgical and postoperative conditions;(2) postoperative pathological examination;(3) postoperative complications.The measurement data with normal distribution were expressed as Mean±SD,and the t test was used for comparison between groups.The measurement data with skewed distribution were expressed as M (range),and the Mann-Whitney U test was used for comparison between groups.The count data were expressed as absolute numbers,and the chi-square test or the Fisher exact probability was used for comparison between groups.Mann-Whitney U test was used for comparison of ordinal data between groups.Results (1) Surgery and postoperative conditions:all the patients in the two groups underwent successful surgery without conversion to open surgery.The operation time,volume of intraoperative blood loss,time to first flatus,and time to first liquid intake of the LARP-PPC group were (163±45) minutes,168 mL(range,85-280 mL),2 days(range,1-5 days),3 days(range,2-6 days),versus (155±39) minutes,160 mL(range,100-305 mL),3 days(range,1-7 days),4 days(range,2-7 days) of the LARP group;there was no differencebetween the two group (t =1.113,Z =-1.623,-1.468,-0.321,P＞0.05).The duration of postoperative hospital stay in the LARP-PPC group and the LARP group were 16 days (range,11-21 days) and 19 days (14-24 days),respectively,with a significant difference between the two groups (Z =-5.888,P＜0.05)].In the LARP-PPC group,time of PPC was (13± 3) minutes.(2) Postoperative pathological examination:the length of specimen,the number of lymph node dissection,tumor diameter,cases with high-,middle-,and low-differentiated tumor in the LARP-PPC group was (18±4)cm,16±t5,(3.7±1.4)cm,10,34,16 in the LARP-PPC group,and (18±4)cm,16±5,(3.9±1.5) cm,13,41,18 in the LARP group,showing no significant difference between the two groups (t =0.779,0.390,0.703,Z=-0.267,P＞0.05).(3) Postoperative complications:cases with perineal wound infection,delayed perineal wound healing,intestinal obstruction,and perineal hernia were 2,1,1,0 in the LARP-PPC group,and 12,10,8,6 in the LARP group,showing significant differences between the two groups (x2 =6.137,6.400,P＜0.05).There were 2 and 4 patients with urinary tract infection in the LARP-PPC group and the LARP group,respectively,showing no significant difference between the two groups (P ＞ 0.05).Conclusion LARP-PPC is safe and feasible for the treatment of low rectal cancer,which can significantly reduce postoperative perineal-related complications and consequently shorten postoperative hospital stay.