BACKGROUND:Troxerutin has been found to have a significant ameliorative effect on brain disorders,but there are fewer studies on the effects of troxerutin on the treatment of cerebral infarction and on neuronal cells. OBJECTIVE:To investigate the mechanism by which troxerutin regulates nuclear factor-κB signaling pathway to reduce brain injury and neuronal apoptosis in cerebral infarction rats. METHODS:Fifty clean grade rats were randomized into healthy group,model group,and troxerutin+nuclear factor-κB agonist group,troxerutin group,and nuclear factor-κB inhibitor group.Except for the healthy group,all other groups were used to establish a rat model of cerebral infarction by arterial ligation.The healthy and model groups were treated once a day with an equal amount of physiological saline by gavage.The troxerutin+nuclear factor-κB agonist group was intervened with 72 mg/kg troxerutin by gavage+20 mg/kg RANK intraperitoneally.The troxerutin group was treated with 72 mg/kg troxerutin by gavage.The nuclear factor κB inhibitor group was intervened intraperitoneally with 120 mg/kg nuclear factor κB inhibitor pyrrolidine disulfiram.Administration in each group was given once a day for 30 continuous days.Zea-longa was used to detect neurological damage in rats,hematoxylin-eosin staining was used to observe pathological changes,TUNEL was used to detect neuronal apoptosis,and immunoblotting and PCR were used to detect the expression of nuclear factor-κB p65 and nuclear factor-κB p50 at protein and mRNA levels,respectively. RESULTS AND CONCLUSION:Compared with the healthy group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65,nuclear factor-κB p50 mRNA and protein expression levels were elevated in the model group(P＜0.05).Compared with the model group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were decreased in the troxerutin+nuclear factor-κB agonist group(P＜0.05).Compared with the troxerutin+nuclear factor-κB agonist group,the neurological function score,neuronal apoptosis rate,nuclear factor-κB p65 and nuclear factor-κB p50 mRNA and protein expression levels were reduced in the troxerutin group and nuclear factor-κB inhibitor group(P＜0.05).In addition,there was no difference between the troxerutin group and the nuclear factor-κB inhibitor group(P＞0.05).In the model group,there was a large number of cytoplasmic vacuolation,obvious edema and necrosis,and a large number of inflammatory cell infiltrations.In the troxerutin+nuclear factor-κB agonist,the swelling of brain tissue was reduced,and reticulate structures and condensed cells were reduced,still with some edema.In the troxerutin group and nuclear factor-κB inhibitor group,brain tissue swelling,neuronal edema degeneration,cytoplasmic vacuolation and neuronal nucleus consolidation were reduced,and the inflammatory cell infiltration was significantly decreased.To conclude,troxrutin can reduce the expression of neurological impairment,inhibit neuronal apoptosis and improve the pathological injury of brain tissue in rats with cerebral infarction,and its mechanism of action may be related to the modulation of nuclear factor-κB expression and related signaling pathways.

Objective To explore the effects of Buyang Huanwu Decoction on neuronal cell apoptosis after cerebral ischemia based on mediating Cav1 in regulating Wnt pathway.Methods Male wild-type(WT)and Cav1-/-(KO)C57BL/6 mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group(18.5 g/kg).Cerebral ischemia model was prepared using middle cerebral artery occlusion method,and drug intervention was given for 14 days.Neurobehavioral score was performed,HE staining was used to observe the morphology of ischemic cortical area of brain tissue,TUNEL staining was used to detect neuronal apoptosis in ischemic cortical area,immunohistochemistry was used to detect the expressions of apoptosis related proteins and Wnt1,glycogen synthase kinase 3β(GSK3β)and β-catenin protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurobehavioral score of the model group mice significantly increased,neuronal cells in the ischemic cortical area showed vacuolar changes,with nuclear condensation and widened intercellular spaces,the apoptosis rate of nerve cells significantly increased,with increased expressions of Bax,GSK3β and decreased expressions of Bcl-2,Wnt1 and β-catenin(P<0.01).Compared with the same genotype model group,the neurobehavioral score of mice in Buyang Huanwu Decoction group were significantly decreased,the pathological damage of the ischemic cortical area improved,the apoptosis rate of nerve cells decreased,the expressions of Bax and GSK3β decreased,and the expressions of Bcl-2,Wnt1 and β-catenin increased(P<0.01).Compared with the WT model group,the KO model group showed an increase in neurobehavioral score,aggravated damage in ischemic cortical area,significantly increased neuronal apoptosis rate,and increased expression of GSK3β(P<0.05).Compared with the WT Buyang Huanwu Decoction group,the KO Buyang Huanwu Decoction group showed an increase in neurobehavioral score,aggravated damage in ischemic cortical area,significantly increased neuronal apoptosis rate,increased expressions of Bax and GSK3β,and decreased expressions of Bcl-2,Wnt1 and β-catenin(P<0.01).Conclusion Buyang Huanwu Decoction can inhibit neuronal cell apoptosis after cerebral ischemia,and its mechanism may be related to regulating the expressions of apoptosis-related proteins by mediating Cav1 to regulate the Wnt signaling pathway.

Objective To explore the mechanism of Buyang Huanwu Decoction against cerebral ischemia-reperfusion injury in rats by regulating lipid metabolism through the cAMP/PKA/PPARγ pathway.Methods 60 rats were randomly divided into sham operation group(Sham),model group(Model),Buyang Huanwu Decoction low-dose group(BHD-L),Buyang Huanwu Decoction medium-dose group(BHD-M),Buyang Huanwu Decoction high-dose group(BHD-H)and Butylphthalide group(NBP).The cerebral ischemia-reperfusion model was prepared by transient middle cerebral artery embolization.The BHD low-,medium-and high-groups were given different doses of Buyang Huanwu Decoction(6.413,12.825,25.65 g·kg-1)by intragastric administration.The NBP group was administered with Butylphthalide(54 mg·kg-1).The sham operation group and the model group were administered with an equal volume of distilled water,all given for 14 days.The rats were subjected to neurobehavioral scoring.HE staining was used to observe brain pathological changes,and the kit was used to detect the levels of phosphocholine(PC),phosphatidylethanolamine(PE),diacylglycerol(DAG),and free fatty acid(FFA)on the ischemic side.RT-qPCR and Western Blot were applied to detect the mRNA and protein expressions of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and peroxisome proliferator-activated receptor γ(PPARγ).Results Compared with the sham group,the neurological deficit score was significantly increased(P＜0.01),pathomorphological damage in ischemic cortex was found,the contents of PC and PE were reduced,the contents of DAG and FFA were increased(P＜0.01),and cAMP mRNA expression increased(P＜0.05)in the model group.Compared with the model group,the neurological deficit score of the BHD-L group was decreased(P＜0.05),and the neurological deficit score of the BHD-M,BHD-H and NBP groups was significantly decreased(P＜0.01),the cells in each treatment group were regularly arranged,the intercellular spaces were reduced,and the normal cells were increased.PC and PE were significantly increased,DAG and FFA were significantly decreased(P＜0.01)in the BHD-M,BHD-H and NBP groups.PC was increased,FFA and DAG were decreased in the BHD-L group(P＜0.05,P＜0.01).The mRNA level of PPARγ was increased in the BHD-L group(P＜0.05),and the mRNA and protein levels of cAMP,PKA,and PPARγ were increased in the other treatment groups(P＜0.05,P＜0.01).Conclusion Buyang Huanwu Decoction has a neuroprotective effect on cerebral ischemia-reperfusion injury rats,and its mechanism may be related to regulating the expression of key factors in the cAMP/PKA/PPARγ signaling pathway and lipid metabolism.

Objective:To analyze the application and regularity of acupoint selection of Sanyinjiao (SP 6) based on data mining.Methods:Search for literatures in CNKI, Wanfang, VIP, and Pubmed, the clinical researches of acupuncture on Sanyinjiao (SP 6) point were selected, according to the inclusion and exclusion criteria, and the retrieval period was from database construction to September 30th, 2021. Excel 2016, SPSS Statistics 25.0, SPSS Modeler 18.0 were used to perform descriptive analysis, association analysis and cluster analysis.Results:After literature screening, a total of 261 literatures were included, involving 73 kinds of diseases, mainly including mental and behavioral disorders, genitourinary diseases, endocrine and nutritional metabolism diseases and nervous system diseases. The most frequently used acupoints in Sanyinjiao (SP 6) compatibility are Zusanli (ST 36), Baihui (GV 20), Guanyuan (CV 4) and Taichong (LR 3), most of which focus on stomach meridian, conception channel, governor channel and bladder meridian. Seven categories were extracted among high-frequency acupoints by cluster analysis. The association rule analysis showed that the commonly used combination of Sanyinjiao (SP 6) were Zusanli (ST 36)-Sanyinjiao (SP 6), Baihui (GV 20)-Sanyinjiao (SP 6), and Guanyuan (CV 4)-Sanyinjiao (SP 6).Conclusions:Sanyinjiao (SP 6) is widely used in clinical application, and it is always compatible with stomach meridian, conception vessel, governor channel acupoints, especially those acupoints on the outer and inner meridians and the upper and lower parts. Sanyinjiao (SP 6) combined with other acupoints can treat diseases of multiple systems, such as insomnia, stroke, anxiety and depression, dysmenorrhea, infertility, etc. Clustering and association analysis found the core compatibility law of Sanyinjiao (SP 6), which can be used as a reference for clinical acupoint selection.

Objective:To investigate the value of combined detection of neutrophil gelatinase-associated lipocalin(NGAL), cystatin C(CysC)and heme oxygenase-1(HO-1)in the early diagnostic of acute kidney injury(AKI)caused by acute paraquat poisoning(APP)in elderly patients.Methods:One hundred and two elderly APP patients admitted to the emergency department of our hospital from May 2015 to June 2019 were assigned to the observation group, and 50 patients who took physical examinations served as the control group.The observation group was divided into the AKI sub-group(n=59)and the non-AKI sub-group(n=43)based on whether AKI occurred within 72 h of admission.Serum levels of NGAL, CysC, HO-1 and creatinine(Scr)were detected in all APP patients at 0 h(admission), 12 h, 24 h, 48 h and 72 h. Measurements of the same parameters were made on the day of physical examination for the control group.The correlations of serum levels of NGAL, CysC and HO-1 with the occurrence of AKI were analyzed.Relative operating characteristic curve(ROC)was drawn to analyze the diagnostic value of NGAL, CysC, HO-1 and the combination of the three for the early diagnosis of renal injury in APP patients.Results:Serum levels of NGAL, CysC, HO-1 and Scr at admission showed no significant difference between the AKI sub-group, non-AKI sub-group and control group( P>0.05). After admission, all the parameters showed an upward trend in the observation group.Serum levels of NGAL, CysC and HO-1 at 12 h after admission( P<0.05)and Scr levels at 72 h after admission( P<0.05)were significantly different between the AKI sub-group and the non-AKI sub-group.Correlation analysis showed that serum NGAL, CysC and HO-1 levels were positively correlated with the occurrence of AKI in APP patients at 12 h, 24 h, 48 h and 72 h after admission, with the best correlation at 48 h after admission(NGAL: r=0.203, 0.545, 0.707 and 0.560, P<0.05; CysC: r=0.242, 0.340, 0.754 and 0.467, P<0.05; HO-1: r=0.249, 0.536, 0.677 and 0.509, P<0.05). The area under ROC curve predicted by NGAL, CysC, HO-1, Scr and NGAL+ CysC+ HO-1 for AKI at 48 h after admission was 0.777, 0.718, 0.888, 0.602 and 0.969, respectively. Conclusions:Serum levels of NGAL, CysC and HO-1 are significantly elevated at 12 h after admission in elderly APP patients, and reach the peak at 48 h after admission.Each of them can give an earlier diagnosis for AKI than Scr, and the combination of the three provides a higher diagnostic accuracy for AKI.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

To explore the effect of Naoshuming decoction on cerebral ischemic rats.
 Methods: The model of cerebral ischemia in rats was established via middle cerebral artery occlusion (MCAO). The MCAO model rats were randomly divided into a model group (n=36), a Naoshuming decoction at high dose group (n=36), a Naoshuming decoction at middle dose group (n=36) and a Naoshuming decoction at low dose group (n=36). In addition, a normal group (n=12) and a sham operation group (n=12) were included. Rats in each group were killed on the 3rd, 7th, and 14th day to detect relevant indicators. The Ayelet Levy 14 method was used to score the neurological function. Immunohistochemical method was used to detect the protein expression of nuclear factor kappa-B (NF-κB)/p50, NF-κB/p65, tumor necrosis factor-α (TNF-α), and IL-1β. The quantitative real-time PCR were used to detect the mRNA expression of NF-κB, TNF-α and IL-1β. 
 Results: Compared with the sham group, at each time point, the inflammation indexes in the model group and different dose of Naoshuming decoction groups were significantly enhanced, and all of them showed neurological dysfunction. But the inflammatory indexes and neurological function scores would were gradually improved with the pass of time. Compared with the model group, the neurological dysfunction, the protein levels of NF-κB/p50, NF-κB/p65, TNF-α and IL-1β, and the mRNA of NF-κB, TNF-α and IL-1β in the high, middle and low dose of Naoshuming decoction groups were reduced at 3, 7 and 14 d, with statistical difference (all P<0.05 or P<0.01). 
 Conclusion: Naoshuming decoction can alleviate the cerebral ischemic injury in rats.
Animals ; Brain Ischemia ; Infarction, Middle Cerebral Artery ; Inflammation ; Interleukin-1beta ; NF-kappa B ; Rats ; Tumor Necrosis Factor-alpha

Objective To evaluate the safety and clinical efficacy of the treatment for symptomatic uterine fibroids with MR guided focused ultrasound surgery(MRgFUS)in China. Methods Twenty five selected patients with symptomatic uterine fibroids underwent MRgFUS treatment in our perspective clinical study. Immediately after treatment the patients accepted pelvic enhanced MRI scans, and recorded the non-perfused volume(NPV)and calculated the non-perfused volume ratio(NPV%). We recorded the symptom severity score(SSS) and standard SSS change(ΔSSS)of the patients before, during and 1 week after treatment together with 1, 3, 6, 12 months and several years follow-up. The patients accepted pelvic enhanced MRI scans in the follow-up of 12 months after treatment,and recorded the volume and the volume change(ΔV) of fibroids. We observed the adverse reactions during the treatment and the follow-ups. Wilcoxon test or t test and Pearson or Spearman correlation analysis were used to analyze the data. Results Totally 31 fibroids of 25 patients were completed the treatment. Twenty two patients completed the 12 months follow-up and 15 patients completed the long-term follow-up which was during 34 to 66 months, median follow-up duration was(55 ± 11)months. The NPV was 4.5 to 295.0 cm3, median was 37.0 cm3. The NPV%was 6%to 94%, average was(64 ± 23)%. According to our follow up, the standard SSS continued to decline. Compared with screening standard SSS, all the follow-up standard SSS had significant difference(P<0.05), except for that of the first week. Among all the follow up, only the standard SSS change of 1 week after the treatment had a correlation with NPV%(r=0.552,P=0.005), and the others had no significant correlation with NPV%(P>0.05). The uterine fibroids volume decreased in the 12 months follow-up, which had a significant difference with the volume before treatment(P<0.05). And there was also correlation between the fibroids volume change and NPV(r=0.587,P=0.017). There was no correlation between the volume or volume change and standard SSS or standard SSS change(all P>0.05). None serious adverse effects occurred in all cases. Conclusion MRgFUS is a safe and effective way to treat uterine fibroids.

As a cavola marker protein, caveolin-1 participates in many pathophysiological processes through its scaffolding domain oligomering many celular signal transduction molecules, and also regulates inflammation after cerebral ischemia through different pathways. This article reviews advances in caveolin-1 and inflammation after ischemic stroke in recent years, mainly focusing on its mechanism in regulating inflammation.