Analysis of the Necessity of Stellate Ganglion Block after Anesthesia to Reduce the Risk of Cardiovascular Accidents in Coronary Heart Disease

Objective:To adjust the sympathetic nervous system through preoperative ultrasound-guided stellate ganglion block and to explore and analyze the situation and necessity of postanesthesia stellate ganglion block to reduce the risk of cardiovascular accidents in coronary heart disease.Methods:80 patients with cardiovascular risk factors in Songshan Hospital of Chifeng were selected,and the time span would cover from October 2022 to June 2024,with 80 cases of elective surgery and combined coronary heart disease.They will be randomly divided into blocked groups and conventional groups,40 cases each.Conventional block was performed after anesthesia in patients in the conventional group,and planetary ganglion block was performed after anesthesia in patients in the blocked group.The cardiovascular responses of patients in the two groups were observed,and the number of intraoperative cardiovascular active drugs and the occurrence of cardiovascular adverse events were recorded in patients in the two groups.Results:Analysis of the mean arterial pressure(MAP)and heart rate(HR)values of the two groups of patients at the time points before anesthesia(T0),the moment of tracheal intubation(T1),the moment of surgical skin cutting(T2),the end of the operation(T3),and the 6h postoperative period(T4)showed that the MAP and HR of the blocked group were lower than those of the conventional group at the time points of T1 to T4,and the differences in MAP and HR values of the two groups in different time points compared with the T0 time point were statistically significant(P<0.05)and the differences in cardiovascular response(P<0.05)were statistically significant(P<0.05).significance(P<0.05).The number of intraoperative cardiovascular active drugs used in the blocked group was shorter than that in the conventional group,and the incidence of cardiovascular adverse events was lower than that in the conventional group,with a statistically significant difference(P<0.05).Conclusion:By implementing preoperative ultrasound-guided stellate ganglion block in patients with cardiovascular risk factors,the frequency and degree of coronary heart disease symptoms will be reduced,thus reducing the risk of patients,which is worth promoting.

Treatment and surveillance for non-muscle-invasive bladder cancer:a clinical practice guideline(2021 edition)

Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.

Therapeutic effects and safety of olcegepant and telcagepant for migraine A meta-analysis

OBJECTIVE： To evaluate the therapeutic effects and adverse reactions of olcegepant and telcagepant for the treatment of migraine. DATA RETRIEVAL： We identified studies using Medline （1966-01/2012-06）, PubMed （1966-01/2012-06）, Scopus （1980-01/2012-06）, Cochrane Central Register of Controlled Trials （1980-01/2012-06） and China National Knowledge Infrastructure （1980-01/2012-06）. SELECTION CRITERIA： The included studies were double-blind, randomized and placebo-controlled trials of olcegepant or telcagepant for the treatment of single acute migraine in patients with or without aura. Adverse reaction data were also included. Two independent investigators performed quality evaluation and data extraction using Jadad scoring. Meta-analyses were undertaken using RevMan 5.0.25 software. MAIN OUTCOME MEASURES： Pain relief rate, pain-free rate, and incidence of adverse reactions were measured in patients 2 and 24 hours after injection of olcegepant and oral teicagepant. RESULTS： Six randomized, controlled trials were included. Meta-analysis demonstrated that compared with placebo, the pain relief rate （odds ratio, OR = 5.21, 95% confidence interval, CI： 1.91-14.2, P 〈 0.01） and pain-free rate （OR = 31.11, 95% Ch 3.80-254.98, P 〈 0.01） significantly increased 2 hours after 2.5 mg/d olcegepant treatment. Pain relief rate and pain-free rate 2 and 24 hours after treatment with telcagepant 150 mg/d and 300 mg/d were superior to placebo （P 〈 0.01）. Moreover, the remission rate of unrelenting headache was higher after 24 hours of 300 mg/d telcagepant treatment compared with 150 mg/d （OR = 0.78, 95% Ch 0.62-0.97, P 〈 0.05）. The incidence of adverse reactions with olcegepant was not significantly greater than placebo （P = 0.28） but within 48 hours of administration of telcagepant 300 mg/d, the incidence of adverse reactions was higher than placebo （OR = 1.21,95% Ch 1.04-1.42, P 〈 0.01）. Few studies have compared the therapeutic effects of olcegepant and telcagepant. CONCLUSION： The calcitonin-gene-related peptide receptor antagonists olcegepant and telcagepant have shown good therapeutic effects in the treatment of migraine. Moreover, the incidence of adverse reactions compares favorably with placebo, although liver transaminases may become elevated after long-term use.

Propofol's effect on the sciatic nerve Harmful or protective?

Propofol can inhibit the inflammatory response and reduce the secretion and harmful effects of as-trocyte-derived proinflammatory cytokines. In this study, after propofol was injected into the injured sciatic nerve of mice, nuclear factor kappa B expression in the L 4-6 segments of the spinal cord in the injured side was reduced, apoptosis was decreased, nerve myelin defects were al eviated, and the nerve conduction block was lessened. The experimental findings indicate that propofol inhibits the inflammatory and immune responses, decreases the expression of nuclear factor kappa B, and reduces apoptosis. These effects of propofol promote regeneration fol owing sciatic nerve injury.

Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

Role of penehyclidine in acute organophosphorus pesticide poisoning

BACKGROUND:Penehyclidine is a newly developed anticholinergic agent.We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning(OP)patients.METHODS:We searched the Pubmed,Cochrane library,EMBASE,Chinese National Knowledge Infrastructure(CNKI),Chinese Biomedical literature(CBM)and Wanfang databases.Randomized controlled trials(RCTs)recruiting acute OP patients were identifi ed for meta-analysis.Main outcomes included cure rate,mortality rate,time to atropinization,time to 60%normal acetylcholinesterase(AchE)level,rate of intermediate syndrome(IMS)and rate of adverse drug reactions(ADR).RESULTS:Sixteen RCTs involving 1,334 patients were identifi ed.Compared with the atropineor penehyclidine-alone groups,atropine combined with penehyclidine significantly increased the cure rate(penehyclidine+atropine vs.atropine,0.97 vs.0.86,RR 1.13,95%CI[1.07–1.19];penehyclidine+atropine vs.penehyclidine,0.93 vs.0.80,RR 1.08,95%CI[1.01–1.15])and reduced the mortality rate(penehyclidine+atropine vs.atropine,0.015 vs.0.11,RR 0.17,95%CI[0.06–0.49];penehyclidine+atropine vs.penehyclidine,0.13 vs.0.08,RR 0.23,95%CI[0.04–1.28]).Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery,the rate of IMS and the rate of ADR.Compared with a single dose of atropine,a single dose of penehyclidine also signifi cantly elevated the cure rate,reduced times to atropinization,AchE recovery,and rate of IMS.CONCLUSION:Atropine combined with penehyclidine benefi ts OP patients by enhancing the cure rate,mortality rate,time to atropinization,AchE recovery,IMS rate,total ADR and duration of hospitalization.Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

A Case of a Primary Endodermal Sinus Tumor of the Cerebellar Vermis

A 10-year-old boy appeared with a headache, mainly in the forehead, and with lethargy at noon on November 10, 2004. He reported discontinuous gas pains, no nausea, no vomiting and no blurred vision. He thought that he had a ＂common cold＂, but treatment for 3 days produced no result. He was diagnosed as having viral encephalitis after an examination including an electroencephalogram （EEG）, blood biochemistry and lumbar puncture, etc. in a local hospital on November 15. After further treatment for 3 days his symptoms became aggravated showing instability of gait and involuntary movement of his head and extremities. Cranial CT showed： a 4.0 cm×4.0 cm×5.0 cm lump in the cerebellar vermis which intruded into the fourth ventricle inducing evident distention of the third and lateral ventricle. He was diagnosed with blastoma of the cerebellum.

Effect of Allocryptopine on Late sodium current of atrial myocytes in spontaneously hypertensive rats

Objective To explore the effect of allocryptopine （All） on the Late sodium current （INa,Late） of atrial myocytes in spontaneously hyper- tensive rats （SHR）. Method The enzyme digestion method was used to separate single atrial myocytes from SHR and Wistar-Kyoto rat （WKY） rats. INa,Late was record by patch-clamp technique and the effect of All on the current was evaluated. Results Comparing with WKY cells, markedly increasing of INa,Late current in SHR myocytes was found from 0.24 ± 0.02 pA/pF of WKY cells to 1.73± 0.04 pA/pF of SHR cells （P 〈 0.01, n = 15）. After treament with 30 μmol/L All; the current densities was reduced to 0.92 ± 0.03 pA/pF. The ratio of INa,Late/INa,peak of WKY and SHR were 0.09% ± 0.01% and 0.71% ± 0.02%, INa, Late/INa,peak of SHR was reduced to 0.37% ± 0.02% by 30 μmol/L All （P 〈 0.01, n = 15）. We also determined the effect of All on the gating mechanism of the INa,Late in the SHR cells. It was found that All decreased the INa,Late by alleviating the inactivation of the channels and increasing the window current of sodium channel. Conclusion Increased INa,Late in SHR atrial myocytes and the prolonged APD were inhibited by All coming from Chinese herb medicine.

Meta-analysis of efficacy of topiramate in migraine prophylaxis

OBJECTIVE：To evaluate the treatment effects and safety of topiramate in migraine prophylaxis. DATA RETRIEVAL：We searched the Medline database,EMbase,Cochrane Library and China National Knowledge Infrastructure database for articles published between January 1995 and May 2011,using the key words＂migraine＂,＂topiramate＂,and＂prophylaxis＂. SELECTION CRITERIA：We selected randomized controlled trials of migraine patients,in which the experimental group was orally administered topiramate,and the control group was given placebo. Odds ratios（ORs）and mean differences（MDs）were calculated using a fixed effects model/random effects model.Quality evaluation and data extraction were performed independently by two researchers utilizing RevMan 5.0 software. MAIN OUTCOME MEASURES：Efficacy was recorded as the responder rate（response defined as at least a 50%reduction in average monthly migraine frequency）and change in mean monthly number of migraine days.Adverse events were recorded as the number of subjects exhibiting at least one adverse event. RESULTS：Eight randomized controlled trials were found to be appropriate,and had available data. The meta-analysis results revealed that topiramate（100 or 200 mg/d）was more effective than placebo in responder rate（OR=2.97,95%confidence interval（CI）：2.17-4.08,P〈0.01;OR=2.35, 95%CI：1.77-3.12,P〈0.01）.Topiramate（100 mg/d）was more effective than placebo in terms of the change in mean monthly migraine days（MD：-1.14,95%CI：-1.69 to-0.59,P〈0.01）.The total incidence rate of adverse events for topiramate was higher than in the placebo group（P〈0.01）,but most adverse events were mild to moderate. CONCLUSION：Overall,topiramate obtained good outcomes and safety in migraine prophylaxis.

The Therapeutic Effect of Capecitabine Single Drug Maintenance Therapy in the Advanced Breast Cancer

Objective:To analyze the efficacy of capecitabine(referred to as Cap)single-agent maintenance therapy in the advanced breast cancer.Methods:The subjects of the study were 50 patients with advanced breast cancer who were admitted to our hospital between March 2016 and March 2019.They were divided into groups A and B with 25 cases each.The subjects of these two groups were treated conventional method,respectively.And then,Capecitabine maintenance therapy was continued for group A,clinical observation for groups B.Progressionfree survival(PFS)was compared between the two groups.Results:The median PFS was 14.2 months for group A and 8.9 months for group B(P<0.05).The complication rate of group A was 24.0%compared to that of group B was 22.0%(P>0.05).Conclusion:The patients with advanced breast cancer who received Cap maintenance therapy were benefited from better curative effect and controllable complications,which has high promotion value.

The Description of Pancreatic Cancer Death in Inner Mongolia 2008-2014

Objective: The study aimed to assess the characteristics of pancreatic cancer deaths and the relationship between socio-demographic status and mortality risk of pancreatic cancer in Inner Mongolia. Method: We obtained our data for 2008-2014 from the Death Registry System of Inner Mongolia. We calculated the mortality rate, potential years of life lost (PYLL) and average years of life lost (AYLL) for men and women. We collected socio-demographic characteristics including education level, ethnicity, region, and occupation. Logistic regression models were employed to analyze risk factors of pancreatic cancer. Results: The average mortality rate of pancreatic cancer was 4.42/100,000 in Inner Mongolia during 2008 to 2014. Mortality rate in men was higher in all age groups compared with those in women. The highest mortality rate was 1.3 times than the lowest mortality rate for men and 1.6 times for women during seven years. Average AYLL in women were more than 3.4 years compared with that in men. PYLLR in women was fluctuated from 0.41 to 0.63 per thousand during 2008 to 2014. In eastern region, no occupation and high education level had a higher risk of pancreatic cancer. Conclusion: In Inner Mongolia, the mortality rate associated with pancreatic cancer was higher in men compared with in women. More than 65 years old groups had high death risk for pancreatic cancer. Average years of life lost for women were significantly higher than that for men. We should pay more attention to the older men.

Study on Allergic Rhinitis of Artemisia Sphaerocephala

Objective:To explore the cause and feasibility of Artemisia ordosica allergic rhinitis.Methods:The main allergic causes of allergic rhinitis patients in Chifeng City of inner Mongolia were analyzed by a control method.Results:According to the results,Artemisia ordosica is the most important cause of allergic rhinitis in inner Mongolia.In addition,allergic history,asthma and other diseases,or animal hair and other factors can also increase the risk of patients with allergic rhinitis.Conclusions:Artemisia sphaerocephala is the main cause of allergic rhinitis.In recent years,allergic rhinitis has attracted the attention of international organizations,and the medical community has also studied more methods for the treatment of rhinitis,such as putting forward relevant traditional Chinese medicine(TCM)treatment methods.

Discussion on the Management of Safe Medication in the Treatment of Internal Diseases of Traditional Chinese Medicine

Objective:To discuss the management of safe medication in the treatment of internal diseases in traditional Chinese medicine.Methods:124 patients with medical diseases were divided into experimental group and control group by random number table method,with 62 cases in each group.The experimental group implemented safe medication management,and the control group implemented routine medication management,all of which were treated for 4 consecutive weeks.The comparison of the improvement of the quality of life,the compliance rate of safe medication and the adverse drug reactions of the two groups after clinical treatment were compared.Results:After 8 weeks of treatment,there was a significant difference in clinical efficacy between the two groups of patients.In terms of quality-of-life scores,the scores of the experimental group were better than those of the control group.The living ability,condition,physical strength and other conditions of patients were significantly different.The t-values were 15.3427,14.0275,and 7.7113,respectively,and P<0.01 was statistically significant.The compliance rates of patients in the experimental group and observation group were 95.16%and 70.96%,respectively,with significant differences(P<0.05).In terms of the incidence of adverse drug events,the experimental group was 3.22%,which was significantly lower than the observation group's 8.06%(P<0.05).Conclusion:The implementation of safe medication management in the clinical treatment ofTCM internal diseases can improve the quality of life of patients to a certain extent,increase their safe medication compliance rate,and reduce the incidence of adverse medication events.The clinical application value is extremely high,and it can be widely promoted and applied.

Comparative Analysis on the Curative Effect of Endoscopic Submucosal Dissection and Mucosal Resection in the Treatment of Gastric Neuroendocrine Tumor

Objective:To study the therapeutic effect of endoscopic submucosal dissection and mucosal resection on gastric neuroendocrine tumor.Methods:A hundred patients with gastric neuroendocrine tumor that were treated in the Affiliated Hospital of Chifeng University from January 2016 to May 2021 were randomly selected for this research.They were divided into two groups,which were the control group(endoscopic mucosal resection)and the study group(endoscopic submucosal dissection),by the digital table method.The curative effects of the two groups were observed and compared.Results:Before operation,there were no significant differences in serum CgA,TNF-α,and IL-6 between the two groups,p>0.05.After surgical treatment,the operation time and hospital stay of the patients in the study group were shorter than those in the control group,the amount of surgical bleeding was also less compared to the control group,and the complete tumor resection rate was higher than that in the control group(p<0.05);the levels of IL-6 and CgA of the study group were lower than those in the control group,while the levels of TNF-α were higher than those of the control group,p<0.05;the postoperative complication rate of the study group was lower than that of the reference group(p<0.05).Conclusion:Endoscopic submucosal dissection is more effective for gastric neuroendocrine tumors.The resection rate of the tumor is high,and the operation risk is low.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial

Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.

mTOR Modulates Lymphocyte Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis in Rats

Background： Aspergillosis infection is common in the patients with insufficient immunity. The role of mammalian target of rapamycin （roTOR）, T-box expressed in T-cells （T-bet）, and eomesodermin （EOMES） in mediating T lymphocytes differentiation in response to Aspep,gilhls.fumigatus infection in immunocompromised rats was investigated in this study. Methods： lnvasive pulmonary aspergillosis （IPA） ofimmunosuppressive twenty male rats were established and sacrificed at 24 h （n = 5）, 48 h （n = 5）, 72 11 （n = 5）, and 96 h （n = 5） atter A.Jumigatus infection. In addition, control （n = 5）, cyclophospharnide （CTX） （n = 5）, and aspergillosis （n = 5） group were also established the tissues and pathology of lung tissue was examined by hematoxylin and eosin staining. CD8＋ T-cells was sorted by flow cytometry. Serum roTOR, S6K, T-bet, and EOMES were quantified by enzyme-linked immunosorbent assay. Results： Histology of lung tissue indicated severe lung tissue injury including infiltration of inflammatory cells, alveolar wall damage or degradation, blood congestion, and hemorrhage in the CTX, IPA, and CTX ＋ IPA rats. Hyphae were seen in the IPA, and CTX ＋ IPA groups. The proportion of CD8^＋ T-cells was significantly increased in the animals ofCTX ＋ IPA. Memory CD8＋ T-cells was significantly increased in early stage （24 h and 48 h, P 〈 0.001）, but decreased in the late phase of fungal infection （72 h and 96 h） in the animals of CTX ＋ IPA. In addition, at early stage of fungal infection （24 h and 48 h）, serum mTOR （P 〈 0.001 ）, S6K （P 〈 0.001 ）, and T-bet （P 〈 0.05） was significantly higher, while EOMES was significantly lower （P 〈 0.001 ）, in CTX ＋ IPA group than that in control, CTX alone or 1PA alone group. Conversely, serum roTOR, S6K, T-bet, and EOMES showed opposite changed in the late stage （72 h and 96 h）. Pearson＇s correlation analysis indicated that mTOR and S6K were significantly correlated with T-bet （r = 0.901 and 0.91, respectively, P 〈 0.001 ）, but negatively and significantly correlated with EOMES （r = -0.758 and -0.751, respectively, P 〈 0.001 ）. Conclusions： mTOR may regulate transcription factors of EOMES and T-bet, and by which mechanism, it may modulate lymphocytes differentiation in animals with immune suppression and fungal infection.

A meta-analytic review of ERCC1/MDR1 polymorphism and chemosensitivity to platinum in patients with advanced non-small cell lung cancer

Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer （NSCLC） patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC, we performed a meta-analysis to compare chemosensitivity to platinum with differe4nt ERCC1 Cl18T/ MDR1 C3435T single-nucleotide polymorphism （SNP）. Methods Relevant studies were identified by searching the PubMed, Embase, Cochrane, OVID, Springer, EBSCO and CNKI databases. Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy, an evaluated polymorphism of ERCC/MDIR1 and overall response rate. We excluded duplicate publications, letters and review articles. The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment. Results A total of 11 studies were included in this meta-analysis. For studies evaluating ERCC1 Cl18T, test for heterogeneity was done （X2=13.41, P=0.1）, and the odds ratio （OR） for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 （95% CI 1.09-2.06, P=0.01）. In four studies evaluating MDR1 polymorphism, test for heterogeneity was also done （X2=3.22, P=0.36）, and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 （95% CI 1.44-3.68, P=0.0005）. Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 Cl18T and MDR1 C3435T SNP. In further perspective studies, the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.

Dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and motor neuron loss in the spinal cord of ALS mouse model

Background:Neuron-microglia communication plays a crucial role in the motor neurons(MNs)death in amyotrophic lateral sclerosis(ALS).Neurons can express chemokine(C-X3-C motif)ligand 1(CX3CL1),which mediates microglial activation via interacting with its sole receptor CX3CR1 in microglia.In the present study,we aimed to investigate the dynamic changes of CX3CL1/CX3CR1 axis during microglial activation and MNs loss in SOD1G93A mouse model of ALS.Methods:qPCR,western blot and immunofluorescent staining were used to examine the mRNA and protein levels and localization of CX3CL1/CX3CR1 in the anterior horn region of spinal cord in both SOD1G93A mice and their agematched wild type(WT)littermates at 40,60,90 and 120 days of age.The M1/M2 microglial activation in the spinal cord tissues of SOD1G93A mice and WT mice were evaluated by immunofluorescent staining of M1/M2 markers and further confirmed by qPCR analysis of M1/M2-related cytokines.Results:The immunofluorescent staining revealed that CX3CL1 was predominately expressed in MNs,while CX3CR1 was highly expressed in microglia in the anterior horn region of spinal cord.Compared with age-matched WT mice,CX3CL1 mRNA level was elevated at 40 days but decreased at 90 and 120 days in the anterior horn region of spinal cords in ALS mice.Consistently,CX3CR1 mRNA level was increased at 90 and 120 days.Western blot assay further confirmed the dynamic changes of CX3CL1/CX3CR1 axis in ALS mice.Additionally,the levels of M1/M2 markers of microglia and their related cytokines in the anterior horn region of spinal cord in ALS mice were increased at 90 and 120 days.Moreover,while M1-related cytokines in ALS mice were persistently increased at 120 days,the upregulated M2-related cytokines started to decline at 120 days,suggesting an altered microglial activation.Conclusions:Our data revealed the dynamic changes of CX3CL1/CX3CR1 axis and an imbalanced M1/M2 microglial activation during ALS pathological progression.These findings may help identify potential molecular targets for ALS therapy.

Experimental study on the anti-inflammatory effect of Mongolian medicine Sendeng Decoction on mice with psoriasis

Psoriasis is a chronic papulosquamous skin disease occurring worldwide caused by varieties of factors.The recipe of Mongolian medicine Sendeng Decoction was recorded in“The Pleasure of the Viewer”compiled by Jigwood Danjinzhamusu.Mongolian medicine clinical experience proved that Sendeng Decoction had good antipyretic,analgesic,anti-inflammatory and anti-rheumatism effect.However,the mechanism of this drug in psoriasis is still unclear.In this study,imiquimod cream(IMQ)was used to construct psoriasis model in 8-week-old male BALB/c mice,and Sendeng Decoction was used to treat the mice with psoriasis.The results showed that PASI score and spleen index decreased after Sendeng Decoction treatment.Meanwhile,HE staining showed that the pathological structure was improved,flow cytometry results showed that the proportion of Treg cells increased and Th17 cells decreased,and results of Western blot showed that the level of p38 MAPK,p-p38 MAPK,p-STAT3 and p-JAK1 decreased observably.More importantly,the above results were most significant in Sendeng's M group,which was similar to MTX group.Our results indicated that Mongolian medicine Sendeng Decoction can effectively relieve the symptoms of psoriasis mice induced by IMQ,mainly by regulating the ratio of Th17/Treg cells through the JAK/STAT and p38 MAPK pathways to reduce the inflammatory state in mice,thereby improving the symptoms of dermatitis.

Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer(ESWN 01):a prospective randomized,multicenter,open-labeled phase 3 trial

Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.