Evaluation on Killing Effects of Sensitive Plant Growth Inhibitors on Eupatorium adenophorum

[Objective] Considering invasion of Eupatorium adenophorum, a growth in-hibitor of the plant was developed based on plant sensitivity, to make evaluation on control effects and to determine the optimal concentration. [Method] According to field test method, the effects of treatments with growth inhibitor at 0.5%, 1%, 1.5%and 2% on Eupatorium adenophorum were explored and the growth of other weeds was observed to research selectivity of plant inhibitor on the plant. [Result] The growth inhibitor had significant effects on ground parts of Eupatorium adenophorum. Specifical y, after 2 h, Eupatorium adenophorum was damaged seriously and the damage degree went worse upon inhibitor concentration. After 5 d, the control effect of the inhibitorreached 41.5% with concentration at 1.5%, reached 90.2% with the concentration at 1%, and 100% with the concentration at 1.5% and 2%. After 15 d, the control effect achieved 64.6%, 91.7%, 98.9% and 100% with concentrations at 0.5%, 1%, 1.5% and 2%. Stil , the effects of growth inhibitors on root system were limited. For example, new branches would grow from base part if the inhibitor con-centration is too low. On the other hand, the growth inhibitor is of sensitivity and selectivity, which would not hurt other plants. [Conclusion] It is feasible to rapidly control growth and development and even kil Eupatorium adenophorum based on plant sensitivity and it is proved that the growth inhibitor at 1.5% would considerably restrict and kil Eupatorium adenophorum. Therefore, the concentration of growth in-hibitors should be over 1.5%.

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Tyrosine kinase inhibitors(TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors(GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence-and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

Effectiveness of inhibitors in increasing chloride threshold value for steel corrosion

This investigation was aimed at evaluating the effectiveness of corrosion inhibitors in increasing the chloride threshold value for steel corrosion. Three types of corrosion inhibitors, calcium nitrite （Ca（NO2）2）, zinc oxide （ZnO）, and N,N＇-dimethylaminoethanol （DMEA）, which respectively represented the anodic inhibitor, cathodic inhibitor, and mixed inhibitor, were chosen. The experiment was carried out in a saturated calcium hydroxide （Ca（OH）2） solution to simulate the electrolytic environment of concrete. The inhibitors were initially mixed at different levels, and then chloride ions were gradually added into the solution in several steps. The open-circuit potential （Ecorr） and corrosion current density （lcorr） determined by electrochemical impedance spectra （EIS） were used to identify the initiation of active corrosion, thereby determining the chloride threshold value. It was found that although all the inhibitors were effective in decreasing the corrosion rate of steel reinforcement, they had a marginal effect on increasing the chloride threshold value.

Cytomegalovirus colitis in a patient with Behcet’s disease receiving tumor necrosis factor alpha inhibitory treatment

Anti-tumor necrosis factor alpha (TNF-α) inhibitors are effective in the treatment of various inflammatory rheumatic conditions. Increased risks of serious infections are the major issues concerning the long-term safety of these agents. We present a case of a young male Behcet’s patient whose disease was complicated by cytomegalovirus (CMV) colitis. Colitis started 10 d after the third Infliximab dose and responded to the cessation of TNF blocking treatment and administration of ganciclovir. Tumor necrosis factor alpha and interferon gamma act at several levels in combating viral infections.CMV infections should be kept in mind and included in the differential diagnosis of severe gastrointestinal symptoms in patients receiving anti-TNF agents.

Cytotoxic effect of a non-peptidic small molecular inhibitor of the p53-HDM2 interaction on tumor cells

AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China(RWE-PCSK study)

BACKGROUND The efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease(ASCVD).METHODS This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention(PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events(MACE) over six months were compared between two groups.A propensity score-matched(PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.RESULTS In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol(LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81%(P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group(P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE(hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250).CONCLUSIONS In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival

BACKGROUND Despite the popularity of immune checkpoint inhibitors(ICIs)in the treatment of advanced cancer,patients often develop gastrointestinal(GI)and non-GI immune-related adverse events(irAEs).The clinical characteristics and survival outcomes of GI-irAEs have not been fully elucidated in previous reports.This necessitates the evaluation of the impact of GI-irAEs on patients receiving ICI treatment.AIM To evaluate the clinical characteristics of GI-irAEs and their impact on survival in patients treated with ICIs.METHODS In this single-center,retrospective,observational study,we reviewed the records of 661 patients who received ICIs for various cancers at Nagoya University Hospital from September 2014 to August 2020.We analyzed the clinical characteristics of patients who received ICI treatment.We also evaluated the correlation between GI-irAE development and prognosis in non-small cell lung cancer(LC)and malignant melanoma(MM).Kaplan-Meier analysis was used to compare the median overall survival(OS).Multivariate Cox proportional hazards models were used to identify prognostic factors.A P value<0.05 was considered statistically significant.RESULTS GI-irAEs occurred in 34 of 605 patients(5.6%)treated with an anti-programmed cell death-1/programmed death-ligand 1(anti-PD-1/PD-L1)antibody alone and in nine of 56 patients(16.1%)treated with an anti-cytotoxic T-lymphocyte antigen 4(CTLA-4)antibody alone or a combination of anti-PD-1 and anti-CTLA-4 antibodies.The cumulative incidence and median daily diarrhea frequency were significantly higher in patients receiving anti-CTLA-4 antibodies(P<0.05).In 130 patients with MM,OS was significantly prolonged in the group that continued ICI treatment despite the development of GI-irAEs compared to the group that did not experience GI-irAEs(P=0.035).In contrast,in 209 patients with non-small cell LC,there was no significant difference in OS between the groups.The multivariate analyses showed that a performance status of 2-3(hazard ratio:2.406;95%confidence interval:1.125–5.147;P=0.024)was an independent predictive factor for OS in patients with MM.CONCLUSION Patients receiving anti-CTLA-4 antibodies develop GI-irAEs more frequently and with higher severity than those receiving anti-PD-1/PD-L1 antibodies.Continuing ICI treatment in patients with MM with GI-irAEs have better OS.

Choroidal thickening with serous retinal detachment in BRAF/MEK inhibitor-induced uveitis:A case report

BACKGROUND Immune checkpoint inhibitors have revolutionized the treatment of patients with unresectable metastatic malignant melanoma.In addition to systemic side effects,several usually mild ocular adverse effects have been reported.We report a case of rarely reported vision-threatening bilateral panuveitis with serous retinal detachment,thickened choroid,and chorioretinal folds associated with dabrafenib and trametinib targeted therapy for B-Raf proto-oncogene serine/threonine kinase(BRAF)mutant metastatic cutaneous melanoma.CASE SUMMARY A 59-year-old female patient with metastatic melanoma treated with dabrafenib and trametinib presented with blurry vision and central scotoma lasting for 3 d in both eyes.Clinical examination and multimodal imaging revealed inflammatory cells in the anterior chamber,mild vitritis,bullous multiple serous retinal detachments,and chorioretinal folds in both eyes.Treatment with dabrafenib and trametinib was suspended,and the patient was treated with topical and intravenous corticosteroids followed by oral corticosteroid treatment with a tapering schedule.One and a half months after the disease onset,ocular morphological and functional improvement was noted.Due to the metastatic melanoma dissemination,BRAF/mitogen-activated protein kinase inhibitors were reintroduced and some mild ocular adverse effects reappeared,which later subsided after receiving oral corticosteroids.CONCLUSION Patients on combination therapy with dabrafenib and trametinib may rarely develop severe bilateral panuveitis with a good prognosis.Further studies have to establish potential usefulness of ophthalmological examination for asymptomatic patients.Furthermore,appropriate guidelines for managing panuveitis associated with dabrafenib and trametinib should be established.

The Benefits of SGLT2 Inhibitors in Cardiovascular Prevention, Glycemic Control and Weight Loss, in the Treatment of Diabetes

The sodium and glucose co-transporter inhibitors type 2 (SGLT2) comprises a new class of hypoglycemic drugs to control type 2 diabetes mellitus, in an attempt to add new non-existing benefits to the so far arising classes. Regarding this new class of drugs, represented by dapaglifozin, canaglifozin and empaglifozin, it is important to highlight the benefits brought by these medications to combat hyperglycemia with insulin-independent mechanisms that are beyond glucose reduction, such as cardiovascular events prevention, reduction in HbA1c, weight loss and blood pressure lowering. Recently, a relevant study (Empa-Reg) brought hope and set the spotlight on the prevention of cardiac events among diabetic patients, which is the main cause of mortality within this group. However, despite coming out as a good treatment option, SGLT2 inhibitors are under constant clinical research and, as a new drug, it should be carefully carried out regarding the long-term effects of glycosuria and other possible side effects, such as the observed increase in the incidence of bladder, breast cancer and bone fractures, which require further studies. Therefore, these compounds might represent a landmark approach for the treatment of diabetes.

Analysis of inhibition of concrete steel-rebar corrosion by Na_2Cr_2O_7 concentrations:Implications for conflicting reports on inhibitor effectiveness

Corrosion test data were measured using non-destructive electrochemical techniques and analysed for studying inhibition effectiveness by different concentrations of NazCr207 on the corrosion of concrete steel-rehar in NaC1 and in H2SO4 media. For these, specifications of ASTM G16-95 R04 were combined with the normal and the Gumbel probability density functions as model analytical methods for addressing issues of conflicting reports of inhibitor effectiveness that had generated concerns. Results show that reinforced concrete samples admixed with concentrations having 4 g （0.012 7 tool）, 8 g （0.025 4 mol） and 6 g （0.019 l tool） NaaCr207 exhibited, in that order, high inhibition effectiveness, with respective efficiency, r/, of （90.46±1.30）%, （88.41＋2.24）% and （84.87±4.74）%, in the NaC1 medium. These exhibit good agreements within replicates and statistical methods for the samples. Also, optimal inhibition effectiveness model in the H2SO4 medium was exhibited by 8 g （0.025 4 mol） Na2Cr207 concentration having r/=（78.44±1.10）%. These bear implications for addressing conflicting test data in the study of effective inhibitors for mitigating steel-rebar corrosion in aggressive environments.

Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest

AIM: To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. METHODS: Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry.RESULTS: The proliferation of gastric carcinoma cells was inhibited by PBA in a doseand time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G0/G1 phase, whereas cells treated with high concentrations of PBA were arrested at the G2/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G0/G1 phase, cells treated with high concentrations of PBA were arrested at the S phase. CONCLUSION: The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and G2/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G0/G1 and S phases.

Immune blockade inhibitors and the radiation abscopal effect in gastrointestinal cancers

The field of tumor immunology has produced in the recent years a revolution in cancer therapeutics putting an end in the long lasting frustration of investigators in the area stemming from largely unsuccessful strides to develop cancer vaccines. This progress has come from the introduction of immune checkpoint inhibitors, monoclonal antibodies blocking ligand/receptor pairs with inhibitory effects for immune cells. Through this blockade immune checkpoint blockers are able to ac-tivate the immune system and create an anti-tumoral effect. A significant sub-set of patients with various types of cancers such as melanoma, lung carcinomas and urothelial cancers benefit from treatment with these drugs and survivals have improved in some ca-ses. However other cancers are primarily resistant to immune blockers and secondary resistance is also the norm. Radiation therapy is often used in the palliative treatment of patients with advanced cancers and, in addition to the local effect in the irradiated field, it may in rare cases produce a systemic antitumor effect, termed "abscopal". This effect has been suggested to be produced by immune mechanisms. Thus an opportunity presents for a synergistic effect of immune stimulation between radiation and immune blockade inhibitors. The therapeutic opportunities presented with the combination of radiation and these drugs for gastrointestinal cancers will be discussed in this editorial overview.

Antithrombotic effects of bromophenol,an alga-derived thrombin inhibitor

Thrombin,the ultimate proteinase of the coagulation cascade,is an attractive target for the treatment of a variety of cardiovascular diseases.A bromophenol derivative named (+)-3-(2,3-dibromo-4,5-dihydroxy-phenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroiso-benzofuran 1,isolated from the brown alga Leathesia nana exhibited significant thrombin inhibitory activity.In this study,we investigated the inhibition of human thrombin in vitro with this bromophenol derivative,and its antithrombotic efficacy in vivo using the arteriovenous shunt model and the ferric chloride-induced arterial thrombosis model in rats.The results show that the bromophenol derivative is a potential inhibitor of thrombin (IC50=1.03 nmol/L).In antithrombotic experiments in vivo,the bromophenol derivative also shows good effect comparing with the control group.These data indicate that the bromophenol derivative is a potential drug for prophylaxis and the treatment of thrombotic diseases.

Aspects of Antithrombotic Effect of HMG-CoA Reductase Inhibitors

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hypercholesteremia and have showed remarkable activity in preventing cardiovascular morbidity and mortality. Recent studies demonstrated that statins have significant antithrombotic effect in addition to cholesterollowering action. Although the efficacy of statins for reducing cardiovascular events has historically been ascribed to their inhibitory activity on cholesterol synthesis, the degree of low-density lipoprotein cholesterol reduction by statins generally does not correlate with the magnitude of coronary risk reduction.

Triterpenoids from Uncaria rhynchophylla and Their PTP1B Inhibitory Activity

Uncaria rhynchophylla(Gouteng)is a famous traditional Chinese medicine used for psychiatric and hypotensive purposes in China.In this study,the ethyl acetate(EtOAc)part of U.rhynchophylla was revealed with protein tyrosine phosphatase 1B(PTP1B)inhibitory activity.Subsequent investigation on the EtOAc part yielded one new triterpenoid,3β-formyloxy-6β,19α-dihydroxyurs-12-en-28-oic acid(1)and four known ones,3β,6β,19α-trihydroxyurs-12-en-28-oic acid(2),2-oxopomolic acid(3),3β,19α-dihydroxy-6-oxo-olean-12-en-28-oic acid(4)and sumaresinolic acid(5).The structure of compound 1 was determined by extensive HRESIMS,IR,1D and 2D NMR spectroscopic analyses.Two ursane-type triterpenoids(2 and 3)showed selective inhibition on PTP1B with IC50 values of 48.2 and 178.7μM.The enzyme kinetic study suggested that compounds 2 and 3 were mixtype inhibitors on PTP1B with Ki values of 15.6 and 132.5μM.This investigation manifests the antidiabetic potency of U.rhynchophylla with triterpenoids as the active constituents.

Tyrosine Kinase Inhibitors against Cancer: Their Safety in 216 Moroccan Patients

Tyrosine kinase inhibitors (TKIs) have become a prominent option in the therapeutic arsenal of several cancers. The safety of these drugs has shown various toxicities with varying frequency and severity between different agents. The aim of this study is to describe the safety profile of different classes of TKI used in various solid tumors. It is a retrospectively descriptive study conducted in the Department of Medical Oncology at Hassan II University Hospital of Fez, Morocco, over a period of 6 years from April 2013 until April 2019. It included 216 patients who received one or more TKI for different indications in solid tumors. The average age in our series was 61.4 years with a sex ratio F/M of 1.07. Among the most used TKIs in our department according to their availability: Imatinib (32%) and sunitinib (32%). All patients received one or more tyrosine kinase inhibitors according to the indication. Kidney cancer was the most common malignancy (36%), followed by gastrointestinal stromal tumors (33%). The median duration of treatment was 15 months with extremes of 1 month and 102 months. The main side effects were: Cutaneous in 43% of patients. Digestive toxicity occurred in 36% of cases. Hematotoxicity was reported in 33% of cases. The safety profile of TKIs used in our study was comparable to their global tolerance reported in literature. More studies are needed to investigate the relationship between their toxicity and their efficacy in Moroccan population.

EFFECTS OF BLEOMYCIN A5 COMBINED WITH CALMODU-LIN INHIBITOR ON THE PROLIFERATION OF S-180 CELLS IN VITRO

The effects of bleomycin A5 (BLM A5) alone and combined with calmodulin inhibitor N-(4-aminobutyl)-5-chloro-2-naphthalene sulfonamide (W-13) on the proliferation on S-180 cells in vitro were studied. IC50 of BLM used alone for the cells was about 2.63 μg/ml, but it was reduced to 1/3.8 and 1/9.5 of 2.63 μg/ml when plus W-13 1, 5 μg/ml respectively. The results indicated that nontoxic doses of W-13 enhanced the hinibition of cell proliferation under the condition of BLM 0.5 - 2.5 μg/ ml. In colony forming test, the survival fraction of S-180 cells treated with BLM plus W-13 was decreased to 1/87 - 240 of that of the cells treated with BLM alone. The results suggest that W-13 can enhance antitumor activity of BLM in vitro and may be used as an synergist of BLM A5 in vivo.

Effect of nitric oxide synthase inhibitor N^G-nitro-L-arginine on the content of amino acid in ischemic brain tissues of rats

BACKGROUND： Nitric oxide synthase （NOS） inhibrtors have been widely used to investigate the role of NO on cerebral ischemic injury, but the results are controversial. Moreover, it has been considered to aggravate the ischemic neuronal damage with the release of excessively excitatory amino acids （EAA） during cerebral ischemia. On the other hand, some inhibitory amino acid is suggested to be important for the neuronal protection against ischemic brain damage. Our study has recently showed that treatment with the NOS inhibitor NG-nitro-L-arginine （L-NA） reduced focal cerebral ischemic damage. The effect of L-NA on the contents of excitatory and inhibitory amino acid in the rat brain following cerebral ischemia is still unclear. OBJECTIVE： By evaluating the effect of NOS inhibitor, L-NA on the contents of aspartate, glutamate, glycine and γ-aminobutyric acid （GABA） in striatum, hippocampus and cortex in the rat brain following cerebral ischemia respectively, to investigate the beneficial effect of L-NA on cerebral ischemic injury and the possible mechanism. DESIGN： A randomized and controlled experiment SETTING ： Department of Pharmacology, Hebei Academy of Medical Sciences MATERIALS： A total of 42 male healthy SD rats （grade Ⅱ, weighting 250-300 g） were provided by the Experimental Animal Center of Hebei Province （Certification： 04036）. Aspartate, glutamate, glycine, GABA, L-NA and 2,3,5-triphenyltetrazolium chloride （TTC） were obtained from Sigma Chemicals Co, St Louis, MO, USA. HPLC-ultraviolet detector system consisted of Agilent 1100 HPLC. METHODS： The experiment was carried out in Department of Pharmrcology, Hebei Academy of Medical Sciences from June 2005 to June 2006. Rats were randomly divided into three groups： sham-operated group （n = 6）, ischemic group （n = 18）, L-NA group （n = 18）. The model of focal cerebral ischemia in rat was prepared with intraluminal line occlusion methods. In sham-operated rats, the external carotid artery was surgically prepared, but the filament was not inserted. Each group was further divided into 3 subgroups （n = 6 for each）： drugs were administrated at 2, 6 and 12 hours after the middle cerebral artery occlusion （MCAO） respectively. L-NA （20 mg/kg, ip） was administrated, twice a day, for 3 consecutive days. Same volume of normal saline was administrated in ischemic and sham operation groups. The changes of infarcted volume and the contents of amino acids were respectively assayed. Image analysis software was used for the measurement of the infarcted area. The results were expressed as a percentage of the infarcted volume of cerebral/volume of whole brain （IV%） in order to control for edema formation. The contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in the rat brain following cerebral ischemia were respectively measured by HPLC method. All data were analyzed with one-way ANOVA and Dunnett＇s test. MAIN OUTCOME MEASURES： （1） The volume of cerebral infarction; （2） The contents of aspartate, glutamate glycine and GABA in brain tissue after cerebral ischemia. RESULTS ： All 42 rats were involved in the final analysis. （1） Infarcted volume： Volume was 0 in sham-operated group. When L-NA was administrated at 2 and 6 hours after MCAO, the infarcted volume was （20.13±3.59）% and （23.12±5.84）% in L-NA group, which was not similar to that in ischemic group [（22.10±3.98）%, （25.38± 5.37）%, P〉 0.05]. However, the infarcted volume was markedly decreased compared with that of ischemic group when L-NA was administrated at 12 hours after MCAO [（26.11±3.55）% and （37.15±3.58）%, P 〈 0.01]. Changes of amino acid content： At 2 and 6 hours after ischemia, the contents of aspartate, glutamate, glycine and GABA in striatum, hippocampus and cortex in ischemic group were significantly increased compared with those in sham-operated group （ P〈 0.05-0.01）. However, contents in L-NA group were similar to those in ischemic group （P 〉 0.05）. At 12 hours after ischemia, the contents of aspartate [（0.21 ±0.06）, （0.36±0.05）, （0.29±0.12） mg/g] and glutamate [（0.55±0.06）, （0.78±0.10）, （0.52±0.10） mg/g] in striatum, hippocampus and cortex in L-NA group were significantly decreased compared with those in ischemic group [（0.49±0.17）, （0.63± 0.03）, （0.51±0.15） mg/g; （0.98±0.30）, （1.15±0.15）, （0.93±0.15） mg/g, P〈 0.05-0.01]. Glycine in hippocampus was （0.40±0.07） mg/g, which was higher than that in ischemic group [（0.21±0.07） mg/g, P 〈 0.05]. GABA in striatum, hippocampus and cortex was （0.93±0.10）, （0.62±0.12） and （0.81 ±0.10） mg/g, respectively, which was higher than that in ischemic group [（0.60±0.08）, （0.37±0.17）, （0.59±0.10） mg/g, P 〈 0.05-0.01]. CONCLUSION ： It may be concluded that L-NA have beneficial effect on ischemic cerebral injury in ischemic later stage in rats. The possible mechanism is that L-NA can decrease the contents of aspartate and glutamate, increase the contents of glycine and GABA.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis

Immune-checkpoint inhibitor-mediated colitis(IMC)is an increasingly recognized adverse event in cancer immunotherapy,particularly associated with immune checkpoint inhibitors(ICIs)such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies.As this revolutionary immunotherapy gains prominence in cancer treatment,understanding,diagnosing,and effectively managing IMC becomes paramount.IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications.However,a precise picture of IMC pathophysiology is currently unavailable.Therefore,we aimed to summarize the existing data while acknowledging the need for further research.This comprehensive review explores the mechanisms underlying ICIs,gastrointestinal adverse effects,and,in particular,IMC’s incidence,prevalence,and features.Our review also emphasizes the importance of recognizing IMC’s distinct clinical and histopathological features to differentiate it from other forms of colitis.Furthermore,this paper highlights the urgentneed for evolving diagnostic methods,therapeutic strategies,and a multidisciplinary approach to effectively manage IMC.