Objective: To study the effects of IL-2 and IL-15 on the expression of NKG2D and the cytotoxicity of edited-NK cells against human nasopharyngeal carcinoma cell line CNE2.Methods: NK cells were purified by anti-CD56 MACS and were divided into four groups: non-edited-NK cells group(NK cells treated with 100 U/ml IL-2),edited-NK cells group(NK cells co-cultured with CNE2 cells at a ratio of 10∶1 and then treated with 100 U/ml IL-2),edited-NK cells retreated with 1 000 U/ml IL-2 group,and edited-NK cells retreated with 10 ng/ml IL-15 group.Expression of NKG2D in each group was determined by FACS 24 h later.Cytotoxicity of NK cells against CNE2 cells(NK∶CNE2 being 20∶1) was measured by LDH releasing assay.Results: The expression of NKG2D in non-edited-NK cells,edited-NK cells,edited-NK cells retreated with IL-2,and edited-NK cells retreated with IL-15 were(97.63?0.83)%,(53.50?1.25)%,(94.47?1.00)%,and(98.07?0.21)%,respectively.The expression of NKG2D on edited-NK cells retreated with IL-2 or IL-15 was significantly increased than that on edited-NK cells(P

Phosphodiesterase-4 ( PDE4 ) has been one of the most popular drug targets during recent years due to its critical role in the control of intracellular cyclic adenosine monophos-phate ( cAMP ) concentration and downstream signal transduc-tion. PDE4 is widely distributed in the central nervous system ( CNS) with different expression levels of its four subtypes. Re-cent data indicate that altered PDE4 expression and/or activity is relevant to multiple CNS disorders, such as depression, memory deficiency, drug dependence, and neural lesion. Selective PDE4 inhibitors exhibit therapeutic effects on these disorders and might be a promising pharmacotherapy. The paper highlights recent re-search progress in the roles of PDE4 in CNS function, and dis-cusses the prospects of PDE4 as a novel therapeutic target for CNS disorders.

Venous thromboembolism(VTE)is a prevalent complication in orthopedics.In recent years,machine learning has been widely applied in orthopedics.The essence of machine learning lies in utilizing algorithms to analyze vast amounts of data and construct risk prediction models that can accurately forecast unknown clinical outcomes.By integrating high-risk factors,machine learning aids medical professionals in precisely identifying and screening individuals with a high risk of VTE and offering them timely individualized interventions.This article reviews the concept and classification of machine learning,the advantages of machine learning in enhancing model prediction ability,and the current application status of machine learning in constructing risk prediction models for patients with VTE.

OBJECTIVE To explore the distribution pattern of traditional Chinese medicine(TCM)syndrome types of primary o-varian insufficiency(POI)sleep disorders and the differences in the distribution of sleep quality index among different syndrome types,in order to provide a basis for syndrome differentiation treatment and prevention of POI associated with sleep disorders.METHODS 600 POI patients who met the inclusion criteria were collected for epidemiological investigation,and 405 patients who met the diagnosis of sleep disorders were selected as the research group.The patients'general information,TCM four diagnosis and sex hormone level in-formation were collected,and the Pittsburgh sleep quality index(PSQI)scale was used to evaluate patients'sleep conditions,and ana-lyze the characteristics and influencing factors of TCM syndrome types of POI associated with sleep disorders.RESULTS The main TCM syndrome types of POI accompanied by sleep disorders were heart and kidney disharmony syndrome(41.98%),spleen and kid-ney yang deficiency syndrome(22.22%),kidney deficiency and liver stagnation syndrome(20.99%),and kidney deficiency and blood stasis syndrome(14.81%).The heart and kidney disharmony syndrome had the longest sleep latency and shortest sleep time,relied more on hypnotic drugs,and had the highest PSQI total score;the heart and kidney disharmony syndrome and kidney deficiency and liver stagnation syndrome had the worst sleep quality;the spleen kidney yang deficiency syndrome had the highest daytime dysfunc-tion score.There was no significant difference in FSH levels among different TCM syndrome types;the distribution of E2 values from low to high was:heart and kidney disharmony syndrome,kidney deficiency and liver stagnation syndrome,spleen and kidney yang de-ficiency syndrome,and kidney deficiency and blood stasis syndrome,and there were significant differences among multiple groups(P<0.05).CONCLUSION The main TCM syndrome types of patients with POI and sleep disorders are heart and kidney disharmony syn-drome,spleen and kidney yang deficiency syndrome,kidney deficiency and liver stagnation syndrome,and kidney deficiency and blood stasis syndrome.Among them,the most common TCM syndrome type with the worst sleep quality is heart and kidney disharmony syn-drome,which may be closely related to estrogen E2 levels.

AIM:To explore the impact of histidine triad nucleotide-binding protein 2(HINT2)on atheroscle-rosis(AS),and to elucidate its underlying mechanisms.METHODS:Peripheral blood mononuclear cells(PBMCs)were isolated from patients with chest pain and induced to differentiate into macrophages for assessing HINT2 expression.In vitro,RAW264.7 mouse macrophages were cultured to evaluate inflammatory cytokine levels and cell death in superna-tants.An apolipoprotein E gene knockout(apoE-/-)mouse model of AS was developed to analyze plaque formation,lipid metabolism and macrophage foaminess in the aortic root.Pyroptosis-related protein expression in cultured RAW264.7 cells and the aorta of apoE-/-mice was determined by RT-qPCR and Western blot.RESULTS:Significantly reduced HINT2 expression was observed in PBMCs from patients with acute coronary syndrome,which was negatively correlated with pro-inflammatory and positively correlated with anti-inflammatory serum factors,suggesting HINT2's potential role in mitigating AS-related inflammation.In vitro experiments demonstrated that HINT2 overexpression inhibited lipid accumu-lation and foam cell formation in macrophages induced by oxidized low-density lipoprotein(ox-LDL).It also reduced se-cretion of inflammatory cytokines,including interleukin-6(IL-6),IL-1β,IL-18 and tumor necrosis factor-α,and de-creased cell death and pyroptosis-related protein expression.In vivo experiments in apoE-/-mice confirmed that HINT2 overexpression lessened plaque burden in the aortic root,reduced macrophage foaminess,and inhibited the expression of pyroptosis-related proteins such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),IL-1β and IL-18.CONCLUSION:HINT2 potentially inhibits ox-LDL-induced macrophage pyroptosis,attenuates inflammatory responses in AS,and may slow the progression of this disease.

OBJECTIVE：To i nvestigate the clini cal ch aracteristics of anaphylactic shock induced by piperacillin and its compound preparation ，and to provide reference for prevention and treatment of the severe ADR. METHODS ：A case of anaphylactic shock induced by piperacillin and sulbactam were analyzed in our hospital ，meanwhile ADR literatures about piperacillin alone and its compound preparation-induced anaphylactic shock were collected from Medline ，CNKI，Wanfang database and VIP during the inception to Jul. 2020. Gender and age of patients ，allergic history ，primary disease and treatment ，skin test ， administration route and dosage of piperacillin and its compound preparation ，occurrence time and main manifestations of anaphylactic shock ，treatment measure and prognosis were analyzed ，then prevention and treatment suggestions were put forward. RESULTS：The patient in this case was transferred to the ICU after partial hepatectomy. The use of piperacillin and sulbactam to prevent postoperative infection caused anaphylactic shock. A total of 28 literatures about anaphylactic shock induced by piperacillin and its compound preparations were collected from the database （involving 28 patients）. Among totally 29 patients，there were 12 male and 17 female；the majority of patients were 50-59 years old （6 cases，20.69％）. Three patients had allergic history （food， latex gloves ，etc.），and most of the primary diseases were infectious diseases or the drug used in perioperative period. Skin tests were carried out in 22 patients（75.86％）before medication and the results were negative. The possible allergenic drugs of 27 cases which were administered by intravenous route included piperacillin ，piperacillin sulbactam and piperacillin tazobactam. The dosage was different according to the primary disease and severity. 14 patients（55.56％）developed anaphylactic shock within 5 minutes after drug exposure. The main symptoms were systemic allergic reaction ，mainly involving the circulatory system. Except for two death cases ，the other patients ’symptoms were relieved after treatment. CONCLUSIONS ：Allergic history and skin test results may have limitation in predicting anaphylactic shock induced by piperacillin and its compound preparation. Close monitoring needs to be taken in patients during these medications. Rescue therapy should be prepared in advance and countermeasures need to be carried out promptly in case of anaphylactic shock.