OBJECTIVE: To construct a novel fusion protein consisting of oligopeptides specific for human epidermal growth factor receptor 2(HER2) and lidamycin(LDM), and investigate its antitumor activity. METHODS: Coding sequences of oligopeptides from complementarity determining region 3(CDR3) of anti-HER2 antibody C6.5 heavy chain was fused to apoprotein of lidamycin to obtain the fusion gene ldp-Hr. Fusion protein LDP-Hr was expressed in E. coli and purified by affinity chromatography. The purity of LDP-Hr was analyzed by high HPLC. Immunofluorescence assay and flow cytometry-based binding assay were used to investigate the binding activity of LDP-Hr to HER2 overexpressed cancer cells. The energized fusion protein LDP-Hr-AE was prepared by integrating the active enediyne chromophore (AE) of lidamycin into the LDP-Hr protein. MTT assay was used to measure the in vitro cytotoxicity of LDP-Hr-AE and Annexin V-FITC/PI staining assay was used to analyze its apoptosis-inducing efficacy. RESULTS: Fusion protein LDP-Hr was constructed correctly and expressed in E. coli in a secretory manner. The production of LDP-Hr was 40 mg per liter fermentation broth, and the purity of fusion protein was 97.4% as analyzed by HPLC. LDP-Hr showed strong binding activity to cancer cells highly expressing HER2, such as SK-BR-3 and SK-OV-3 cells. The energized fusion protein LDP-Hr-AE exhibited more potent cytotoxicity to SK-BR-3 and SK-OV-3 cells than LDM as measured by MTT assay. The results from Annexin V-FITC/PI staining assay also revealed that LDP-Hr-AE significantly induced cell apoptosis even at very low concentrations. CONCLUSION: The novel energized fusion protein LDP-Hr-AE bounds to HER2 specifically, and shows potent cytotoxicity and apoptosis-inducing activity to cancer cells, which suggests that it would be a promising candidate for targeted cancer therapy.

OBJECTIVE: To construct a novel fusion protein contained insulin-like growth factor 1 (IGF-1) and lidamycin (LDM) and evaluate its antitumor activity on non-small cell lung cancer (NSCLC). METHODS: DNA fragment coding for fusion protein (ldp-igf) was synthesized by linking apoprotein of lidamycin (ldp) with igf-1, and then was cloned into the plasmid pET30a. Fusion protein LDP-IGF was expressed in E.coli as inclusion bodies and was purified by Ni2+ affinity chromatography. Binding affinity of LDP-IGF to NSCLC cells was evaluated by immunofluorescence assay and flow cytometry-based binding assay. MTT assay was used to measure the in vitrocytotoxicity of LDP-IGF and its enediyne-energized analogue LDP-IGF-AE. PI staining assay and Annexin V-FITC/PI staining assay were used to analyze the cell cycle arrest and cell apoptosis after treatment with LDP-IGF-AE, respectively. RESULTS: Active soluble LDP-IGF protein was prepared by isolation, purification, denaturation and refolding, and the production of LDP-IGF was 12 mg per liter fermentation broth. Both of immunofluorescence assay and flow cytometry-based binding assay showed that LDP-IGF has strong binding activity to NSCLC cells. Enediyne-energized fusion protein LDP-IGF-AE exhibited potent cytotoxicity to NSCLC cells in vitro, and it is more potent than that of LDM. Furthermore, fusion protein LDP-IGF without active enediyne was also cytotoxic to A549 cells at high concentrations (50 and 100 μg·mL-1). LDP-IGF-AE could cause significant G2-M arrest in A549 and H460 cells, and it also induced the apoptosis in NSCLC cells in a concentration-dependent manner. CONCLUSION: Fusion protein LDP-IGF-AE shows potent antitumor efficacy in vitro on NSCLC, suggesting it could be a promising candidate for targeted therapy.

The purpose of this paper is to optimize the course construction and teaching process of psychopharmacology， and analyze the problems in the course of teaching and assessment of psychopharmacology from many aspects. This article is to deeply excavate the space for improvement， and enrich the teaching links by using existing conditions， technology and personnel to enhance the teaching effect and improve the teaching quality， so as to provide references for the reform of similar course teaching.

【Objective】To explore miRNA-138 protecting cardiomyocyte apoptosis of neonatal rats by inhibiting JNK/ p38 MAPK pathway.【Methods】Thirty-three whole blood samples from patients with acute myocardial ischemia during the period from January 2018 to December 2018 were collected. Thirty- three whole blood samples from healthy people who underwent physical examination in the same period were enrolled as controls. Ischemia/reperfusion（I/R）models of neonatal rats were established. Forty neonatal rats were randomly divided into blank control group（Control），model group（I/R model），negative control group（injected with unordered sequence）and miRNA-138 overexpression group（Ad-miRNA-138），with 10 cases in each group. The expression of miRNA- 138，Bcl2 and Bax mRNA in whole blood and myocardial tissues was detected by qRT-PCR. The levels of rat hemodynamic indexes were detected by electrophysiological recorder. The pathological damages of myocardial tissues were observed by HE staining. The expression of Caspase- 3 in myocardial tissues was detected by immunohistochemistry. The apoptosis of myocardial cells was observed by TUNEL staining. The content of reactive oxygen species （ROS） in myocardial tissues was detected by ELISA. The expression of JNK/p38 MAPK pathway protein was detected by Western blotting. 【Results】 Compared with healthy control，the level of whole blood miRNA- 138 was significantly decreased in patients with acute myocardial ischemia（P<0.05）. Compared with I/R model group，cardiomyocyte gap in Ad-miRNA-138 group was smaller，its arrangement was more uniform，and its structure was more complete. The miRNA- 138 expression，levels of cardiac function indexes such as +dp/dtmax，HR，LVSP and Bcl2/Bax were significantly increased，while number of apoptosis cells，rate of Caspase-3 positive-expression cells， ROS，p-p38/p38，Pc-jun/c-jun and p-JNK1/2/JNK1/2 were significantly down-regulated（P<0.05）.【Conclusion】MiRNA- 138 can inhibit cardiomyocyte apoptosis of rats，and reduce ROS damage by inhibiting JNK/p38 MAPK pathway， thus protecting cardiomyocytes of neonatal rats.

BackgroundAnxiety exists as a prevalent psychological problem among college students nowadays， which brings negative influence on their normal life. Mobile phone addiction and loneliness both have an impact on college students' anxiety. However， the acting path of loneliness between mobile phone addiction and anxiety requires further exploration. ObjectiveTo analyze the relationships among mobile phone addiction， loneliness and anxiety in college students， and to explore the acting path of loneliness between mobile phone addiction and anxiety. MethodsOn December 21， 2023， 1 400 college students from a university in Henan Province were selected， in accordance with the simple random sampling method， for investigation of this study. Questionnaire survey was conducted by using several scales including Mobile Phone Addiction Tendency Scale （MPATS）， Self-rating Anxiety Scale （SAS） and University of California Los Angeles-Loneliness Scale （UCLA-LS）. Pearson correlation analysis was used to examine the correlation between the scores of each scale above， and SPSS macro program Process 3.3 was used to test the mediation effect. ResultsA total of 1 239 valid questionnaires were collected， with an effective recovery rate of 88.50%. The MPATS score of college students was positively correlated with both SAS and UCLA-LS scores （r=0.474， 0.387， P<0.01）， and UCLA-LS score was positively correlated with SAS score （r=0.541， P<0.01）. The indirect effect of loneliness between mobile phone addiction and anxiety was 0.160 （95% CI： 0.118~0.173）， accounting for 33.97% of the total effect. ConclusionMobile phone addiction can positively predict anxiety among college students， and loneliness may act as the mediation path between mobile phone addiction and anxiety among college students.

Sesquiterpenoid is a kind of compound widely distributed in nature, which has a wide range of biological activities, such as anti-inflammatory, anti-tumor and immunomodulatory activities. This paper would review the anti-inflammatory mechanism of sesquiterpenoid. The mechanism is mainly by inhibiting the activation of nuclear factor (NF-κB), mitogen-activated protein kinase (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways and down-regulating the inflammatory gene expression including tumor necrosis factor- (TNF-), prostaglandin E₂ (PGE₂), nitric oxide (NO), interleukin-1(IL-1), IL-6, IL-8 and other inflammatory factors. Thereby, the production and release of inflammatory cytokines are reduced to exert anti-inflammatory effect. This review is intended to provide reference for related research.
Anti-Inflammatory Agents ; pharmacology ; Dinoprostone ; Humans ; Interleukins ; MAP Kinase Signaling System ; NF-kappa B ; Nitric Oxide ; STAT Transcription Factors ; Sesquiterpenes ; pharmacology ; Signal Transduction ; Tumor Necrosis Factor-alpha

BackgroundDepression is a kind of disease with relatively high suicide risk， which seriously affects the quality of life of patients and their families， and brings a great burden to society. Antidepressants in western medicine are effective， but the improvement of depressive symptoms is relatively limited by single use， and the combination of two antidepressants may increase the risk of adverse reactions in patients. The rational use of Chinese patent medicine and western medicine may play a complementary role， and the safety of Chinese patent medicine is high. ObjectiveTo explore the early clinical efficacy of fluoxetine combined with Shugan Jieyu capsule in the treatment of depression， and to compare the differences in efficacy， safety and influence on heart rate variability between fluoxetine combined with Shugan Jieyu capsule and fluoxetine alone， so as to provide references for clinical medication of depression patients. MethodsFrom December 2015 to June 2016， 64 patients who met the diagnostic criteria of depression in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） who were hospitalized in the Second Affiliated Hospital of Xinxiang Medical University were selected as the research objects， and were randomly divided into the combined medication group and the fluoxetine group with 32 patients in each group. Patients in both groups were treated with fluoxetine， while patients in the combined medication group were treated with Shugan Jieyu capsule on this basis. Patients in both groups were assessed with Hamilton Depression Scale-24 item （HAMD-24）， Hamilton Anxiety Scale （HAMA） and Heart Rate Variability （HRV） before treatment， and were assessed with HAMD-24 and Treatment Emergent Symptom Scale （TESS） at the end of the 2^nd， 4^th and 6^th week of treatment， and HRV was analyzed again at the end of the 6^th week of treatment. ResultsThe study ultimately included 60 patients with depression， with 30 cases in the combination therapy group and 30 cases in the fluoxetine group. At the end of the 2^nd， 4^th and 6^th week of treatment， the HAMD-24 score of the combined drug group was lower than that of the fluoxetine group （t=-2.677， -3.960， -4.432， P<0.05 or 0.01）. Compared with before treatment， the 24-hour mean standard deviation of normal RR intervals （SDNN）， normal low frequency （nLF） and normal high frequency （nHF） in the combined treatment group were higher at the end of the 6^th week （t=-73.970， -31.878， -38.721， P<0.01）， but significant lower in LF/HF （t=3.525， P<0.01）. At the end of the 6^th week of treatment， the total effective rate of the combined treatment group was higher than that of fluoxetine group， and the difference was statistically significant （86.67% vs. 70.00%， χ²=18.764， P<0.01）. At the 2^nd， 4^th and 6^th week of treatment， there was no significant difference in the number of adverse reactions between the two groups （P>0.05）. ConclusionCompared with fluoxetine alone， Shugan Jieyu capsule combined with fluoxetine may be better in clinical efficacy and improvement of heart rate variability in patients with depression， without increasing adverse reactions.

ObjectiveTo develop a rehabilitation program of nature posture treatment (NPT) suspension therapy based on the International Classification of Functioning, Disability and Health-Children and Youth version (ICF-CY) framework, and apply it to neurodevelopmental disorders. MethodsThe ICF-CY theoretical group (group A) and NPT suspension therapy group (group B) were established. Group A searched literature from common databases, to extract high-frequency words related to suspension therapy and match with categories of ICF-CY, to develop ICF-CY theoretical framework of the NPT suspension therapy. Group B developed specific rehabilitation procedures and training items based on the framework to compose the training pool. A total of 110 children aged less than six years with neurodevelopmental disorders and associated motor impairments were selected from outpatient or inpatient of the First Affiliated Hospital of Xinxiang Medical University, between October, 2019 and October, 2022. They were randomly divided into control group (n = 55) and clinical group (n = 55), who received routine neurodevelopmental therapy and NPT suspension therapy program based on ICF-CY, respectively, for a week. The incidence of satisfaction, acceptance and adverse events were observed. ResultsTwo cases in the control group and four cases in the clinical group dropped down. For the clinical group, the incidence of satisfaction was 98% (50/51), with acceptance of 96% (49/51), and one adverse event occurred. For the control group, the incidence of both the satisfaction and acceptance was 100%, and no adverse event occurred. There was no significant difference in the incidence of satisfaction, acceptance and the adverse event (P > 0.05). ConclusionThe NPT suspension therapy program based on the ICF-CY framework is safe and acceptable for children with neurodevelopmental disorders.

OBJECTIVETo investigate the effects of mannan-binding lectin (MBL) on the maturation and cytokine secretion of human dendritic cells (DC) induced by Candida albicans (C. albicans).

METHODSThe plastic-adherent mononuclear cells were prepared from the blood of healthy adult volunteers. The human peripheral blood mononuclear cells-derived dendritic cells (MNC-DC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2 days in presence or absence of C. albicans at varying concentration of human MBL ranging from 1 to 20 mg/L. DC's shape and characters were observed under inverted microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The levels of TNF-α and IL-6 were detected by ELISA. FACS also was used to investigate the interaction of MBL with immature DC(imDC) and C. albicans. Western blot was used to detect C. albicans-induced IκBα phosphorylation and p65/NF-κB translocation in DC.

RESULTSMBL at higher concentrations (10-20 mg/L) down-regulated the expression of CD83 and CD86 on the monocyte-derived dentritic cells(MoDC) induced by C. albicans, and inhibited the production of TNF-α and IL-6 induced by C. albicans. FACS showed that MBL could not only bind to C. albicans but also bind to imDCs in a Ca2+-dependent manner. Western blot showed that MBL could decrease the phosphorylation of IκBα and the nuclear translocation of p65/ NF-κB.

CONCLUSIONMBL may inhibit TNF-α and IL-6 production induced by C. albicans in DC through NF-κB signaling pathways, suggesting that MBL can play some roles in the regulation of C. albicans-induced immune response.

OBJECTIVE To explore the effects of esmolol on cardiac function， inflammatory factors and serum microRNA （miR）-29a and miR-129-5p in patients with acute anterior ST-segment elevation myocardial infarction after percutaneous coronary intervention （PCI）. METHODS A total of 120 patients with acute anterior ST-segment elevation myocardial infarction undergoing PCI in our hospital from April 2021 to June 2023 were selected and divided into control group （60 cases） and study group （60 cases） according to the random number table method. The control group was given conventional treatment， and the study group was additionally given Esmolol hydrochloride injection based on the control group for one week. The levels of cardiac function indexes （left ventricular ejection fraction， left ventricular end-systolic volume index， left ventricular end-diastolic diameter， peak ejection fraction， cardiac output）， inflammatory factors （C-reactive protein， myeloperoxidase， interleukin-6， brain natriuretic peptide， homocysteine） myocardial enzyme indexes （creatine kinase isoenzyme， β2-microglobulin， cardiac troponin Ⅰ）， and serum expression of miR-29a and miR-129-5p were observed in two groups， and the occurrence of ADR was recorded. RESULTS After one week of treatment， left ventricular ejection fraction， peak ejection fraction， cardiac output， and the expression of miR-129-5p in two groups was significantly higher than before treatment （P＜0.05）， while left ventricular end-systolic volume index， left ventricular end-diastolic diameter， inflammatory factors and myocardial enzyme index levels， and the expression of miR-29a were significantly lower than before treatment （P＜ 0.05）. The study group was significantly better than the control group （except for the creatine kinase-MB） （P＜0.05）. There was no statistically significant difference in the incidence of symptomatic hypotension， symptomatic bradycardia， cardiogenic shock， and arrhythmia between two groups （P＞0.05）. CONCLUSIONS Esmolol can improve cardiac function， reduce inflammatory factors， lessen myocardial injury， and regulate serum expressions of miR-29a and miR-129-5p in patients with acute anterior ST- segment elevation myocardial infarction after PCI， with good safety.