Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract that includes Crohn's disease and ulcerative colitis.IBD may be caused by complex interactions between genetic susceptibility,environmental factors,and alterations in the gut microbiota,resulting in dysregulated innate and adaptive immune responses.Recent studies have identified macrophages in the intestinal inflammatory response as having the plasticity to not only regulate inflammation,but also to promote tissue repair and healing.As aberrant macrophage polarization occurs during the development of IBD,the balance between the phenotype and function of pro-inflammatory M1 and anti-inflammatory M2 macrophages is regulated by extracellular and intracellular stimuli,and this process is therefore expected to be a potential target for new therapeutic approaches.This article reviewed the progress of research on macrophage polarization in IBD.

Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.

Based on the theory of “manifestation-body and spirit-qi”， it is considered that the pathogenesis of tic disorders （TD） involves three manifestations of “wind， phlegm and fire”， with wind as the leading factor and phlegm and fire as the accompanying factors. It is advocated to identify the abnormality of body and spirit， summarize the evolution of manifestation， and prescribe flexibly based on qi movement of zang-fu organs. Among them， the common symptoms related to tics are mostly belong to wind symptoms， which originated from lung qi failing to purify and liver qi over-ascent. The method of soothing liver wood and purifying lung gold is adopted， and modified Xiaochaihu Decoction （小柴胡汤） and Cangerzi Powder （苍耳子散） are recommended； Patients with prolonged illness and strange symptoms are often mixed with phlegm， which stemmed from the fact that spleen failing to rise clear and stomach failing to downward turbid. The method of raising spleen-earth and lowering stomach-earth is adopted， and modified Yigong Powder （异功散） and Erchen Decoction （二陈汤） are recommended； Patients with severe symptoms are often mixed with fire symptoms， which originated from discordance of water and fire and hyperactivity of heart fire. The method of interacting heart and kidney and coordinating water and fire is adopted， and modified Xiegan Pill （泻肝丸） and Liuwei Dihuang Pill （六味地黄丸） are recommended， in order to regulate qi movement， harmonize body and spirit， and improve the symptoms.

Objective:To investigate the current situation of satisfaction with graduate education among recent medical graduates in China, and analyze the differences between different populations, and to propose countermeasures and suggestions.Methods:From June to July 2023, a self-made questionnaire was used to survey 16 903 medical graduates who had recently earned a post-graduate degree from 78 institutions about their satisfaction with curriculum sessions, practical sessions, research training, tutoring, and institutional management. The degrees of satisfaction with education among different populations were compared through the t test and analysis of variance with the use of SPSS 26.0. Results:The scores of satisfaction of the graduates with tutoring, curriculum sessions, practical sessions, institutional management, and research training were 4.44, 4.03, 4.02, 3.90, and 3.82, respectively. Satisfaction scores for individual dimensions were significantly higher for males, doctors, non-transfers, comprehensive universities, non-agricultural household registration, moderate-to-high annual household income per capita, parents with high educational levels, and parents with mid- or senior-level occupations ( P<0.05). Conclusions:There is room for improvement in students' satisfaction with medical graduate education. To improve the quality of medical graduate education, attention should be paid to key populations, education policies, school management, and tutoring to provide appropriate education for different students.

Objective To explore the preventive effect of dexamethasone hydrochloride injection at Zusanli acupoint on nausea and vomiting after gynecological laparoscopic surgery under general anesthesia.Methods Between January 2021 and March 2022,78 patients scheduled for gynecological laparoscopic surgery were randomly divided into study group and control group with 39 cases in each group.Ondansetron(4 mg)was intravenously injected in both groups before surgery,and dexamethasone(5 mg)was injected additionally at Zusanli acupoint in the study group.The perioperative heart rate(HR),mean arterial pressure(MAP),blood oxygen saturation(SpO2)and operation time of the two groups were recorded.The levels of motilin and vasoactive intestinal peptide and the incidences of nausea,vomiting and routine adverse reactions were compared between the two groups.Results There was no significant difference in HR,MAP,SpO2 or operation time between the two groups before and 48 h after operation(P>0.05).The incidences of nausea and vomiting in the study group were lower than those in the control group 24 h after operation.Postoperative motilin and vasoactive intestinal peptide levels in the study group were lower than those in the control group(P<0.05).Postoperative motilin and vasoactive intestinal peptide levels in the control group were higher than those before operation(P<0.05).There was no significant difference in the total incidences of routine adverse reactions such as fatigue or headache between the two groups(P>0.05).Conclusion Dexamethasone hydrochloride injection at Zusanli acupoint is helpful to stabilize the motilin and vasoactive intestinal peptide levels and significantly reduce the incidences of postoperative nausea and vomiting.

Objective:To investigate whether irradiated U251 glioma cells can induce bystander effects in unexposed neural stem cells (NSCs) thus affecting its proliferation, stemness and differentiation.Methods:The cells were divided into NSCs group, NSCs+ U251 group (co-cultured with U251) and NSCs+ IR U251 group (co-cultured with 10 Gy irradiated U251). Glioma cells and NSCs were co-cultured in a transwell insert set. Cell counting and neurosphere diameter measuring were carried out to evaluate the proliferation and neurosphere formation ability of NSCs. Immunofluorescence assay was performed to detect the expression of Nestin protein to evaluate the stemness maintenance of NSCs, and to measure the expression levels of Tuj1 and GFAP proteins, the number of neuronal dendrites, synaptic length, the number of glial protrusions, as well as the length of glial protrusions.Results:The number of NSCs cultured with irradiated U251 cells was obviously smaller than that of NSCs cultured with sham-irradiated U251 cells ( t=2.52, P<0.05). The neurosphere formation ability of NSCs and the percentage of Nestin positive NSCs after co-culture with irradiated U251 cells significantly reduced in comparison with those after co-culture with sham-irradiated U251 cells ( t=-3.50, P<0.05). The percentages and the extent of NSCs differentiating into neuronal cells and glial cells( t=6.09, P<0.05)decreased obviously after co-culture with irradiated U251 cells in comparison with those after co-culture with sham-irradiated U251 cells. Conclusions:Irradiated glioma cells can significantly inhibit the proliferation, stemness and differentiation of unexposed NSCs due to bystander effect.

Objective:To systematically review the effects of the traditional Chinese medicine compound based on astragalus and angelica on bone marrow suppression after chemotherapy.Methods:Randomized controlled trials (RCTs) about the traditional Chinese medicine compound based on astragalus and angelica for bone marrow suppression after chemotherapy for malignant tumors were retrieved from Cochrane Library, PubMed, Web of Science, CINAHL, OVID, SinoMed, CNKI, VIP, and Wanfang Databases. The search period was from the establishment of the database to September 2019. The literatures were screened and the data were extracted independently by two researchers and RevMan 5.3 was used for Meta-analysis.Results:Totally 15 RCTs were included, involving 1 019 patients. Meta-analysis results showed that there were statistically significant differences in peripheral blood leukocytes [ SMD=1.32; 95% CI (0.76, 1.89) ; P<0.000 01], platelets [ MD=25.05; 95% CI (8.00, 42.10) ; P=0.004], hemoglobin [ MD=24.14; 95% CI (16.34, 31.94) ; P<0.000 01] and clinical symptoms [ RR=1.38; 95% CI (1.25, 1.52) ; P<0.000 01] between the chemotherapy group, the chemotherapy combined with the western medicine group and the traditional Chinese medicine compound group. Conclusions:The traditional Chinese medicine compound based on astragalus and angelica can improve the level of peripheral blood cells, reduce bone marrow suppression, and improve clinical symptoms and quality of life of patients with cancer after chemotherapy. However, due to the low quality of the included literature and the large heterogeneity of some of the results, more rigorously designed high-quality RCTs are needed for further verification.

Objective To investigate the effect of PDCA cycle management combing with ECG guidance in improving the rate of catheter tip in right place when is conducting the PICC catheterization. Methods A total of 36 intravenous treatment specialist nurses from Jiangsu Tumor Hospital were trained with PDCA cycle management method from 1st June to 31st September,2016. The training knowledge and skills included catheter tip positioning under intracardiac electrocardiogram. The knowledge and skills were analyzed and compared before and after training finally. Results The training not only could help to improve the score of knowledge and skill of PICC specialist nurses with knowledge before (88.28±3.10) and after (96.10±1.25) (P< 0.05) and skill before (83.55±5.11) and after (98.81±2.50) (P< 0.05); but also increased the rate of catheter tip in right place in the process of PICC catheterization (χ2=12.35,P <0.05). Meanwhile, the results showed that patient satisfaction with nurses could also be improved from 88.7% to 96.8% (χ2=10.79,P <0.05) and the operating time could be shorted [before (40.23±3.56)min,after (28.76±4.34)min](P< 0.05). Conclusions The use of PDCA circulatory method to train nurses can improve the ability to deal with puzzling questions of nurses in the process of PICC catheterization,and increase the rate of PICC catheter tip in right place.

Objective The pathogenesis of intractable epilepsy was explored by examining the expression of the P-gp , GST-Pi as well as MDR1 in peripheral blood of the patients with intractable epilepsy. The potential of the above mentioned three genes as the biomarkers for treatment of intractable epilepsy was investigated. Methods Thirty-one sub?jects with refractory epilepsy, 33 subjects under good circumstances by antiepileptic drugs, and 37 healthy subjects were included in the present study. fluorescence quantitative polymerase chain reaction and flow cytometry were used to detect mRNA levels of MDR1 and GST-Pi and P-gp of MDR1 in the peripheral blood of the patients, respectively. Results The expression levels of MDR1 and GST-Pi were significantly higher in the AEDs intractable group(1.36±0.14,0.585±0.257) than in the treatment group(0.82±0.15,0.309±0.217, P<0.05)The expression levels of MDR1 and GST-Pi were signifi?cantly higher in the AEDs treatment group than in the normal group(0.27±0.07,0.134±0.223,P<0.05). The expression levels of P-gp were significantly higher in the AEDs of the intractable group(0.104±0.084)than in the treatment group (0.063 ± 0.030, P<0.05). The GST-Pi gene expression levels were significantly higher in three(0.535 ± 0.256)or two (0.425±0.254)kinds of antiepileptic drugs combination therapy than in single drug treatment(0.267±0.265, P<0.05). Leucocyte P-gp levels were significantly higher in combination therapy of three kinds of antiepileptic drugs(0.141 ± 0.096)than in combination therapy of two kinds of antiepileptic drugs(0.071±0.020)or in monotherapy(0.050±0.020, P<0.05). Conclusion MDR1 and GST-Pi gene expression levels of peripheral blood can be used as the reference in?dex for treatment of intractable epilepsy and the resistant index of combination treatment for intractable epilepsy.