Objective To analyze the efficacy and safety of trastuzumab (H) and pertuzumab (P) combined with different chemotherapy regiments in neoadjuvant therapy for HER2-positive breast cancer. Methods We retrospectively analyzed the clinical data of the patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy and completed surgery. The primary endpoint was total pathologic complete response (tpCR) (ypT0/isypN0), the secondary endpoints were breast pathologic complete response(bpCR) (ypT0/is) and axillary pathologic complete response (apCR) (ypN0), and the factors influencing pCR were analyzed. Results A total of 63 patients were included, of whom 23 were treated with TCbHP, 27 were treated with THP regimen, and 13 were treated with AC-THP. The overall tpCR rate was 65.1%, of which TCbHP was 73.9%, THP was 55.6%, and AC-THP was 69.2%. The tpCR rate of HR-negative patients was 79.2%, higher than that of HR-positive 56.4%. The overall bpCR rate was 69.8%, and apCR rate was 81.0%. Univariate analysis showed that HER2 status was a related factor affecting tpCR (P=0.023). The total effective rate by MRI was 87.3%. The level 3 and 4 toxicity of the TCbHP regimen was slightly higher than those of the THP and the AC-THP regimens. Conclusion HP combined with chemotherapy have achieved relatively high pCR. HER2 status is a related factor that affects tpCR. The adverse reactions are controllable.

Objective To investigate the effects of Dermatophagoides pteronyssinus ( Der p) on the expression of TLR4 and IL-4 in P815 mast cells and to further analyze the immunoregulatory effects of 1,25-(OH)2D3 on Der p treated P815 mast cells.Methods Different concentrations of Der p and 1,25-( OH) 2 D3 were used alone or in combination to stimulate P815 mast cells.The supernatants of the stimulated cell culture were analyzed by enzyme-linked immunosorbent assay ( ELISA) for the detection of IL-4.The stimulated cells were collected and analyzed by real-time PCR and Western blot assays for the detection of TLR4atmRNAandproteinlevels,respectively.Results (1)TLR4expressionwasdetectedinP815 cells.The expression of TLR4 was enhanced in P815 cells treated with various concentrations of Der p.A significant dose-dependent up-regulation of TLR4 was observed in P815 cells after incubation with Der p for 36 h.(2) Der p promoted the release of IL-4 in P815 cells (P<0.05).(3) No significant differences with the expression of TLR4 and IL-4 were observed among 1,25(OH)2D3 treatment groups as compared with the control group (P>0.05).(4) 10-8 mol/L of 1,25(OH)2D3 promoted the Der p-induced expression of TLR4 in P815 cells (P<0.01).However, 1,25(OH)2D3 inhibited the release of IL-4 in a dose-dependent manner(P<0.05orP<0.01).Conclusion (1)Derpcouldpromotetheinflammationandallergicreac-tion through up-regulating TLR4 and IL-4 in mast cells.(2) The possible mechanism for the inhibitory of 1, 25(OH)2D3 on Der p-induced immune responses was due to the suppression of Th2-type immune responses through inhibiting the synthesis and secretion of IL-4 in mast cells.

Objective: To investigate the effect of thalidomide on the expressions of Th17 cells, interleukin 17 (IL-17), macrophage inflammatory protein 3α (MIP3α) in peripheral blood of patients with diffuse large B-cell (DLBCL) and 3-year survival rate. Methods: Sixty patients with DLBCL from January 2009 to January 2013 in the Affiliated Hospital of Hebei University of Engineering were enrolled. According to envelope method, the patients were randomly divided into the combined group (n = 30, thalidomide combined with CHOP regimen) and chemotherapy group (n = 30, CHOP regimen alone). Clinical adverse reactions, efficacy, the expressions of Th17 cells, IL-17, MIP3α in peripheral blood before and after treatment, and 3-year survival rate between two groups were compared. Results: The total effective rate and 3-year survival rate were 73.3% (22/30) vs. 46.7% (14/30), 87.4% vs. 40.7% respectively in the combined group and the chemotherapy group (both P < 0.05). The levels of Th17 cells percentage and the expression level of IL-17 before and after treatment in combined group were (0.52±0.14)% vs. (1.61±0.53)%, (5.61±0.75) pg/ml vs. (8.87±1.84) pg/ml, and the difference was statistically significant (both P < 0.05). However, the expression levels of Th17 cells and IL-17 before and after treatment in the chemotherapy group were (0.75±0.05)% vs. (0.74±0.07)%, (5.69±0.29) pg/ml vs. (5.26±0.24) pg/ml, and there was no statistical difference (both P > 0.05). The levels of IL-17 and MIP3α mRNA in peripheral serum before and after treatment in the combined group were 8.51±0.23 vs.13.96±0.89, 27.4±1.5 vs. 83.0±8.5 (both P < 0.05). While in the treatment group before and after treatment the above mentioned were 8.85±0.32 vs. 9.45±0.55, 23.7±1.8 vs. 38.7±5.5, and the difference was no statistically significant (both P > 0.05). There was no statistical difference in the adverse reactions between the combined group and the chemotherapy group (P > 0.05). Conclusion Thalidomide may prolong survival time of DLBCL patients by intervening Th17 cells and associated cytokines.

Objective Vascular endothelial growth factor C (VEGFC) and cortactin (CTTN) have been found to be closely related to the growth of esophageal squamous cell carcinoma (ESCC), but their specific relationship has not been clearly defined up to the present time. This study aimed to investigate the effects of VEGFC and CTTN on the proliferation and apoptosis of ESCC cells. Methods Human ESCC TE1 cells were treated with normal culture medium (the blank control group), MATE transfection reagent ( the MATE group), negative control RNA and MATE reagent (the negative control group), positive control RNA and MATE reagent (the positive control group), VEGFC siRNA and MATE transfection reagent (the VEGFC siRNA group), and CTTN siRNA and MATE transfection reagent (the CTTN siRNA group). The proliferation of the ESCC TE1 cells in different groups was detected by CCK-8 assay and their apoptosis determined by flow cytometry. Results Compared with the blank control group, the ESCC cells of the VEGFC siRNA and CTTN siRNA groups showed significantly decreased expressions of VEGFC mRNA (1.00 ± 0.00 vs 0.13 ± 0.01, P < 0.05) and CTTN mRNA (1.00 ± 0.00 vs 0.29 ± 0.02, P < 0.05). The proliferation rate of the ESCC cells was remarkably lower in the VEGFC siRNA and CTTN siRNA than in the other groups (P < 0.05), and even lower in the VEGFC siRNA than in the CTTN siRNA group ([31.26 ± 5.25]% vs [46.99 ± 4.82]%, P < 0.05), but their apoptosis rate was markedly higher in the former than in the latter group ([48.41 ± 5.37]% vs [36.78 ± 4.29]%, P < 0.05). Conclusion Interfering with the expressions of VEGFC and CTTN can inhibit the proliferation and promote the apoptosis of ESCC cells, and VEGFC has an even better effect than CTTN.

Objective To investigate the effect of micro-ribonucleic acid-21(miR-21) on the malignant biological behavior of human cholangiocarcinoma cell line QBC939 by targeting the protein tyrosine phosphatase (PTEN)/inositol phosphate 3-kinase (PI3K)/protein kinase B (Akt) pathway. Methods The cholangiocarcinoma cell line QBC939 in the logarithmic growth phase was divided into empty vector group, blank control group, overexpression group, and silencing group.An inverted fluorescence microscope was used to observe transfection efficiency; MTT assay, flow cytometry, Transwell assay, and wound healing assay were used to measure cell proliferative activity, apoptosis rate, invasion activity, and migration activity.Quantitative reverse transcription PCR was used to measure the mRNA expression levels of miR-21, PTEN, PI3K, Akt, and mammalian target of rapamycin (mTOR); Western blotting was used to measure the protein expression levels of PTEN, PI3K, Akt, phosphorylated Akt (p-Akt), and mTOR; dual-luciferase reporter assay was used to verify the effect of miR-21 on PTEN.A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK- q test was used for further comparison between two groups. Results Transfection efficiency was 90.27%±18.03% in the overexpression group, 91.43%±18.26% in the silencing group, and 92.16%±18.41% in the empty vector group.Compared with the blank control group and the empty vector group, the overexpression group had a significant increase in the proliferative activity of QBC939 cells (both P < 0.05) and a significant reduction in apoptosis rate (both P < 0.01);compared with the blank control group, the empty vector group, and the overexpression group, the silencing group had a significant reduction in proliferative activity ( P < 0.01) and a significant increase in apoptosis rate ( P < 0.01).Compared with the blank control group and the empty vector group, the overexpression group had significant increases in the migration rate of QBC939 cells and number of cells penetrating the membrane (all P < 0.01);compared with the blank control group, the empty vector group, and the overexpression group, the silencing group had significant reductions in migration rate and number of cells penetrating the membrane (all P < 0.01).Compared with the blank control group and the empty vector group, the overexpression group had significant increases in the mRNA expression levels of miR-21, PI3K, Akt, and mTOR and a significant reduction in the mRNA expression level of PTEN (all P < 0.05);compared with the blank control group, the empty vector group, and the overexpression group, the silencing group had significant reductions in the mRNA expression levels of miR-21, PI3K, Akt, and mTOR and a significant increase in the mRNA expression level of PTEN (all P < 0.05).Compared with the blank control group and the empty vector group, the overexpression group had significant increases in the protein expression levels of PI3K, Akt, p-Akt, and mTOR and a significant reduction in the protein expression level of PTEN (all P < 0.01);compared with the blank control group, the empty vector group, and the overexpression group, the silencing group had significant reductions in the protein expression levels of PI3K, Akt, p-Akt, and mTOR and a significant increase in the protein expression level of PTEN (all P < 0.01).Furthermore, miR-21 showed targeted regulation of PTEN expression. Conclusion MiR-21 silencing may inhibit the malignant biological behavior of human cholangiocarcinoma cell line QBC939 by targeting the PTEN/PI3K/Akt signaling pathway to upregulate the expression of PTEN and downregulate the expression of PI3K, Akt, mTOR, and p-Akt.

OBJECTIVETo observe the efficacy of acupoint catgut embedding therapy combined medication on chronic urticaria induced by Helicobacter pylori (HP) infection.

METHODSNinety-two cases were randomly divided into 3 groups, named a medication group (group A, 31 cases), an acupoint catgut embedding group (group B, 30 cases) and a medication combined acupoint catgut embedding group (group C, 31 cases). In group A, the medication was administered orally for antihistamine and anti-HP infection. In group B, catgut embedding was applied on Quchi (LI 11), Xuehai (SP 10), Zusanli (ST 36), etc. In group C, acupoint catgut embedding therapy was applied in combination with medication (medication as group A, acupoint catgut embedding as group B). After 3-month treatment, the efficacy, recurrence rate and HP negative rate were compared among 3 groups.

RESULTSSeparately, the effective rates of group A, B, C were 61.3% (19/31), 53.3% (16/30) and 90.3% (28/31); the recurrence rates were 27.3% (3/11), 33.3% (3/9) and 5.9% (1/17); and HP negative rates were 31.3% (10/31), 26.7% (9/30) and 77.4% (24/31). The clinical efficacy and HP negative rate in group C were superior to those in group A and B (P < 0.01, P < 0.05).

CONCLUSIONAcupoint catgut embedding therapy combined medication is significant in efficacy and low in recurrence rate in treatment of chronic urticaria caused by HP infection.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Catgut ; Chronic Disease ; therapy ; Combined Modality Therapy ; Female ; Helicobacter Infections ; drug therapy ; microbiology ; therapy ; Helicobacter pylori ; physiology ; Histamine Antagonists ; therapeutic use ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Urticaria ; drug therapy ; microbiology ; therapy ; Young Adult

Objective:To investigate the relationship between the mechanism of mental dependence of propofol and adenosine A2A receptor-neurotransmitter-extracellular signal-regulated kinase (ERK) pathway in rats.Methods:Forty-eight healthy male Sprague-Dawley rats, aged about 7 weeks, weighing 200-300 g, were used in this study.The model of propofol dependence was established by intraperitoneal injection of propofol 40 mg/kg for 14 consecutive days.The rats were divided into 6 groups ( n=8 each) using a random number table method: central control group (group c-C), central agonist group (group c-CGS), central antagonist group (group c-DMPX), peripheral control group (group p-C), peripheral agonist group (group p-CGS) and peripheral antagonist group (group p-DMPX). Adenosine A2A agonist CGS-21680 2.5 ng/0.5 μl was intracranially injected immediately after establishing the model in group c-CGS, while the equal volume of normal saline was given instead in c-C group.CGS-21680 0.1 mg/kg was intraperitoneally injected in group p-CGS, while the equal volume of normal saline was given instead in group p-C.Adenosine A2A receptor antagonist DMPX 50 ng/0.5 μl was intracranially injected at 20 min before each propofol injection in group c-DMPX, and DMPX 0.25 mg/kg was intraperitoneally injected in group p-DMPX.The position preference value (CPP value) was determined before establishing the model, immediately after establishing the model, and after administration of agonist or normal saline (after intervention). The animals were sacrificed at 1 day after establishing the model, and blood samples and brain tissues were obtained for determination of the levels of dopamine (DA) and glutamate (Glu) in plasma and hippocampus and content of serotonin (5-HT) in cerebral cortex (by enzyme-linked immunosorbent assay) and expression of phosphorylated ERK1/2 (p-ERK1/2) in cerebral cortex (by Western blot). Results:Compared with the baseline before establishing the model, CPP value was increased immediately after establishing the model in c-C, c-CGS, p-C and p-CGS groups ( P<0.05), and no significant change was found in CPP value immediately after establishing the model in c-DMPX and p-DMPX groups ( P>0.05). Compared with the value immediately after establishing the model, no significant change was found in CPP value after intervention in c-C and p-C groups ( P>0.05), and CPP value was increased after intervention in c-CGS and p-CGS groups ( P<0.05). Compared with group c-C, the contents of hippocampal DA and Glu were significantly increased in group c-CGS, and the contents of hippocampal Glu were decreased, the content of 5-HT in cerebral cortex was increased, and the expression of p-ERK1/2 was down-regulated in group c-DMPX ( P<0.05). Compared with group p-C, no significant change was found in levels of DA and glutamate (Glu) in plasma and hippocampus and 5-HT and p-ERK1/2 in cerebral cortex in group p-CGS ( P>0.05), and the contents of hippocampal DA and Glu were significantly decreased, the content of 5-HT in cerebral cortex was increased, and the expression of p-ERK1/2 was down-regulated in group p-DMPX ( P<0.05). Conclusion:The mechanism underlying the development of propofol mental dependence may be related to activating adenosine A2A receptors, increasing excitatory neurotransmitters in brain, and thus up-regulating ERK activity in rats.

Objective: To investigate the effect of diabetes on the risk of stroke recurrence within 1 year after onset of ischemic stroke. Methods: Patients with ischemic stroke admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from October 2016 to August 2017 were enrolled prospectively. Their baseline clinical data were collected and they were followed up for one year. The risk factors for ischemic stroke in recurrence group and non-recurrence group were compared. Cox proportional hazard regression model was used to determine the independent risk factors for ischemic stroke recurrence. Kaplan-Meier survival analysis was used to explore the impact of risk factors on the risk of stroke recurrence. Results: A total of 1 436 patients with ischemic stroke were included. During the follow-up of 1 year, a total of 183 patients had recurrence (12.74%). There were significant differences in the proportion of patients with diabetes, atrial fibrillation, hyperhomocysteinemia, oral antiplatelet drugs, and statins after discharge, and baseline fasting blood glucose level between the recurrence and the non-recurrence group (all P<0.05). Multivariate Cox proportional hazards analysis showed that diabetes mellitus (hazard ratio [HR] 1.574, 95% confidence interval [CI] 1.161-2.134; P=0.003) was an independent risk factor for stroke recurrence. Taking statins (HR 0.686, 95% CI 0.481-0.979; P=0.038) and antiplatelet agents (HR 0.678, 95% CI 0.467-0.983; P=0.041) after discharge were the independent protective factors for ischemic stroke recurrence. Kaplan-Meier survival analysis showed that the recurrence rate of ischemic stroke in patients with diabetes was significantly higher than that in those without diabetes (log-rank test, P=0.003). The recurrence rate of stroke in patients taking statins and antiplatelet drugs was significantly lower than that in patients who did not take the corresponding drugs (log-rank test, all P<0.001). Conclusions Diabetes is an independent risk factor for ischemic stroke recurrence, and taking statins and antiplatelet drugs are the independent protective factors for ischemic stroke recurrence.

OBJECTIVE: To study the role of Nrf2/ARE signaling pathway in cypermethrin-induced oxidative stress and apoptosis of cerebral cortex neurons in C57BL/6 mice. METHODS: The cortical neurons of C57BL/6 mice were cultured and identified, and a cypermethrin-induced cell injury model was established by treating the cells with 0, 25, 50 and 100 μmol/L of cypermethrin for 48 h. CCK-8 assay was used to analyze the effects of cypermethrin on the cell viability, and the fluorescence probe DCFH-DA was used for detecting intracellular reactive oxygen species (ROS); flow cytometry was performed for determining the apoptosis rate of the cells. The mRNA and protein expression levels of Nrf2 and its downstream genes HO-1 and NQO1 were detected using qPCR and Western blotting. RESULTS: Exposure to cypermethrin at different doses inhibited the viability of the cultured cortical neurons. With the increase of cypermethrin dose, the viability of the neurons decreased progressively, the intracellular ROS and the cell apoptosis rate increased, and the neuronal injury worsened. At the dose of 50 and 100 μmol/L, cypermethrin significantly down-regulated the expressions of HO-1, NQO1 and Nrf2 at both the mRNA and protein levels in the cells ( < 0.01). CONCLUSIONS Cypermethrin exposure shows a dose-dependent neurotoxicity by inhibiting Nrf2/ARE signaling pathway, down-regulating the expression of Nrf2 and its downstream genes HO-1, NQO1 mRNA and protein, and inducing oxidative damage and apoptosis in primary mouse cortical neurons, .
Animals ; Carboxylic Ester Hydrolases ; Cerebral Cortex ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2 ; Neurons ; Pyrethrins ; Signal Transduction

【Objective】 To analyze the basic characteristics of whole blood donors from blood stations before and after the outbreak of COVID-19. 【Methods】 After excluding invalid data, data related to the basic characteristics of whole blood donors collected from 26 blood stations in China during 2018 to 2021 were statistically analyzed, including the trend of total whole blood donors, the number of repeated blood donors, the frequency of blood donation, the average age of donors and the recruitment of first-time blood donors. 【Results】 Affected by the epidemic, 8 out of 14 indicators were with large variations, accounting for 57%. The overall growth rate of total whole blood donors during the epidemic was higher than before the epidemic (P<0.05).The number of repeated blood donors has shown an increased trend, with a higher number during the epidemic than before (P<0.05). The frequency of blood donation was lower during the epidemic than before(P<0.05).Average ages of blood donors and female blood donors fluctuated widely during the epidemic, both higher than those before the epidemic(P<0.05).The donation rate of first-time blood donors <25 years old and ≥25 years old varied widely and irregularly during the epidemic (both P<0.05). The percentage of first-time blood donors fluctuated irregularly during the epidemic, with overall percentage lower than that before the epidemic(P<0.05). 【Conclusion】 Whole blood donors from 26 blood stations increased after the outbreak of COVID-19, and some indicators in certain areas showed significant fluctuations during the epidemic.