Objective To observe the effect of exposure of emphysema with intermittent hypoxia on oxidative stress injury of myocardial cells in rats. Methods Sixty male Wistar rats were divided randomly into four experimental groups(each n=15). The normal control group was bred normally. The emphysema group was exposed to cigarette smoke twice a day(once 30 minutes). The intermittent hypoxia(IH)group was exposed to intermittent hypoxia circumstance 8 hours/day,and the emphysema with IH group was exposed to cigarette smoke twice a day (once 30 minutes)and intermittent hypoxia circumstance 8 hours/day. Each group was exposed for 8 weeks. At the beginning of 9 weeks,the blood gas analysis was performed in 5 rats selected randomly from each group,and the rest rats were sacrificed and their hearts and lungs were taken. Under light microscope,the lung tissues stained with hematoxylin-eosin(HE)were examined. The lung pathology and the results of blood gas analysis showed that the emphysema with IH rat model was established successfully. The levels of malonaldehyde(MDA)and superoxide dismutase(SOD)in rat myocardium were measured by enzyme-linked immunosorbent assay(ELISA),and the subunit p22phox mRNA expressions of nicotinamide adenine dinucleotide phosphate(NADPH)-oxidase were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR). Results Compared with the normal group, the MDA levels and p22phox mRNA expressions were increased obviously in emphysema group, IH group and emphysema with IH group〔MDA(μmol/g):2.93±0.54, 3.58±0.63, 4.51±0.72 vs. 1.75±0.56, p22phox mRNA:0.043±0.004,0.067±0.015,0.123±0.016 vs. 0.018±0.002,all P<0.05〕,but the activities of SOD were decreased significantly(U/mg:36.07±4.79,33.51±7.12,24.29±5.36 vs. 46.08±5.12,all P<0.05). In emphysema with IH group,the increase of MDA levels and p22phox mRNA expressions and decrease of SOD levels were more remarkable compared with those in emphysema group and IH group(all P<0.05). The expression of p22phox mRNA was positively correlated with MDA level(r=0.734,P<0.001). Conclusion The myocardial tissue oxidative stress injury in rats induced by emphysema with intermittent hypoxia exposure is more serious than that induced by exposure of either emphysema or intermittent hypoxia alone,NADPH oxidase possibly being the important medium of myocardial cell response to oxidative stress.

Objective To investigate the effect of intermittent hypoxia (IH) with pulmonary emphysema on the ex-pression of hypoxia inducible factor-1α(HIF-1α),Bax and Bcl-2, and the mechanism underlying the role of HIF-1αin he-patocyte apoptosis thereof. Methods Sixty rats were randomly divided into four groups: normal control group, rats were treated normally;IH group, rats were treated by 30 s nitrogen and then 90 s air, and rats were treated by from 9:00-17:00 daily;pulmonary emphysema group, rats were treated by smudging for half an hour, twice a day (8:00 and 18:00);IH with pul-monary emphysema group, rats were treated by 30 s nitrogen and then 90 s air from 9:00-17:00 daily. After exposure four-teen weeks, rats were killed. qRT-PCR assay was conducted to detect the expression of HIF-1α mRNA, Bax mRNA and Bcl-2 mRNA in live tissues. Results The expressions of HIF-1αmRNA, Bax mRNA and Bax/Bcl-2 were significantly higher in IH with pulmonary emphysema group than those in control group,IH group and pulmonary emphysema group (P<0.05). The expression level of Bcl-2 mRNA was significantly lower in IH with pulmonary emphysema group than that of con-trol group and pulmonary emphysema group (P < 0.05), but no significant difference compared with that of IH group (P >0.05). The levels of HIF-1αand Bax were positively correlated with the level of Bax/Bcl-2 (r=0.732 and 0.699),but the lev-els of HIF-1αand Bax were negatively correlated with the level of Bcl-2 (r=-0.705). Conclusion The expression levels of HIF-1αmRNA, Bax mRNA and Bcl-2 mRNA were over-regulated in hepatocytes induced by intermittent hypoxia with pul-monary emphysema. The HIF-1αexpression was correlated with Bax and Bcl-2, suggesting that HIF-1αmay promote the hepatocyte apoptosis through transcriptional co-activators, Bax and Bcl-2.

Objective To explore the mechanism of Lkb1 regulated epithelial regeneration in asthma by airway organoid culture.Methods Lkb1f/f(the control group,n=10)and Scgb1a1CreER;Lkb1f/fmice(the Lkb1 knockout group,n=9)were taken to establish allergic asthma models by aerosol inhalation of ovalbumin(OVA).Bronchial lavage fluid(BALF)and lung tissue were collected.The number of inflammatory cells in BALF were counted.The amount of CLCA3 positive cells was compared by immunofluorescence staining of lung tissue sections.Club cells were selected by flow cytometry for organoid culture.The average diameter of organoids and organoid formation rate were calculated.Expression levels of goblet cell marker CLCA3,cilia cell markers FOXJ1 and AMPK in Club cells were detected by RT-PCR.Results There were no significant differences in the number of macrophages,eosinophils,neutrophils and lymphocytes in BALF between the control group and the Lkb1 knockout group.The number of CLCA3 positive cells were decreased after Lkb1 knockout.Results of organoid culture showed that the average diameter of organoids derived from Club cells and organoid formation rate were decreased after the absence of Lkb1.The expression of FOXJ1 was reduced.After Lkb1 deletion,the expression of AMPKα in Club cells were decreased and the proliferation of Club cells was inhibited.Activation of AMPK,the downstream signaling pathway of Lkb1,could attenuate the effect of Lkb1 deficiency on the regeneration of Club cells.Conclusion Lkb1 promotes the proliferation of airway progenitor cells by AMPK pathway.

OBJECTIVETo investigate the antineoplastic effects of 2-Deoxy-D-glucose (2-DG) combined with Taxol on orthotopically transplanted breast cancer in C3H mice and explore the mechanism.

METHODSC3H mice bearing orthotopically transplanted breast cancer xenograft were randomly divided into 4 groups, namely the control group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs were administered intraperitoneally every 3 days for 18 consecutive days, and the tumor volume was measured every 3 days to draw the tumor growth curve. The mice were then sacrificed to measure the tumor weight on day 19 and examine tumor cell apoptosis with TUNEL assay and VEGF expression using immunohistochemistry.

RESULTS2-DG combined with Taxol obviously suppressed the tumor growth with a tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group. The combined treatment also caused more obvious cell apoptosis and significantly reduced VEGF expression in the tumor cells as compared with the other groups.

CONCLUSION2-DG can enhance the inhibitory effect of Taxol on orthotopically transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell apoptosis and lowering VEGF expressions.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Apoptosis ; Breast Neoplasms ; drug therapy ; pathology ; Cell Line, Tumor ; Deoxyglucose ; pharmacology ; therapeutic use ; Drug Synergism ; Female ; Mice ; Mice, Inbred C3H ; Paclitaxel ; pharmacology ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism ; Xenograft Model Antitumor Assays

Objective To investigate the antineoplastic effects of 2- Deoxy- D- glucose (2- DG) combined with Taxol on orthotopically transplanted breast cancer in C3H mice and explore the mechanism. Methods C3H mice bearing orthotopically transplanted breast cancer xenograft were randomly divided into 4 groups, namely the control group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs were administered intraperitoneally every 3 days for 18 consecutive days, and the tumor volume was measured every 3 days to draw the tumor growth curve. The mice were then sacrificed to measure the tumor weight on day 19 and examine tumor cell apoptosis with TUNEL assay and VEGF expression using immunohistochemistry. Results 2-DG combined with Taxol obviously suppressed the tumor growth with a tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group. The combined treatment also caused more obvious cell apoptosis and significantly reduced VEGF expression in the tumor cells as compared with the other groups. Conclusion 2-DG can enhance the inhibitory effect of Taxol on orthotopically transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell apoptosis and lowering VEGF expressions.

With the deepening of China's medical reform, people's demand for health is growing, which promotes the construction of "new medicine" and puts forward higher requirements for the cultivation and education of medical students. Undergraduate medical education is a crucial period for the growth of medical students, and how to do a good job in undergraduate teaching under the background of "new medicine" is currently a research hotspot. The clinical teaching stage is an important period for medical students to fully understand clinical disciplines and cultivate their understanding of specialties. Therefore, we should explore new teaching methods and means to adapt to the needs of the new era. In the context of "new medicine", the medical-engineering fusion diagnosis and treatment technology has become an important trend in the clinical diagnosis and treatment of oncology. In order to adapt to this change, clinical teaching and teaching management in oncology also need new exploration and research. Taking the clinical teaching of oncology as an example, this article discusses how to cultivate medical students' thinking of medical-engineering fusion.

Objective To investigate the antineoplastic effects of 2- Deoxy- D- glucose (2- DG) combined with Taxol on orthotopically transplanted breast cancer in C3H mice and explore the mechanism. Methods C3H mice bearing orthotopically transplanted breast cancer xenograft were randomly divided into 4 groups, namely the control group, 2-DG group, Taxol group, and 2-DG+Taxol group. The corresponding drugs were administered intraperitoneally every 3 days for 18 consecutive days, and the tumor volume was measured every 3 days to draw the tumor growth curve. The mice were then sacrificed to measure the tumor weight on day 19 and examine tumor cell apoptosis with TUNEL assay and VEGF expression using immunohistochemistry. Results 2-DG combined with Taxol obviously suppressed the tumor growth with a tumor inhibition rate of 66.06% as compared to the rate of 36.97% in Taxol group. The combined treatment also caused more obvious cell apoptosis and significantly reduced VEGF expression in the tumor cells as compared with the other groups. Conclusion 2-DG can enhance the inhibitory effect of Taxol on orthotopically transplanted breast cancer xenograft in C3H mice probably by inducing tumor cell apoptosis and lowering VEGF expressions.

Objective:To clarify the relationship between interleukin (IL)-6, IL-10 gene polymorphisms and autoimmune thyroid disease (AITD).Methods:Literature search was conducted through databases such as PubMed, Web of Science, CNKI, Embase, Wanfang Database and VIP.com, and domestic and foreign literatures related to IL-6, IL-10 gene polymorphisms and AITD were included in the study. The time limit was from the self-built of the databases to July 2021. Meta-analysis was performed with STATA 16.0 software, the odds ratio ( OR) and 95% confidence interval ( CI) were used as effect indicators, random-effect or fixed-effect model was selected according to the heterogeneity results, and the source of heterogeneity was explored through subgroup analysis. Publication bias was assessed using funnel plots and Egger's test. Results:Finally, 19 literatures were included, all in English. There were 12 studies on IL-6 genes and 11 studies on IL-10 genes, including 4 studies on both IL-6 and IL-10 genes. In the whole population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR =1.94, 95% CI = 1.01 - 3.76), IL-6 -572 G/C site (GG + GC vs CC: OR = 0.49, 95% CI = 0.29 - 0.84; GG vs CC + GC: OR = 0.76, 95% CI = 0.60 - 0.96; GG + CC vs GC: OR = 0.63, 95% CI = 0.49 - 0.81), IL-10 -819 T/C site (TT + TC vs CC: OR = 1.84, 95% CI = 1.01 - 3.34; T vs C: OR = 1.59, 95% CI = 1.00 - 2.51), and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.77, 95% CI = 0.64 - 0.92; AA vs GG + AG: OR = 2.03, 95% CI = 1.16 - 3.58; A vs G: OR = 0.76, 95% CI = 0.61 - 0.94). The results of subgroup analysis showed that in Asian population, the loci associated with AITD were IL-6 -174 G/C site (GG vs CC + GC: OR = 4.61, 95% CI = 1.11 - 19.23; G vs C: OR = 0.65, 95% CI = 0.44 - 0.97); IL-6 -572 G/C site (GG vs CC + GC: OR = 0.64, 95% CI = 0.41 - 0.99; GG + CC vs GC: OR = 0.60, 95% CI = 0.38 - 0.94); IL-10 -819 T/C site (TT + TC vs CC: OR = 2.51, 95% CI = 1.48 - 4.25; T vs C: OR = 1.91, 95% CI = 1.05 - 3.46); and IL-10 -1 082 A/G site (AA + AG vs GG: OR = 0.66, 95% CI = 0.52 - 0.84; AA vs GG + AG: OR = 2.83, 95% CI = 1.54 - 5.21; A vs G: OR = 0.66, 95% CI = 0.53 - 0.82). Conclusion:IL-6 -174 G/C, IL-6 -572 G/C, IL-10 -819 T/C and IL-10 -1 082 A/G polymorphisms are associated with the susceptibility to AITD, especially in Asians.

Objective This study aimed to identify differentially methylated genes (DMGs) associated with natural killer cells in patients with autoimmune thyroiditis (AIT),focusing on the influence of varying water iodine exposure levels. Methods Participants were divided into categories based on median water iodine (MWI) concentrations:iodine-fortified areas (IFA,MWI<10 μg/L),iodine-adequate areas (IAA,40 ≤ MWI ≤ 100μg/L),and iodine-excessive areas (IEA,MWI>300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89,40,and 47 pairs for IFA,IAA,and IEA,respectively. DMGs were identified using 850K BeadChip analysis for 10/10 paired samples. Validation of DNA methylation and mRNA expression levels of the DMGs was conducted using MethylTarget? and QRT-PCR for 176/176 paired samples. Results KLRC1,KLRC3,and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed,whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore,KLRC1 was hypomethylated and highly expressed in both IFA and IEA. Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally,DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.