Objective To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α) and construction of collateral circulation in patients with coronary artery disease. Methods Collateral vessels were determined in 96 patients with≥70% narrowing of at least one coronary artery without prior revascularization,42 patients with coronary artery collaterals and 54 patients with no coronary artery collaterals.Another 50 cases with normal coronary arteries were selected as control.The levels of HIF-lα expression in monocytes and lymphocytes were tested by immunohistochemistry (IHC) and Western blot.Results Compared to the controls,the patients had higher expression of HIF-1α(P<0.01).Higher HIF-1α expression was found in patients with collaterals than in those without collaterals (P<0.01).Positive correlation was observed between the expression of HIF-1α protein and collateral score (r1=0.78,r2=0.84,P<0.01).Conclusion HIF-1α expression in circulating monocytes and lymphocytes are associated with collateral circulation.Detection HIF-1α might be helpful in the prognosis of patients with coronary artery disease.

Objective To investigate the structural response of diaphragm and soleus of the rat after mechanical ventilation (MV), and to explore the specific mechanism of the dysfunction of both muscles.Methods Sixteen male Sprague-Dawley (SD) rats were randomly divided into control group and MV group, with 8 rats in each group. Rats in MV group were treated with controlled ventilation and maintained anesthesia, and those in control group were only anesthetized without MV and maintained anesthesia. The diaphragm and soleus were harvested after MV for 18 hours, and the morphology changes were observed with light microscope. The cross section of muscle fiber was observed by immunofluorescence technique analysis, and the cross-sectional area of muscle fiber was calculated. The ultra structural changes in muscle fibers were observed under transmission electron microscope.Results ① Observed under light microscope, the cross section of the diaphragm and soleus muscle in the control group was regular, the nucleus was normal and the cytoplasm was homogeneous. The fibers in the diaphragm-biopsy specimens from MV subjects were smaller than those from control subjects, whereas these signs were not found in soleus. But fiber atrophy in MV specimens was not accompanied by an inflammatory-cell infiltrate. ② Under the fluorescence microscope, the control group had a smaller cross-section of the slow-twitch muscle in diaphragm, while the fast-twitch muscle fibers werelarger. As compared with diaphragm-biopsy specimens from control, specimens from MV subjects showed decreased cross-sectional areas of slow-twitch and fast-twitch fibers, respectively (μm2: 1069.00±155.24 vs. 1297.12±331.15, 2279.66±442.31 vs. 3031.80±596.11, bothP < 0.05). The disproportionate decrease in fast-twitch fibers cross-sectional areas [(70.42±3.61)% vs. (75.63±2.48)%] resulted inan increase in the percentage of total area occupied by the slow-twitch fibers [(29.58±3.61)% vs. (24.35±2.48)%, bothP < 0.01]. There were no significant differences in cross-sectional areas of slow-twitch and fast-twitch fibers in soleus between control group and MV group (μm2: 3193.80±559.36 vs. 3008.84±559.22, 3392.86±514.56 vs. 3594.35±651.67, bothP > 0.05). ③ In the control group, the muscle fibers of the diaphragm and soleus were arranged orderly, the boundary of the light and dark bands and the Z-line were clear, and there was no autophagy in the visual field. The outer membrane of the mitochondria was complete, and the cristae were in the shape of clapboard. The signs of misalignment of myofibrils, disruption of Z-line and vacuolar mitochondria were found in diaphragm from MV group, whereas these signs were not found in soleus. Diaphragm from MV group exhibited an increase in autophagic vesicles visualized by transmission electron microscopy as compared with control group.Conclusions Controlled MV for 18 hours resulted in diaphragmatic inactivity and promoted muscle injury and atrophy, while autophagy and mitochondrial dysfunction were enhanced. Soleus immobilization for 18 hours was not associated with muscle atrophy. These facts suggest that the signaling associated with diaphragm atrophy during MV may involve different mechanisms compared with other models of muscle atrophy. Diaphragm appeared to be more susceptible to MV.

OBJECTIVE To observe the effect of the silver sulfadiazine-impregnated hydrocolloid dressing on the pain of nail extraction wound during dressing change and the healing time of wound. METHODS Forty eight patients with nail extraction were randomly divided into two groups: in the study group,whose wound was covered with silver sulfadiazine-impregnated hydrocolloid dressing;in the control group,whose wound was applied vaseline gauze when the nail had been extracted and the wound was applied antibiotic gauze during dressing change.The pain scores of two groups were compared.Two groups were compared with healing time and the times of dressing change. RESULTS The pain scores in the study group were significantly lower than that of the control group.The healing time of wound and the times of dressing change in the study group were less than that of the control one((P

OBJECTIVETo use a hospital-based case-control study design to investigate the relationship between hepatocellular carcinoma (HCC) and the interaction of polymorphisms in the human mismatch repair gene,hMSH2,with environmental factors.

METHODSCases of new-onset,histopathology-diagnosed,and untreated (no chemotherapy or radiation therapy) HCC were enrolled between September 2009 and September 2012.A non-HCC healthy control group was also enrolled and was composed of individuals living in the same region as the cases for more than 10 years and age-/sex-matched with similar socioeconomic characteristics.All enrollees underwent hMSH2 genotyping by real-time PCR.T-test,chi-square test and unconditional logistic regression analysis was used to analyze the difference in allele frequencies among the case and control groups and the relationship between hMSH2 polymorphisms and environmental factors.

RESULTSFrequencies of hMSH2 rs2303428 CC,CT and TT genotypes in the HCC group were significantly different than in the control group (14.13% vs.8.21%,47.02% vs.49.47%,and 38.85% vs.42.32%;x 2=8.289,P =0.016).Individuals carrying the hMSH2 rs2303428 T allelic gene had a significantly increased risk compared to those with the hMSH2 rs2303428 C allelic gene (adjusted OR=1.228).Interactions were found between the hMSH2 genotype and hepatitis B surface antigen (HBsAg)-positive hepatitis infection (adjusted OR=1.865) and history of cancer (adjusted OR=5.634).There was no relation between hMSH2 gene rs4952887 and rs2059520 and liver cancer development or interaction with environmental factors.

CONCLUSIONThe hMSH2 rs2303428 genotype is positively related to risk of HCC in Chinese,with HBsAg-positive hepatitis infection starus and history of cancer increasing the risk.

Alleles ; Carcinoma, Hepatocellular ; genetics ; Case-Control Studies ; Female ; Gene Frequency ; Genotype ; Humans ; Liver Neoplasms ; genetics ; Male ; MutS Homolog 2 Protein ; genetics ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction

ObjectiveTo investigate the molecular mechanism of the anti-liver fibrosis effect of curcumol by observing the effect of curcumol on the TLR4/NF-κB signaling pathway in liver sinusoidal endothelial cells. MethodsA total of 50 mice were randomly divided into blank group, model group, and curcumol group, and cells were divided into blank control group, LPS positive control group, curcumol intervention group, and PDTC group. HE staining and Masson staining were used to observe the change in liver structure; Western blot and quantitative real-time PCR (RT-PCR) were used to measure the protein and mRNA expression of the key molecules TLR4 and NF-κB in the TLR4/NF-κB signaling pathway; immunofluorescence assay was used to observe the expression and nuclear import of NF-κB in cells. A one-way analysis of variance was used for comparison between multiple 　groups, and the least　significant difference t-test was used for further comparison between two groups.　ResultsRT-PCR showed that compared with the positive control group, the curcumol intervention group had significant reductions in the mRNA expression of TLR4 and NF-κB (both P＜0.05). Western blot showed that compared with the positive control group, the curcumol intervention group had significant reductions in the expression of TLR4 and NF-κB (both P＜005). Immunofluorescence assay showed that compared with the positive control group, the curcumol intervention group had significant improvement in NF-κB nuclear import. ConclusionCurcumol can exert an anti-liver fibrosis effect possibly by inhibiting the activity of the TLR4/NF-κB signaling pathway.

Objective To investigate the effect of final vowel types on the voice onset time(VOT)of differ-ent stops in children with hearing impairment,and to provide a basis for the acquisition and correction of stop sounds.Methods A total of 22 hearing-impaired children aged 3～6 and 22 children with normal hearing were ran-domly selected-18 consonant-vowel(CV)syllables composed of 6 stops and 3 single finals were recorded,using first tone.Using Praat 6.1.29 software to analyze and extract the stops VOT.Two-way ANOVA was used for each stop,the dependent variable was VOT,and the independent variables were hearing status and final type.Results Children in the hearing-impaired group had articulation errors in/t/,/g/,and/k/.Hearing status had significant effect on the main effect of plosives/g/,/p/,/t/,/k/(P＜0.05),and the VOT of slurs/g/,/p/,/t/,/k/in the normal hearing group significantly greater than the hearing-impaired group(P＜0.05).The main effect of finals on the VOT of the stops/b/,/p/and/t/was significant(P＜0.05).Hearing status and final type had an interac-tive effect on the stop/t/,and the simple main effect showed that the difference in VOT of/ti/between the hear-ing-impaired group and the normal hearing group was greater than that of/ta/and/tu/.Conclusion The stops/g/,/p//t/,/k/VOT of hearing-impaired children are smaller than those of with normal hearing.The difference in VOT of/ti/sound between the hearing impaired group and the normal hearing group is greater than that of/ta/sound and/tu/sound.In the teaching of the initial/t/sound for hearing-impaired children,we can start with/ta/and/tu/with less difference,and the/ti/sound is consolidated later.Pay attention to breathing and oral exercise training,to lay a good foundation for clear pronunciation.

Objective:To investigate the promotion effect of 4,5,6,7-tetrabromobenzotriazole (TBB)on the apoptosis of human colon cancer SW480 cells,and to explore its possible mechanism.Methods:The human colon cancer SW480 cells at logarithmic growth phase were divided into control group (0 μmol·L-1 TBB)and experiment group (1,3,10,30,and 100 μmol·L-1 TBB).The viability of cells was measured by MTT assay;the apoptotic rate of the SW480 cells and the level of intracellular reactive oxygen species (ROS)were analyzed by Annexin Ⅴ-FITC/PI double staining and flow cytometry.The expression levels of anti-apoptotic proteins p-Akt and Bcl-2,and pro-apoptotic proteins Bad, pro-caspase-9 and cleaved-caspase-3 were detected by Western blotting method. Results:The MTT results showed that the viabilities of SW480 cells in experiment group were decreased in a dose-dependent manner,which were lower than that in control group (P < 0.05).The Annexin Ⅴ-FITC/PI double staining and flow cytometry results showed that the apoptotic rates of SW480 cells in experiment group (3,6,12, and 24 h)were significantly higher than that in control group (0 h)(P <0.05).The flow cytometry results showed the levels of ROS in SW480 cells after treated with TBB for 3,6,12 and 24 h were higher than that in 0 h group (P <0.05).The Western blotting results showed that the expression levels of anti-apoptotic proteins p-Akt and Bcl-2 in SW480 cells in experiment group (3,6,12,and 24 h)were decreased obviously,whereas the expression levels of the pro-apoptotic proteins Bad and cleaved-caspase-3 were increased and the expression level of pro-caspase-9 was decreased compared with those in control group (0 h) (P < 0.05 ).Conclusion: TBB could inhibit the cell proliferation and induce the apoptosis of human colon cancer SW480 cells,and its mechanism may be related to the inhibition of the activity of Akt and the promotion of the level of intracellular ROS.

Objective:To explore the value of high-resolution CT (HRCT) visual scores and quantitative analysis in assessing pulmonary Langerhans cell histiocytosis (PLCH) in adults.Methods:In total 51 adult patients with PLCH confirmed by pathology in Peking Union Medical College Hospital from August 2014 to December 2021 were retrospectively analyzed. All patients underwent HRCT and pulmonary function tests (PFT). The involvement of the nodular and cystic lesions were evaluated by two experienced radiologists using CT visual scores. The cases were divided into three groups based on the nodular scores, and into four groups based on the cystic scores, respectively. Ratio of low attenuation areas (LAA%) was measured by an automatic post-processing software. Pulmonary function indices including forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), FEV 1/FVC, diffusion capacity for carbon monoxide of lung (D LCO), alveolar ventilation (V A), D LCO/V A, D LCO corrected for hemoglobin (D LCOc), D LCOc/V A were collected. FEV 1/FVC was expressed as measured values and other indices were expressed as percent predicted (%pred). Spearman correlation analysis was used to evaluate the correlation between HRCT visual scores, LAA% and PFT. The lung function indices among different nodular groups as well as among different cystic groups were compared using the Kruskal‐Wallis test. Results:Both nodular and cystic lesions were found on HRCT images of all 51 patients. There were no correlation between the visual scores of nodular lesions and lung function indices (all P>0.05). There were no significant differences in lung function indices among different nodular groups (all P>0.05). The visual scores of cystic lesions were negatively correlated with FEV 1/FVC, D LCO%pred, D LCO/V A%pred, D LCOc%pred, D LCOc/V A%pred ( r=-0.491, -0.347, -0.330, -0.373, -0.346, respectively, all P<0.05); the pulmonary function indices among different cystic groups had significant difference (all P<0.05). LAA% were negatively correlated with FEV 1/FVC, D LCO%pred, D LCO/V A%pred, D LCOc%pred, D LCOc/V A%pred ( r=-0.278, -0.378, -0.418, -0.395, -0.451, respectively, all P<0.05). Conclusion:HRCT visual scores of nodular lesions do not correlate with lung function in patients with PLCH. Visual scores and quantitative analysis of the cystic lesions can reflect the impairment degree of pulmonary ventilation and diffusion function to a certain extent, and may be used in assessment of patients with PLCH.

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1