Objective To study the hematopoietic stem cell injury(HSC)induced by busulfan. Methods C57BL/6 mice were treated with i.p. injection of 20 mg/kg or 40 mg/kg busulfan. All mice were euthanized at 15 days and 30 days after busulfan treatment for analysis of the peripheral blood cell counts, bone marrow cellularity and HPC (LKS-, lineage-sca1 -c-kit+), HSC(LSK, lineage-sca1 +c-kit+)and long-term HSC(CD34 - LSK, CD34 - lineage-sca1 +c-kit+)frequency. The colony-forming unit-granulocyte and macrophage(CFU-GM)ability of HPC was measured by colony-forming cell(CFC)assay,and the HSC self-renewal capacity was analyzed by single-cell colony-forming assay. Results The busulfan administration decreased the WBC,RBC and PLT compared with control mice. The HPC function (CFU-GM)was impaired(P < 0.05), and the HSC colony forming ability was decreased at 15 days after busulfan treatment(P < 0.05), whereas the body weight of the mice didn't change significantly after busulfan treatment. Conclusions Our findings suggest that busulfan can induce hematopoietic stem cell injury,and provide a support for the study of hematopoietic stem cell injury mechanism.

Objective To explore the analysis of the relationship of the serum levels of focal adhe-sion kinase(FAK)and fatty acid-binding protein 4(FABP4)with myocardial injury and cardiac function in elderly patients with acute myocardial infarction(AMI).Methods A total of 211 AMI patients admitted to our hospital from January 2020 to April 2023 were enrolled and assigned into the AMI group,while another 60 healthy volunteers who took routine physical examinations in our hospital during the same period served as the control group.The serum FAK and FABP4 lev-els were compared between the two groups.Multivariate logistic regression analysis was employed to identify influencing factors associated with AMI,and ROC curve was plotted to assess the pre-dictive efficacy of the serum FAK and FABP4 levels for AMI in the elderly population.Pearson correlation analysis was conducted to explore the relationship between serum FAK and FABP4 levels and myocardial injury as well as cardiac function.Results The AMI group exhibited signifi-cantly elevated serum FAK,FABP4,CK-MB,cTnⅠ and CK levels,and larger LVESD and LVEDD,but lower LVEF when compared with the control group(P＜0.05,P＜0.01).For the AMI patients,the serum FAK and FABP4 levels were positively correlated with CK-MB,cTnⅠ and CK levels,as well as LVESD and LVEDD,and negatively with LVEF(P＜0.05).Multivariate logistic regression analysis revealed that both serum levels of FAK(OR=2.872,95％CI:2.230-3.698,P=0.000)and FABP4(OR=2.667,95％CI:1.713-4.154,P=0.000)were influencing factors for AMI.ROC analysis indicated that the cut-off value of FAK level for diagnosing AMI was 25.60 pg/L,with an AUC value of 0.801(95％CI:0.750-0.852).Similarly,the cut-off value of FABP4 in the diagnosis was 23.22 pg/L,with an AUC value of 0.760(95％CI:0.707-0.812).Combined FAK and FABP4 levels yielded,with an AUC value of 0.899(95％CI:0.839-0.918).Conclusion Serum FAK and FABP4 levels are abnormally high in the elderly patients with AMI,which is closely related to myocardial injury and cardiac function.The two indicators alone or in combination can effectively predict the occurrence of AMI.

Objective:To investigate high resolution CT (HRCT) manifestations and clinical features of patients infected with the novel coronavirus B.1.617.2 variant.Methods:A total of 125 patients with the novel coronavirus B.1.617.2 variant in Guangzhou Eighth People′s Hospital from May 21 to June 9, 2021 was enrolled. There were 52 males and 73 females, aged from 1 to 92 years old with a median age of 47 year. The clinical features and HRCT characteristics were analyzed retrospectively.Results:Of the 125 patients, the main clinical manifestations were fever in 54 patients, cough in 50 patients, pharyngeal discomfort in 39 patients, and diarrhea in 5 patients. HRCT showed pneumonia in 96 cases, which predominantly had ground-glass opacities in 92 cases, ground-glass opacities combined with local consolidation in 22 cases, consolidation in 11 cases, intralobular interstitial thickening in 51 cases, centrilobular structural thickening in 23 cases, and cord-like lesions in 33 cases. One patient had pleural effusion, and no enlarged lymph nodes were observed in all patients. The lesions were distributed in the subpleural and/or peripheral lung in 96 cases and along the bronchovascular bundle (middle and inner zone) in 24 cases. The time interval from onset to positive HRCT was 3 (1, 4) days in 96 patients with pneumonia on HRCT. HRCT showed absorption after the imaging findings reaching the peak in 20 patients, and the time interval between the first positive HRCT findings and the peak imaging was 6 (3, 7) days in these 20 patients.Conclusions:The novel coronavirus B.1.617.2 variant has a strong infectivity, short viral latency. Lung injury is decreaseel. People of all ages are susceptible and the diseasemay have rapid pnegression. HRCT mainly shows ground glass opacities, which are more common in subpleural and/or in the lung periphery, with interlobular thickening.

Objective: To investigate the initial HRCT manifestations and clinical features of imported novel coronavirus pneumonia (NCP) in Guangzhou. Methods: A retrospective analysis of 91 NCP patients admitted to the Guangzhou Eighth People’s Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years, then their clinical features and HRCT characteristics were analyzed. Results: The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry coughin39 cases). The first time HRCT showed that 24 cases with NCP were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung. Conclusions The initial images of NCP in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of NCP patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.

Objective:To investigate whether endoplasmic reticulum aminopeptidase 1 ( ERAP1) is a susceptible gene for pre-eclampsia (PE) and the possible mechanism in the pathogenesis. Methods:This retrospective study included 990 PE patients (case group) and 1 240 healthy pregnant women (control group) in six prefecture-level tertiary hospitals in Shandong Province, including the Affiliated Hospital of Qingdao University and Zaozhuang Maternal and Child Health Hospital, from September 2018 to April 2021. Peripheral blood were collected for DNA extraction. Single-nucleotide polymorphisms in the ERAP1 gene (rs30187, rs27044, and rs469783 loci) were analyzed by Taqman probe polymerase chain reaction (PCR). Two missense mutant plasmids, rs30187(c.1583A>G) and rs27044(c.2188C>G), were constructed by point mutation induction based on wild-type plasmids. Six groups (knock-down control, knock-down, over-expression control, over-expression, variant 1 and 2 groups) were set up in this study. After transfecting Htr8 cells with different transfection molecules, the expression of ERAP1 at mRNA and protein levels were detected. Besides, the effects of different transfections on cell function were detected using Transwell migration assay, Transwell invasion assay, cell scratch assay, and CCK-8 assay. Statistical analysis was performed using two independent samples t-test, rank sum test, and Chi-square test. Results:(1) There were significant differences in the genetic distribution of rs30187 (Genotype: χ2=29.25, Allele: χ2=4.68) and rs469783 (Genotype: χ2=7.01, Allele: χ2=6.45) as well as the genotype distribution of rs27044 ( χ2=28.95) between the case group and the control group (all P<0.05). Statistical analysis of the genetic model revealed that rs30187 and rs27044, both recessive models, were statistically different between the two groups with a higher frequency of CC genotypes in the case group ( χ2=20.82 and 19.97, both P<0.05), but a lower frequency in CC dominant gene pattern for rs469783 ( χ2=5.82, P=0.016). (2) Compared with the knock-down control group, the knock-down group showed significantly inhibited expression of ERAP1 (mRNA: 0.5±0.1 vs 1.0±0.0, t=7.49; protein: 0.4±0.1 vs 0.7±0.1, t=2.81; both P<0.05), reduced cell migration rate after 48 h of scratching [(16.5%±1.8%) vs (23.8%±2.4%), t=3.33, P=0.031] and decreased number of cells crossing Transwell chambers after 24 h of culture (423.7±21.3 vs 499.0±24.6, t=3.29, P=0.031). Compared with the over-expression group, variant 1 group and variant 2 group showed significantly inhibited expression of ERAP1 at mRNA (both P<0.001) and protein ( P=0.003 and 0.006) levels after transfection, decreased number of cells crossing Transwell chambers ( P=0.001 and 0.032) and down-regulated cell migration rate after 48 h of scratching [variant 1: P=0.004; variant 2: (21.1±4.6)% vs (28.3±1.1)%, t=2.10, P=0.099]. ERAP1 expression at both mRNA ( P<0.001) and protein ( P=0.008) levels, as well as cell proliferation ( P<0.001) and invasion ability ( P<0.001), were all enhanced in the over-expression group than those in the over-expression control group. Moreover, the migration rate of cells after 48 h of scratching ( P=0.002) and the number of cells crossing Transwell chambers after 24 h of culture ( P=0.001) were also increased. Conclusions:The rs30187, rs27044, and rs46978 on ERAP1 gene were all associated with PE susceptibility, with more carriers of the CC genotype in PE patients at rs30187 and rs27044 loci and more carriers of the CC genotype in healthy gravida at rs469783 locus. ERAP1 may be involved in the pathogenesis of PE by affecting the migratory and invasive ability of trophoblast cells.

Oral submucous fibrosis (OSF) can cause various oral dysfunctions in patients and can turn into oral cancer. The causes and processes of OSF malignant transformation involve betel nut chewing, vascular atrophy, tissue hypoxia, cell cycle changes, aging, autophagy, and changes in cancer/cancer suppressor genes and microRNAs. It is of great significance to study the causes and process of OSF malignant transformation for the treatment and prevention of OSF malignant transformation.

Forkhead box protein O1 (FOXO1) has been extensively studied as a tumor suppressor. In oral squamous cell carcinoma, studies have demonstrated that FOXO1 can inhibit tumor cell oxidative stress, stemness and epithelial-mesenchymal transition, and promote tumor cell autophagy and apoptosis. FOXO1 may serve as a potential target for the treatment of oral squamous cell carcinoma.

BACKGROUND:The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways,augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells,osteocytes,osteoclasts,and osteoblasts,thus facilitating the process of periodontal remodeling. OBJECTIVE:To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS:The PubMed,Web of Science,China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy.And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION:Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause,leading to autophagy in periodontal tissue.Subsequently,autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B,Hippo,and mitogen-activated protein kinase pathways,promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability.Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side.Related targets have good prospects in the clinical application of orthodontic treatment.Orthodontics and autophagy have complex mechanisms.However,existing research has only focused on exploring the role of autophagy in orthodontic tooth movement.Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement,as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways.

Objective:To investigate the effects of self-made Gujin Xiaoji Mixture combined with warming needle therapy on the clinical efficacy and immune function of patients with advanced non-small cell lung cancer (NSCLC) with qi and yin deficiency syndrome.Methods:This experiment was a randomized controlled trial study. 180 patients with advanced NSCLC qi and yin deficiency syndrome in the oncology centre of Qingdao Hospital of Traditional Chinese Medicine were selected as the observation subjects from March 2021 to August 2022, and were divided into 2 groups using the random number table method, with 90 cases in each group. The control group received conventional chemotherapy combined with Sintilimab injection, 21 days as a cycle, with a total of 4 cycles of treatment; and the observation group received Gujin Xiaoji Mixture combined with warming needle therapy based on the control group, 7 days as one course of treatment, with a total of 12 courses. Both groups were followed up for 12 months. The TCM syndrome scores were performed before and after treatment. The functional assessment of cancer therapy-lung (FACT-L) was used to evaluate the quality of life of patients; flow cytometry was used to detect the levels of CD3 +, CD4 +, CD8 + and NK cell, and the CD4 +/CD8 + ratio was calculated; adverse drug reactions and progression free survival of patients during treatment were observed and recorded, the efficacy of TCM syndrome and objective efficacy of solid tumors were evaluated. Results:After treatment, the observation group's post-treatment TCM syndrome score (5.67±1.99 vs. 7.12±2.31, t=-4.53) was lower than that of the control group ( P<0.001); mobility (23.03±2.80 vs. 20.69±2.46, t=5.96), daily living (23.06±2.56 vs. 20.71± 2.33, t=6.42), emotional status (18.44±2.32 vs. 16.12±2.71, t=6.18), and other factors (33.14±4.11 vs. 27.39±4.64, t=8.81) and total score (97.68±7.23 vs. 84.91±7.49, t=11.64) were higher than those in the control group ( P<0.01). In the observation group, after treatment, the levels of CD3 + [(65.14±6.06)% vs. (59.84±5.74)%, t=6.02], CD4 + [(40.09±4.09)% vs. (35.69±3.86)%, t=7.43], NK cell [(29.11±4.81)% vs. (22.38±4.51)%, t=9.68] and CD4 +/CD8 + [(1.52±0.27) vs. (1.14±0.12), t=12.63] were higher than those in the control group ( P<0.01), and CD8 + [(26.82±3.79)% vs. (31.76±4.65)%, t=-7.81] level was lower than that of the control group ( P<0.01). After treatment, the objective remission rate in the observation group was 7.8% (7/90), and the disease control rate was 87.8% (79/90), while the objective remission rate after treatment in the control group was 5.5% (5/90), and the disease control rate was 82.2% (74/90), and there were no statistical significance in the comparison of objective remission rate and disease control rate of the 2 groups ( χ2=0.09, 0.70, P=0.765, 0.407). The total effective rate after treatment was 62.2% (56/90) in the observation group and 34.4% (31/90) in the control group, and the difference between the 2 groups was statistically significant ( Z=-3.89, P<0.001). WBC [(4.27±1.12)×10 9/L vs. (3.84±1.11)×10 9/L, t=2.58] and haemoglobin [(119.93±17.25)g/L vs. (109.76±15.61)g/L, t=4.15] levels of the observation group were higher than those in the control group after treatment ( P<0.01). During follow-up, the median progression-free survival was 6.2 months in the observation group and 5.5 months in the control group patients, and the difference between the 2 groups was not statistically different ( t=0.11, P>0.05). Conclusion:The combination of Gujin Xiaoji Mixture with warming needle therapy can effectively improve the clinical symptoms of patients with advanced NSCLC with deficiency of qi and yin syndrome, improve the immunity and clinical efficacy of patients, alleviate the adverse effects of drugs, and prolong the progression-free survival period.

Objective:To investigate the initial high resolution CT (HRCT) manifestations and clinical features of imported COVID-19 in Guangzhou.Methods:A retrospective analysis of 91 COVID-19 patients admitted to the Guangzhou Eighth People's Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years,then their clinical features and HRCT characteristics were analyzed.Results:The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry cough in 39 cases). The first time HRCT showed that 24 cases with COVID-19 were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung.Conclusion:The initial images of COVID-19 in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of COVID-19 patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.