China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

[Secondary non-tuberculous mycobacterium infection in patients with bronchiectasis caused by Marfan syndrome].

In this article, we reported a 28-year-old female patient who presented with intermittent hemoptysis, cough, and sputum production. Laboratory tests showed no abnormalities in the blood counts or inflammatory markers, and the sputum cultures were negative. A chest computed tomography scan showed bronchiectasis associated with infection in the middle and lower lobes of the right lung and right pleural thickening. We performed bronchoalveolar lavage by bronchoscopy in the dorsal segment of the right lower lobe and found Mycobacterium avium intracellulare complex (MAC) by Next Generation Sequencing (NGS) of bronchoalveolar lavage fluid (BALF). The patient's symptoms improved significantly after anti-mycobacterium treatment and the extent of infection was reduced on imaging. To further identify the cause of bronchiectasis, the patient is tall and thin, with slender limbs. Cardiac color ultrasound showed the widening of aortic sinus. Her genetic testing of blood samples revealed the gene mutation in the FBN1 gene (c.4349G>A). Based on these results, she was diagnosed with Marfan syndrome.

A comprehensive analysis of nucleotide excision repair characteristics defines a novel prognostic signature for acute myeloid leukemia.

OBJECTIVE: Nucleotide excision repair (NER) has been associated with various types of malignant tumors. However, the precise roles of nucleotide excision repair-related genes (NERGs) in acute myeloid leukemia (AML) remain incompletely understood. Hence, this study aimed to develop a prognostic signature incorporating NERGs in AML, which could potentially predict patient outcomes. MATERIALS AND METHODS: By querying the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases, we acquired RNA-seq data and clinical information pertaining to AML. To identify differentially expressed NERGs (DE-NERGs), we employed the Wilcoxon rank-sum test. Based on the expression patterns of DE-NERGs with prognostic significance, patients were categorized into two subgroups. A prognostic signature was developed through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to compare the differentially expressed genes (DEGs) between these two groups. Additionally, a nomogram was constructed using multivariate analysis. The biological pathways involved were elucidated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA). RESULTS: We developed a prognostic model based on an 11-gene signature. Furthermore, the risk score derived from this model was demonstrated to independently serve as a prognostic marker for patients diagnosed with AML. CONCLUSIONS: Our prognostic model, based on NERGs, was developed and validated to provide insights into the onset and progression of AML and establish a foundation for more effective treatment. Our findings not only contribute to clinical decision-making but also underscore the significance of nucleotide excision repair. Furthermore, they may pave the way for the development of targeted therapeutic strategies specifically focused on this process.

[Choice of immediate breast reconstructive methods after modified radical mastectomy].

OBJECTIVE: To investigate the choice of immediate breast reconstructive methods and asso-ciated outcomes after modified radical mastectomy. METHODS: Retrospective analysis of patients undergoing immediate breast reconstruction after modified radical mastectomy in Peking University Third Hospital from January 2009 to May 2019. The reconstructive methods were summarized, and the clinical outcomes and the safety of immediate breast reconstruction were evaluated. RESULTS: One hundred and twenty-three patients were enrolled in this study. Different reconstructive methods were applied according to the clinical stage, the amount of skin removal, the size of contralateral breasts, the physical condition and the preference of the patients. Seventy-nine cases were performed with tissue expander/implant two-stage reconstruction, twenty-three cases received direct breast implant insertion, seven cases were applied for latissimus dorsi (LD) myocutaneous flap transfer combined with implant insertion, five cases were provided transverse rectus abdominis myocutaneous (TRAM) flap transfer, six cases underwent tissue expander/implant combined with endoscopic LD muscle flap transfer, and three cases chose tissue expander/deep inferior epigastric artery perforator (DIEP) flap transfer. The average follow-up time was (12.3±9.0) months (3.5-41.0 months). One patient with direct implant insertion had partial blood supply distur-bance of the mastectomy flap. One case had necrosis of distal end of TRAM zone Ⅳ. One patient with expander/DIEP reconstruction had partial fat liquefaction. And two cases had expander leakage at the end of the expansion period. The tumor local recurrence occurred in one patient, and the implant was finally removed. The outcomes were evaluated by Harris method, and 90.2% patients were good or above in shape evaluation. Among the patients with implant based reconstruction, there was no obvious capsular contracture, and most of the implants had good or fair mobility. CONCLUSION: It is safe and feasible of immediate breast reconstruction after modified radical mastectomy for appropriate cases. The reconstructive methods can be individualized according to the individual's different conditions. The appropriate reconstructive methods could achieve satisfactory results.

[Enterostomy based on abdominal wall tension and fascial locking: a theory of preventing stoma complications and parahernia].

No consensus on standardized technique of enterostomy creation has been made meanwhile high heterogeneity of surgical procedure exists in 'stoma creation' chapters of textbooks or atlases of colorectal surgery. The present article reviews the anatomy of tendinous aponeurotic fibers which is crucial for abdominal wall tension and integrity. Through empirical practice we hypothesize a procedure of enterostomy creation basied on abdominal wall tension plus anchor suture for fascia fixation which could theoretically decrease short-term stoma complication rates and long-term parastomal hernia rates. Surgical techniques are as followed: (1) preoperative stoma site mark for de-functioning ileostomy should be positioned at the lateral border of rectus abdominis muscle (RAM) to decrease the difficulty of stoma reversal and for permanent colostomy should be placed overlying the RAM to promote adhesion; (2)Optimal circular removal or lineal opening of skin, and avoid dissection of subcutaneous tissue; (3) Lineal dissection of natural strong fascia (rectus sheath) at stoma site and blunt separation of muscular fibers. The tunnel of the fascia should be made with appropriate size without undue tension. To prevent the formation of dead space, additional suturing at fascia layer is unnecessary. (4) Anchor suture for fascia fixation at two ends of fascia opening could be considered to avoid delayed fascia disruption and parastomal hernia. (5) After pull-through of ileum or colon loop, 4-8 interrupted seromuscular sutures could be placed to attach loop to skin. For ileostomy, self-eversion of mucosa can be successful in vast majority of cases and a Brooke ileostomy is not necessary. The efficacy and safety of this procedure should be tested in future trials.

[The value of serum estradiol concentration on the day of endometrial transformation in predicting the outcome of frozen-thawed embryo transfer in hormone replacement cycle].

To analyze whether the serum concentration of estradiol on the day of progesterone conversion could predict the pregnancy outcome of frozen-thawed embryo transfer in hormone replacement cycle. In this paper, a case-control study was conducted to retrospectively analyze the 230 cycles of hormone replacement therapy-frozen thawed embryo transfer(HRT-FET)conducted by the Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to December 2020. The concentration of serum estradiol was between 139.5-3 941.0 pg/ml. According to the percentile of serum estradiol concentration on the day of endometrial transformation, patients were divided into three groups: control group (<25th percentile, n=58), high estradiol group (25th-75th percentile, n=112) and ultra-high estradiol group (>75th percentile, n=60). Comparing the basic characteristics and pregnancy outcome of the three groups, the main observation index was the live birth rate, and the secondary observation index was the clinical pregnancy rate. F test and Kruskal-Wallis (H) test were used to compare the measurement data, and χ2 test was used to compare the counting data. The results showed that there was no significant difference in age, anti-Müllerian hormone(AMH), antral follicle count(AFC), body mass index(BMI), years of infertility and the proportion of primary infertility among the three groups(F=2.375, H=5.479, H=5.374, F=1.391, H=4.779, χ²=1.969, P>0.05). FET cycle treatment: There was no significant difference in the concentration of progesterone (P) before transformation, the thickness of endometrium on the day of transformation, the proportion of single embryo transfer and blastocyst transfer among the three groups (H=5.359, H=5.957, χ²=0.626, χ²=4.532, P>0.05). The days of estrogen administration before endometrial transformation in the three groups during the FET cycle were 13.0 (12.0, 14.0) days in the high estradiol group and 13.0 (12.0, 15.0) days in the ultra-high estradiol group, which were significantly longer than those in the control group 13.0(12.0, 13.3)days. The E2 concentration before intimal transformation in high estradiol group was 1 560.4 (1 170.2, 1 848.2) pg/ml, while that in ultra-high estradiol group was 2 420.9 (2 131.0, 2 849.2) pg/ml, which was significantly higher than that in control group 238.8 (206.9, 287.0) pg/ml. The pregnancy outcome of the three groups: the clinical pregnancy rate of the three groups was 37.9% in the control group, 51.8% in the high estradiol group and 40.0% in the ultra-high estradiol group, of which the high estradiol group had the highest clinical pregnancy rate, followed by the ultra-high estradiol group. But there was no significant difference among the three groups (χ²=3.853, P>0.05). The embryo implantation rate of the three groups was 19.3%, 25.0%, 32.8%, respectively, and the embryo implantation rate of the ultra-high estradiol group was the highest, but there was no significant difference among the three groups (χ²=5.544,P>0.05).The live birth rate of the three groups was 37.9%, 39.3%, 40.0%, respectively, and the difference was not statistically significant (χ²=0.05, P>0.05). A total of 14(13.5%) abortions occurred in 104 clinical pregnancies, all of which occurred in the high estradiol level group. Of the 104 clinical pregnancies, 24 (23.1%) had twin pregnancies, which occurred in the high estradiol level group (10 cases) and the ultra-high estradiol level group (14 cases). There were no twin pregnancies in the control group. Ectopic pregnancy occurred in 4 of 230 FET cycles (1.7%), 2 in control group and 2 in high estradiol group, and no ectopic pregnancy in ultra-high estradiol group.

[Disease spectrum analysis of children with inherited metabolic diseases detected by gas chromatography-mass spectrometry of urinary organic acids].

Objective: To investigate the spectrum of amino acid, organic acid, and fatty acid oxidative metabolic diseases in children diagnosed by detecting urinary organic acid levels using gas chromatography-mass spectrometry. Methods: From January 2005 to December 2021, clinical data of 2 461 children diagnosed with inherited metabolic diseases (IMD) by gas chromatography-mass spectrometry, in combination with tandem mass spectrometry and genetic testing in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. Results: Among 2 461 children, 1 446 were male and 1 051 were female. A total of 32 types of IMD were detected among 2 461 patients, which included 10 amino acid disorders in 662 cases (26.9%), 6 common diseases were hyperphenylalaninemia, citrin deficiency, ornithine carbamoyltransferase deficiency, maple syrup urine disease, alkaptonuria, and tyrosinemia-I, 17 types of organic acidemias in 1 683 cases (68.4%), 6 common diseases were methylmalonic acidemia, propionic acidemia, valeric acidemia-type Ⅰ, isovaleric acidemia, 3-methylcrotonyl-CoA carboxylase deficiency and multiple carboxylase deficiency and 5 fatty acid ß oxidative defects in 116 cases (4.7%), 2 common diseases were multiple acyl-CoA dehydrogenase deficiency and short-chain acyl-CoA dehydrogenase deficiency). Conclusion: Among the diseases diagnosed by analyzing urinary organic acid profiling with gas chromatography-mass spectrometry, the most common are organic acidemias, followed by amino acid disorders and fatty acid oxidation defects.

[NDRG2 inhibits tumorigenesis of hepatocellular carcinoma by regulating metabolism of phospholipids and triglyceride: a metabonomic analysis].

OBJECTIVE: To explore the role of the tumor suppressor gene NDRG2 in regulating lipid metabolism in hepatoma cells. METHODS: We analyzed the differential expression of NDRG2 gene between hepatocellular carcinoma tissues (n=809) and normal liver tissues (n=379) based on data from TNMplot database, and investigated the correlation between NDRG2 mRNA expression and the overall survival of the patients with hepatocellular carcinoma using THPA database, which was also used for analysis of NDRG2 expression levels in tumor cell lines for screening hepatoma cell lines. Human hepatoma cell line HepG2 was infected with a lentivirus containing NDRG2 cDNA, and the expression level of NDRG2 in the infected cells was detected using qPCR and Western blotting. Lipid metabolomics analysis was performed to analyze the regulatory effect of NDRG2 overexpression on lipid metabolism in HepG2 cells, and ELISA and Oil Red O staining were used to examine the changes in contents of phospholipids and triglyceride in NDRG2-overexpressing HepG2 cells. RESULTS: Analysis of the TNMplot database showed that NDRG2 expression level was significantly lower in hepatocellular carcinoma tissues than in normal liver tissues (P < 0.001). Analysis of THPA database showed that the patients with high NDRG2 mRNA levels had a longer survival time than those with low NDRG2 mRNA levels, and NDRG2 expression level was the highest in HepG2 cell line among the tumor cell lines. Metabolomics analysis showed that in HepG2 cells, NDRG2 overexpression led to changes in the contents of phospholipids, and among them lecithin PC, phosphatidyl glycerol PG, phosphatidyl ethanolamine PE, sphinophosphatidyl serine SM, and ceramide Cer exhibited significant changes. The results of ELISA and Oil Red O staining demonstrated that NDRG2 overexpression obviously reduced the contents of multiple phospholipids and significantly lowered the contents of triglyceride in HepG2 cells. CONCLUSION: NDRG2 regulates tumorigenesis of hepatocellular carcinoma by modulating the metabolism of phospholipids and triglyceride.

[Surveillance of Enterobius vermicularis infections among children in Shandong Province from 2016 to 2020].

OBJECTIVE: To investigate the prevalence and changing trend of Enterobius vermicularis infections among children in Shandong Province, so as to provide the scientific evidence for the adjustment and development of the enterobiasis control strategy. METHODS: Soil-borne nematodiasis surveillance sites were assigned in 51 counties (districts, cities) in Shandong Province from 2016 to 2020, and the E. vermicularis infections were detected using a modified Kato-Katz technique and the cellophane tape method among children at ages of 3 to 9 years living in these surveillance sites. The epidemiological profiles of E. vermicularis-infected children were descriptively analyzed. RESULTS: A total of 5 060 children at ages of 3 to 9 years were detected in 51 soil-borne nematodiasis surveillance sites in Shandong Province from 2016 to 2020, and the overall prevalence of E. vermicularis infections was 2.23%. The annual prevalence of E. vermicularis infections was 3.99% (26/651), 1.70% (14/824), 0.96% (8/837), 2.90% (45/1 552) and 1.67% (20/1 196) from 2016 to 2020, respectively, with a significant difference detected among years (χ2 = 21.455, P < 0.01). The prevalence of E. vermicularis infections was 1.25% (15/1 198), 1.85% (14/755), 3.18% (84/2 640) and 0 (0/467) among children from central, eastern, southern and northern Shandong Province (χ2 = 27.326, P < 0.01). In addition, there was no significant difference in the prevalence of E. vermicularis infections between male (1.98%, 56/2 831) and female children (2.56%, 57/2 229) (χ2 = 1.916, P > 0.05); however, there was age-specific prevalence of E. vermicularis infections among children (χ2 = 16.448, P < 0.05), with the greatest prevalence detected among children at ages of 6 years (3.18%, 25/786), and the lowest prevalence seen among children at ages of 3 years (0.75%, 6/800). CONCLUSIONS: The prevalence of E. vermicularis infections remained at a medium level among children at ages of 3 to 9 years in Shandong Province from 2016 to 2020, with region-specific prevalence found across the province. An integrated strategy is required for enterobiasis control.

[Efficacy and safety of giant emphysematous bulla volume reduction via medical thoracoscope].

Objective: To evaluate the efficacy and safety of giant emphysematous bulla (GEB) volume reduction via medical thoracoscope. Methods: This was a prospective, single-arm study conducted between July 2018 and September 2020 in Ri Zhao Hospital of Traditional Chinese Medicine. Patients who met the inclusion criteria were treated with GEB volume reduction via medical thoracoscope and were followed up to evaluate the efficacy and safety of the technique. According to comparison of preoperative and postoperative chest CT results, the self-designed evaluation criteria of imaging efficacy were as follows: complete or nearly complete disappearance of GEB (GEB volume reduction ≥90%), significant reduction of GEB (75%≤GEB volume reduction<90%), reduction of GEB (50%≤GEB volume reduction<75%) and no change (GEB volume reduction<50%). Results: A total of 47 patients were included, among whom 43 were males, with an age M (Q1, Q3) of 63.0 (55.0, 67.0). The CT results showed complete or nearly complete disappearance of GEB in 43 patients, significant reduction of GEB in 3 patients and reduction of GEB in 1 patient before discharge. The degree of dyspnea improved significantly (P<0.05). Arterial partial pressure of carbon dioxide (PaCO2) decreased from (48.2±8.4)mmHg (1 mmHg=0.133 kPa) to (45.4±7.3)mmHg (P<0.05). The 6-minute walk test (6MWT) increased from (245.6±162.4)m to (283.5±152.2)m (P<0.05). Six-month postoperative follow-up was completed in 24 patients, and CT results showed that the efficacy of volume reduction was continuous compared with that before discharge. GEB was further reduced or even disappeared in 3 of the cases. Besides, the degree of dyspnea, 6MWT (384.4±148.2)m and PaCO2 (42.7±6.6)mmHg were improved significantly (P<0.05). The oxygenation index (356.86±61.21)mmHg was significantly higher than that before surgery (295.20±67.16)mmHg and before discharge (294.50±76.69)mmHg (P<0.05). No perioperative deaths occurred. Conclusions: GEB volume can be completely eliminated or significantly reduced by this innovative technique, while PaCO2, the degree of dyspnea and exercise endurance can be significantly improved after operation. The 6-month follow-up after surgery showed that the above benefits continued, and that the oxygenation index improved significantly.

[The value of soluble thrombomodulin in evaluating endothelial injury in patients with kidney disease].

Objective: To evaluate the value of soluble thrombomodulin (sTM) in evaluating endothelial injury in patients with kidney disease. Methods: One hundred and thirty-three patients who first visited the Department of Nephrology of Beijing hospital for various reasons from September 2020 to January 2021 and 130 healthy people were collected and divided into groups according to age, gender, primary disease, complications and so on. The differences of sTM and serum creatinine in patients with different diseases and renal disease stages were analyzed. Results: For patients with chronic kidney disease (CKD), sTM increased significantly with the decrease of renal function. The level of sTM in patients with CKD stage 1-5 was (0.013±0.007), (0.019±0.010), (0.022±0.008), (0.027±0.008), (0.033±0.006)TU/L, respectively (F=21.005,P<0.05). There was no significant difference in the level of sTM between patients with non-CKD urinary tract infection (0.013±0.009) TU/L and patients with stage 1 CKD (t=1.023, P>0.05). No matter whether the patients were complicated with infection or cardiovascular disease, there was no significant difference in sTM level under the condition of serum creatinine matching (all P>0.05). In 4 patients with acute renal injury, serum creatinine returned to normal after active treatment, but sTM did not decrease significantly. Correlation analysis showed that there was a positive correlation between sTM and serum creatinine (r=0.697, P<0.01). Conclusion: sTM can evaluate the renal function damage of patients with CKD more early, and the level of sTM in patients with renal disease is more related to the degree of endothelial damage.

[Epidemiological characteristics of imported malaria in Shandong province, 2017-2018].

Objective: To understand epidemiological characteristics of imported cases of malaria in Shandong province and provide scientific basis for timely adjustment of prevention and control measures. Methods: The incidence data of malaria, case investigation data and case review data by Shandong Provincial Reference Laboratory for Malaria Diagnosis from 2017 to 2018 were collected. Software SPSS 18.0 was used for statistical analysis and software QGIS 2.18 was used for mapping. Results: A total of 442 imported cases of malaria were reported in Shandong from 2017 to 2018, and the main infection source was in Africa (97.96%, 433/442). All the 17 prefectures in Shandong reported imported malaria cases, mainly in Jining (88 cases), Yantai (65 cases), Weihai (46 cases), Qingdao (44 cases) and Dezhou (42 cases), accounting for 64.48% (285/442). The cases were distributed in 77.37%(106/137) of counties of the province. The cases were reported in every month without seasonal characteristics. The median (M) of time interval between onset and the first medical care seeking was 2 days, and the interquartile range (IQR) was 3 days. The M of time interval between the first medical care seeking and final diagnosis was 0 day, and the IQR was 3 days. The proportion of medical care seeking on onset day was only 27.83% (123/442). Only 69.68% (308/442) of cases were diagnosed with malaria in the first medical care seeking, and the diagnostic accuracy of medical institutions below the county level was lower than other medical institutions (all P<0.01). Only 51.13% (226/442) of cases were diagnosed with malaria in the first medical care seeking, the differences in the rates among medical institutions at different levels were not significant (P>0.05). Conclusions: The imported malaria in Shandong was characterized by a large number of cases, multiple infection sources and wide area distribution during 2017-2018. The awareness of timely medical care seeking in the cases was low, meanwhile the awareness and ability of malaria diagnosis and treatment in primary medical institutions were still inadequate. It is necessary to adjust the prevention and control measures accordingly.

[Pepsin and bile acids detection in saliva for the diagnosis of gastroesophageal reflux disease].

Objective: To identify the value of the detection of pepsin and bile acids in saliva for the diagnosis of gastroesophageal reflux disease(GERD). Methods: From January 2018 to June 2019, 104 GERD patients and 43 healthy people in Guangdong Provincial People's Hospital were recruited. The 104 patients of GERD group were divided into four sub-groups, including esophageal symptoms GERD group, extraesophageal symptoms GERD group, anxiety or depression group, non-anxiety and non-depression group. Saliva was collected on waking in morning and 2 h after finishing lunch. The concentration of the total pepsin(TPP) and total bile acids(TBA) from saliva was detected by ELISA method. Receiver operating characteristics analysis was used to identify the sensitivity and specificity of the saliva pepsin and bile acids detection. Results: The concentration of TPP in morning waking samples and postprandial samples in the GERD group was 27.1(9.7,50.3) µg/L and 32.4(14.0,58.7) µg/L, the concentration of TBA in postprandial samples was (18.4±2.3)µmol/L, and these levels were significantly higher than that of the control group [7.0(5.1, 9.1) µg/L, 7.4(5.2, 9.4) µg/L, (12.6±5.0)µmol/L](P<0.01). The concentration of TBA in morning waking samples had no significant difference between these two groups(P>0.05). The concentration of TPP and TBA had no significant difference among the four GERD sub-groups(P>0.05).Pepsin in postprandial saliva samples had moderate diagnostic value for GERD, when the saliva pepsin concentration in postprandial samples was higher than 41.33 µg/L, it had a sensitivity of 82.8% and a specificity of 73.3%. The bile acids in saliva had no significant diagnostic value for GERD. Conclusions: Pepsin detection in saliva has a high level of sensitivity and specificity for diagnosing GERD. However, bile acids in saliva has no significant diagnostic value for GERD.

Effect of imatinib on DOCA-induced myocardial fibrosis in rats through P38 MAPK signaling pathway.

OBJECTIVE: To explore the role of imatinib in desoxycorticosterone acetate (DOCA)-induced myocardial fibrosis in rats by the p38 mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: Normal group (n=20), DOCA induction group (n=20), and imatinib treatment group (treatment group, n=20) were set up. Then, the cardiac function was examined via magnetic resonance imaging (MRI) and echocardiography (ECG) on the 21st d after modeling. Alkaline phosphatase (ALP) and myocardial function index creatine kinase-MB (CK-MB) were detected. The enzyme-linked immunosorbent assay (ELISA) was performed to measure tumor necrosis factor-gamma (TNF-γ) and interleukin-6 (IL-6). Hematoxylin-eosin (HE) staining assay was carried out to observe the pathological changes in myocardial tissues. Quantitative Polymerase Chain Reaction (qPCR) and Western blotting were employed to measure the expression levels of important myocardial fibrosis-related genes [checkpoint kinase 1 (Chek1) and alpha-smooth muscle actin (α-SMA)], as well as genes and proteins of the p38 MAPK signaling pathway. RESULTS: In comparison with the normal group, DOCA induction group had significantly lowered fractional shortening (FS, %) and ejection fraction (EF, %), but overtly increased left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVESd), as well as levels of serum ALP, alanine aminotransferase (ALT), and CK-MB. Besides, the levels of TNF-γ, IL-6, and IL-1ß were notably raised in the DOCA induction group. HE staining results showed that myocardial injury was more severe in DOCA induction group. The results of the gene detection revealed that the expression levels of Chek1, α-SMA, p38 MAPK, and JNK were evidently higher in DOCA induction group than those in the imatinib treatment group (p<0.05), and the expression of p38 MAPK protein in the rat myocardial tissues was remarkably lower in the treatment group than that in the DOCA induction group (p<0.05). CONCLUSIONS: Imatinib can regulate the repair of myocardial injury caused by DOCA-induced myocardial fibrosis in rats by repressing the p38 MAPK signaling pathway.

Regorafenib and ginsenoside combination therapy: inhibition of HepG2 cell growth through modulating survivin and caspase-3 gene expression.

BACKGROUND: This work aimed to investigate the inhibitory effect of regorafenib in combination with ginsenoside on the growth of HepG2 liver cancer cells. METHODS: HepG2 liver cancer cells were divided into blank control group, regorafenib single-drug group, ginsenoside single-drug group, and regorafenib/ginsenoside combination group. Cells in the regorafenib single-drug group were treated with regorafenib at 0.25 mg/L, 0.5 mg/L, and 1 mg/L, respectively, while cells in the ginsenoside single-drug group were treated with ginsenoside at 5.0 mg/L, 10.0 mg/L, and 20.0 mg/L, respectively. HepG2 cell proliferation, expression of survivin mRNA, and the apoptotic effector caspase-3 in HepG2 liver cancer cells were assessed. RESULTS: An inhibitory effect on the growth of HepG2 liver cancer cells was observed for both the single-drug therapies and the combination therapy. The synergistic inhibitory effect presented by the combination therapy was dependent on the gradient concentration and treatment time. RT-qPCR results showed that both regorafenib and ginsenoside significantly reduced the expression of survivin mRNA in HepG2 liver cancer cells and the expression level of survivin mRNA in the regorafenib/ginsenoside combination group was much lower than those in the regorafenib single-drug group and ginsenoside single-drug group. The two drugs demonstrated synergistic inhibitory effect when used in combination. CONCLUSIONS: The findings in this study offered a theoretical insight into clinical use of regorafenib and ginsenoside for treatment of liver cancer.

Effects of lncRNA gm4419 on rats with hypertensive cerebral atherosclerosis through NF-κB pathway.

OBJECTIVE: To explore the effects of long non-coding ribonucleic acid (lncRNA) Gm4419 on rats with hypertensive cerebral atherosclerosis through the nuclear factor-kappa B (NF-κB) pathway. MATERIALS AND METHODS: Healthy male rats were selected and randomly divided into control group, model group (hypertensive cerebral atherosclerosis model), and lncRNA group (hypertensive cerebral atherosclerosis model + lncRNA injection). Neurological deficit scoring criteria, flow cytometry, Western blotting, and staining method were adopted to measure the differences in the neurological function score, NF-κB activity, and chemerin level of rats in the three groups. RESULTS: The neurological scores revealed that the neurological function of rats was not damaged in control group, while it was severely damaged in model group. However, the neurological function of rats was more severely damaged in lncRNA group than that in control group and model group, while the neurological function deficits were slighter in model group. In terms of NF-κB expression activity in mononuclear cells, the serum activity of NF-κB in control group appeared the lowest among the three groups and was significantly higher in lncRNA group than in model group. The serum chemerin level was evidently increased in model group compared with control group, while it was significantly decreased in lncRNA group compared with model group and control group. Moreover, the levels of NF-κB and chemerin were most evidently influenced in lncRNA group. CONCLUSIONS: Activating the NF-κB signal, lncRNA Gm4419 promotes the expression of chemerin signal, accelerates the apoptosis of nerve cells, and motivates the deterioration of hypertensive cerebral arteriosclerosis.

[Serum status and their changes of some vitamin substances and homocysteine in healthy subjects in Beijing].

Objective: To investigate serum status of folate, vitamin B(12), homocysteine (Hcy) and hydroxyvitamin D (25OHD) and their trends in different gender and age groups. Methods: This was a cross-sectional study. The enrolled subjects were those received medical examination in Beijing Hospital from September to November 2018 and were identified as appeared healthy persons. 1220 subjects were recruited and were divided into groups of young and middle age group (30-49 years, 50-59 years) and the elderly group (60-69 years, 70-79 years and ≥80 years). We measured folate, vitamin B(12), and 25OHD using electrochemiluminescence by chemiluminescence immunoassay. Hcy was measured by autobiochemical analyzer. Results: Total folate levels in male and female subjects were 7.16 (4.74-10.75) and 9.17 (6.49-13.55) µg/L respectively. Total vitamin B(12) levels in the male and female were 505.60 (386.80-700.90) and 582.60 (430.70-846.98) ng/L respectively. Hcy levels were 14.68 (12.25-18.58) and 11.29 (9.65-13.58) µmol/L. 25OHD levels were 21.60 (16.40-28.70) and 16.80 (12.30-24.15) µg/L respectively. Total folate and vitamin B(12) levels in female were higher than that in male subjects (Z=-7.796, -4.772, P<0.001). However, total Hcy and 25OHD levels in male were higher than that in female subjects (Z=-15.230, -8.447, P<0.001). Comparing with the substances in the above age groups, folate level in the elderly was lower than that in the younger age and middle age groups.However, vitamin B(12), 25OHD and Hcy levels were higher in the elderly groups. Furthermore, the levels of folate, vitamin B(12) and 25OHD were getting higher in the group of ≥80 years female compared with the rest of the age groups, but it turned lower in the male group of ≥80 years. Conclusions: There are some differences in the serum values of folate, vitamin B(12), Hcy and 25OHD among various age groups as well as between males and females. These should be considered in the development of national reference ranges.

Arotinoid trometamol inhibits arsenic trioxide-stimulated keratinocyte proliferation via the Wnt, Shh, and bone morphogenetic protein signaling pathways.

Arsenic acts as a human carcinogen and contributes to skin cancer via mechanisms that remain largely unknown. Recent evidence implicates the perturbation of Wnt, Shh and BMP signals as a potential mechanism. We initiated studies to examine gene expression changes in these signaling pathways. Meanwhile, the antagonistic effect of retinoic acid was explored. In this study, HaCaT and NHEK cells were treated with arsenic trioxide (As2O3) alone or in combination with arotinoid trometamol (retinoic acid receptor agonist). Flow cytometric analysis, PCR array and Western blot were used to determine the potential mechanism and signaling pathways associated with arsenic carcinogenesis. The results showed that low concentration As2O3 could stimulate keratinocyte proliferation, and arotinoid trometamol inhibited the process via regulating the expression of about 20 genes. These genes included components of Wnt signaling (CSNK1A1L, CTNNB1, SFRP1, Wnt10B, Wnt11, Wnt16, Wnt5A, Wnt8A), Shh signaling (C6orf138, HHIP, PTCHD1) and BMP signaling pathway (BMP2, BMP7). The changes of some differentially expressed genes of these signaling pathways in As2O3 treatment group were counteracted by the subsequent arotinoid trometamol treatment. Our data suggest that dysregulation and cross-talk of Wnt, Shh and BMP signals play great roles in the process of arsenic-induced carcinogenesis, which could be antagonized by arotinoid trometamol.