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ObjectiveTo obtain the prevalence of sarcopenia in middle-aged and elderly people in Urumqi based on the 2020 updated based on the 2020 updated Consensus Report 2019 of Asian Working Group for Sarcopenia （AWGS2019）， and to further explore the association between sarcopenia and metabolic syndrome （MS）. MethodsA total of 1 438 middle-aged and elderly people （aged≥50 years） in Urumqi from July 2018 to January 2019 were selected as the research subjects. Data were collected by questionnaire survey， physical examination and laboratory test. Skeletal muscle mass，grip strength and 4 m walking speed were used to represent muscle mass， muscle strength and body function， respectively. Bioelectrical impedance analysis （BIA） was used to measure human body components. Based on the diagnostic criteria of sarcopenia recommended by AWGS2019， the prevalence of sarcopenia in people over 50 years old was obtained. Multivariate logistic regression model was used to explore the correlation between sarcopenia and MS in middle-aged and elderly people of different genders. ResultsThere were 194 patients with sarcopenia， with a prevalence of 13.49%. The prevalence was 15.56% in males and 12.12% in females. There was no significant difference in the prevalence of MS between male sarcopenia group （40.45%） and non-sarcopenia group （38.92%）， while the prevalence of MS in female sarcopenia group （39.04%） was higher than that in non-sarcopenia group （27.56%）. Multivariate logistic regression analysis showed that sarcopenia was a related factor of MS. Compared with non-sarcopenia， the risk of MS in male sarcopenia group was higher （OR=2.11，95%CI： 1.15‒3.88 ）. ConclusionSarcopenia increases the risk of MS in middle-aged and elderly people， with a greater risk in men. Fully understanding of sarcopenia is helpful to early identify high-risk groups of MS and prevent the occurrence of MS.
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Objective:To optimize the challenge scheme for establishing a stable mouse model of Artemisia annua pollen-induced allergic rhinitis. Methods:BALB/c mice were subcutaneously injected with 0.1 ml allergen extract containing 20 μg/ml Art a1 from Artemisia pollen on 1 d, 4 d and 7 d. One week after the sensitization, these mice were divided into three groups and intranasally challenged with Artemisia annua pollen allergen extract containing 500 μg/ml Art a1 for 7 (7 d group), 10 (10 d group) and 14 (14 d group) consecutive days, respectively. The first challenge was followed by another 7 days of challenge every four weeks. Blank control group was set up through sensitizing and challenging BALB/c mice with normal saline. Behavioral changes and nasal pathological changes were observed. The changes in humoral and cellular responses were also detected. After the first challenge cycle was decided, the challenge frequency was further optimized. Results:After the first challenge, the allergic symptoms of mice in 10 d group were significantly severe than those in 7 d and 14 d groups, and the levels of serum specific IgE antibody in 10 d and 14 d groups were significantly higher than that in 7 d group. After the second challenge, the mice in the three model groups still had obvious allergic symptoms as compared with the blank control group. There were obvious pathological changes in the nose, including epithelial cell proliferation, turbinate enlargement and inflammatory cell increase. Moreover, the level of serum specific IgE antibody increased significantly and the proliferation of antigen-specific IL-4 and IL-6 lymphocytes was significantly up-regulated, especially in 10 d and 14 d groups. The frequency of challenge had a great impact on the stability of the allergic model. The allergic symptoms of sensitized mice challenged every two weeks were significantly severe than those of mice challenged every four weeks and the level of serum antigen-specific antibody was also higher.Conclusions:This study optimized the first challenge cycle and challenge frequency for establishing a mouse model of Artemisia annua pollen-induced allergic rhinitis, which provided reference for the establishment of drug efficacy evaluation system for desensitization therapy.
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Cardiovascular diseases， with high incidence and high mortality， belong to the category of "chest impediment and heart pain" in traditional Chinese medicine （TCM）. Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills， one of the National Essential Drugs， is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease （Qi deficiency and blood stasis syndrome）. This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi， activate blood， and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow， regulating immune functions， alleviating inflammation， detoxifying， and tranquilizing mind. Clinically， it is suitable for patients with angina pectoris caused by the lack of heart Yang， chest tightness， shortness of breath， palpitation， fear of cold for limbs and so on， especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports， this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets， location and links. Furthermore， we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research， aiming to provide data support and evidence for the clinical application of this medicine.
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@#Non-alcoholic fatty liver disease (NAFLD) is a series of chronic liver diseases strongly associated with the metabolic disorder with an increasing rate of worldwide prevalence.Due to its complicated pathogenesis, only Saroglitazar has been approved by Indian Drug Controller General (DCGI) as a PPAR-α/γ dual agonist to treat non-cirrhotic non-alcoholic steatohepatitis.Combination therapy, which can target same or different signaling pathways of NAFLD pathogenesis, has been developed to achieve synergistic therapeutic efficacy.Currently, small-molecule drug combination, RNAi combination therapy, and chemogene therapy are proposed as promising strategies in NAFLD treatment.In addition, designing a smart, safe and effective drug delivery system is key to realizing the druggability, clinical translation and industrialization of small molecule drugs and gene drugs.This review summarizes the research status and delivery system of small-molecule drug combination, RNAi combination therapy, and chemogene therapy, in the hope of providing some novel insight for the treatment of NAFLD.
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OBJECTIVE To explore the the reg ulation of intestinal flora and effects of Qingjie huagong decoction on intestinal mucosal barrier in severe acute pancreatitis （SAP）mode rats . METHODS SAP rat model was induced by intraperitoneal injection of caerulein and lipopolysaccharide.The survival state of rats in each group were observed.The levels of serum amylase ，interleukin 10（IL-10），IL-18 and IL- 1β in serum were all detected. The pathological changes of pancreatic and small intestinal tissue were observed. The expressions of Occludin，ZO-1 and HMGB1 were detected in small intestinal tissue of rats. The structure and relative abundance of intestinal microflora in rats were detected by 16S rRNA high throughput sequencing. RESULTS After the intervention of Qingjie huagong decoction ，abdominal distension symptoms of SAP model rats were significantly relieved ，and their mental state recovered better ；the levels of serum amylase and IL- 18 in serum were decreased significantly （P＜0.05），while the level of IL- 10 was increased significantly （P＜0.05）. The necrotic area of pancreatic tissue and the infiltration of inflammatory cells were reduced ， the degree of intestinal epithelial cell structural disorder was alleviated ，and the shedding of intestinal mucosal epithelium was reduced.The protein expression of HMGB 1 in small intestinal tissue was decreased significantly （P＜0.05），and the protein expression of Occludin and ZO- 1 were increased significantly . Results of 16S rRNA high throughput sequencing showed that Qingjie huagong decoction could increased the relative abundance of probiotics such as Bacteroidea and Lactobacillus in rat intestine ，reduced the colonization of harmful bacteria such as Firmicutes. CONCLUSIONS Qingjie huagong decoction can improve the intestinal barrier by up-regulating the expression of Occludin and ZO- 1 in small intestinal tissue and down-regulating the protein expression of HMGB 1. It can also adjust the relative abundances of different flora to protect the intestinal tract.
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Objective: To explore the application value of T lymphocyte subsets combined with procalcitonin (PCT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and white blood cell count (WBC) in the auxiliary diagnosis and prognosis evaluation of sepsis. Methods: In a retrospective study, seventy-two patients with sepsis diagnosed and treated in Tianjin First Central Hospital from June 2018 to April 2021 were selected as the research objects, and included in the sepsis group were 46 males and 26 females, aged 68 (57.3, 80.3) years. In addition, 111 patients with local infection admitted to hospital during the same period were included in the local infection group, including 62 males and 49 females, aged 68 (51, 77) years. Sepsis patients were divided into survival group (43 cases) and death group (29 cases) according to the 28-day outcome. CD3+, CD4+, CD8+, CD4+/CD8+ ratio were detected by flow cytometry within 24 h after admission, PCT was detected by ELISA, CRP was detected by immunoturbidimetry, blood routine examination, blood lactic acid (Lac) and oxygen partial pressure (PO2) were detected by instrumental method. Multivariate Logistic regression analysis was used to evaluate the correlation between each indicator and sepsis, and receiver operating characteristic curve (ROC) was drawn to evaluate the diagnostic value of each indicator for sepsis. Multivariate Logistic regression analysis and Kaplan Meier survival analysis were used to evaluate the prognostic value of each index for patients with sepsis. Results: Peripheral blood CD3+, CD4+, CD8+, CD4+/CD8+ ratio and PLT in sepsis group were significantly lower than those in local infection group(Z=-8.184,P<0.001;Z=-7.210,P<0.001;Z=-5.936,P<0.001;Z=-2.700,P=0.007;Z=-6.381,P<0.001); PCT, CRP, NLR and Lac levels were significantly higher than those in local infection group(Z=-8.262,P<0.001;Z=-3.094,P=0.002;Z=-9.004,P<0.001;Z=-4.770,P<0.001). Multivariate Logistic regression model showed that PCT, NLR, CD3+, CD8+, CD4+/CD8+ were independent risk factors for sepsis. According to ROC curve analysis, AUC of sepsis patients diagnosed by each indicator were 0.862, 0.894, 0.858, 0.760 and 0.618, respectively. The cut-off values were 3.075 ng/ml, 10.715, 44.935×109/L, 27.463×109/L and 0.750, respectively. The NLR sensitivity was 80.6%, and the CD3+ specificity was 94.6%. The AUC of combined detection of PCT and NLR was 0.947, sensitivity was 87.5% and specificity was 91.9%. The combined detection AUC of PCT, NLR, CD3+, CD4+/CD8+ was 0.958, the sensitivity and specificity were 90.3% and 91.0% respectively(P<0.001). PCT and Lac in death group were significantly higher than those in survival group(Z=-2.302,P=0.021;Z=-3.095,P=0.002);Peripheral blood CD4+/CD8+ levels were significantly lower than those in survival group(Z=-3.691,P<0.001),Multivariate Logistic regression model showed that CD4+/CD8+ ratio was an independent risk factor for 28 d mortality in patients with sepsis (P<0.001). The ROC curve showed that the AUC was 0.758, and the Youden index reached the maximum when the cut-off value was 1.27, the sensitivity and specificity were 79.3% and 60.5%, respectively. Compared with patients with CD4+/CD8+ ≥1.27, 28-day mortality was significantly increased in patients with CD4+/CD8+<1.27 (P=0.032). Conclusion: The combined detection of PCT, NLR, CD3+ and CD4+/CD8+ can improve the auxiliary diagnostic efficiency of sepsis, and the ratio of CD4+/CD8+ in peripheral blood may have certain predictive value for the prognosis of sepsis.
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Aged , C-Reactive Protein/analysis , Female , Humans , Male , Middle Aged , Procalcitonin , Retrospective Studies , Sepsis/diagnosis , T-Lymphocyte Subsets/chemistryABSTRACT
This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.
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Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Network Pharmacology , Prediabetic State/geneticsABSTRACT
Objective@#To investigate the prevalence of postmenopausal osteoporosis (PMOP) and analyze its influencing factors among women at ages of 50 to 59 years in Dali Bai Autonomous Prefecture, Yunnan Province, so as to provide insights into the prevention of PMOP among menopausal women.@*Methods@#Bai Ethnic menopausal women at ages of 50 to 59 years who received healthy examination at the Center of Healthy Examination, Dali Prefecture People's Hospital from June 2017 to May 2021 were selected as the study subjects, and subjects' demographic characteristics, living habits, history of diseases, family history of osteoporosis and history of parturition were collected using self-designed questionnaires. The height, body weight and bone density were measured, and fasting blood glucose, vitamin D3, blood lipids and liver functions were detected. The factors affecting the development of PMOP were identified using a multivariable logistic regression model.@*Results@#Totally 2 000 questionnaires were allocated, and 1 584 valid questionnaires were recovered, with an effective recovery rate of 79.20%. The respondents had a mean age of ( 56.22±2.61 ) years, and mean body mass index ( BMI ) of ( 24.62±2.35 ) kg/m2. There were 497 respondents ( 31.38% ) with a family history of osteoporosis, and the prevalence of PMOP was 20.64%. Multivariable logistic regression analysis identified age ( OR=1.135, 95%CI: 1.074-1.196 ), age of menarche ( OR=1.138, 95%CI: 1.059-1.217 ), duration of menopause (OR=1.425, 95%CI: 1.228-1.622), number of parturition ( >2, OR=5.036, 95%CI: 2.972-7.101 ), smoking ( OR=2.594, 95%CI: 1.767- 3.421 ), alcohol consumption ( OR=2.051, 95%CI: 1.503-2.598 ), family history of osteoporosis ( OR=2.540, 95%CI: 1.769-3.311 ), hypertension ( OR=1.492, 95%CI: 1.406-1.578 ), diabetes ( OR=1.774, 95%CI: 1.581-1.967 ), total cholesterol ( OR=1.483, 95%CI: 1.251-1.716 ), triacylglycerol ( OR=1.801, 95%CI: 1.576-2.026 ), low-density lipoprotein cholesterol ( OR=1.614, 95%CI: 1.498-1.731 ), fasting blood glucose ( OR=1.192, 95%CI: 1.077-1.307 ), BMI ( OR=0.934, 95%CI: 0.862-0.993 ), outdoor activity ( ≥1 time/week, OR: 0.413-0.549, 95%CI: 0.329-0.637 ), age of menopause ( OR=0.909, 95%CI: 0.841-0.977 ), daily intake of calcium ( ≥600 mg, OR: 0.493-0.644, 95%CI: 0.389-0.786 ), vitamin D3 level ( ≥20 ng/mL, OR: 0.604-0.719, 95%CI: 0.523-0.853 ) and high-density lipoprotein cholesterol ( OR=0.658, 95%CI: 0.550-0.767 ) as factors affecting the development of PMOP.@*Conclusions @#The prevalence of PMOP in Dali Bai Autonomous Prefecture is similar to the nationwide level in China, and old age, smoking, alcohol consumption, a family history of osteoporosis and high blood lipid levels may increase the risk of PMOP.
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Ultra high performance liquid chromatography tandem linear ion trap orbitrap mass spectrometry (UHPLC-LTQ-orbitrap-MS) was applied to analyze and identify flavonoids and phenylethanoid glycosides in the Tibetan herb Lagotis brevituba Maxim. A method of data-dependent scan coupling with dynamic exclusion was developed for analyzing flavonoids and phenylethanoid glycosides under positive and negative ion mode of electrospray ionization (ESI). The compounds of Lagotis brevituba Maxim. were systematically identified through exact molecular mass, fragmentation patterns, retention time and reported references. A total of 167 compounds were detected, of which 84 were flavonoids and 83 were phenylethanoid glycosides, which greatly enriched the number and types of flavonoids and phenylethanol glycosides in Lagotis genus medicinal plants. Baohuoside Ⅰ, 4 disaccharide O-glycoside flavonoids (composed of deoxyhexose and glucuronic acid), 9 C-glycoside flavonoids, 15 tetrasaccharide phenylethanoid glycosides and 5 phenylethanoid glycosides with substituents on the β-position of the phenylethyl group were identified in Lagotis genus medicinal plants for the first time. This study provides scientific support for elucidating the material basis and improving the quality control of Lagotis brevituba Maxim.
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Background Diabetes is a major threat to public health across the world. Studies have shown that exposure to p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) is closely related to the occurrence of type 2 diabetes mellitus. However, the relevant molecular mechanism is not clear. Objective To investigate the effects of p,p'-DDE on H19 differentially methylated region (DMR) methylation and insulin secretion of rat insulinoma cells (INS-1 cells). Methods INS-1 cells were cultured with different concentrations (0, 3.125, 6.25, 12.5, 25, 50, and 75 µmol·L−1) of p,p'-DDE for 24 h, and the viability of INS-1 cells was detected by CCK-8 method. INS-1 cells were exposed to 0, 12.5, 25, and 50 µmol·L−1 p,p'-DDE for 24 h in subsequent experiments. The methylation levels of 24 CpG sites in H19 DMR were analyzed by bisulfite genomic sequencing. The expression levels of insulin-like growth factor 2 (IGF2) mRNA were detected by real-time quantitative PCR. The expression levels of IGF2 and insulin-like growth factor-1 receptor (IGF1R) proteins were detected by Western blotting. The insulin secretion function of INS-1 cells was determined by glucose-stimulatedinsulin secretion test (5 and 25 mmol·L−1 glucose, respectively). Results Compared with the control group, the viability of INS-1 cells increased significantly after treatment with 12.5 µmol·L−1 p,p'-DDE; however, it was significantly inhibited after treatment with 50 or 75 µmol·L−1 p,p'-DDE (P<0.01); therefore, 50 µmol·L−1 was chosen as the maximum concentration of exposure for subsequent experiments. The 25 µmol·L−1 p,p'-DDE treatment decreased the methylation levels of CpG18 and CpG22-CpG24 sites in H19 DMR, and the 50 µmol·L−1 p,p'-DDE treatment decreased the methylation levels of CpG10-CpG24 sites (P<0.05 or P<0.05). Multiple concentrations (12.5, 25, and 50 µmol·L−1) of p,p'-DDE down-regulated the mRNA and protein relative expression levels of IGF2 and the protein relative expression levels of IGF1R. The transcription level of IGF2 decreased to 67.8%, 68.6%, and 62.5% of the control group, the protein level of IGF2 decreased to 73.3%, 79.5%, and 80.9% of the control group, and the protein level of IGF1R decreased to 54.8%, 25.6%, and 12.9% of the control group, respectively (P<0.01). In the high glucose context, p,p'-DDE at selected concentrations inhibited the insulin secretion levels to 85.0%, 58.6%, and 49.5% of the control group, respectively (P<0.01). Conclusion p,p'-DDE could down-regulate methylation level of H19 DMR, interfere the IGF2/IGF1R signaling pathway, and inhibit insulin secretion of islet cells.
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Background Occupational noise-induced hearing loss (NIHL) is one of the most prevalent occupational diseases in the world. With the development of industry, noise sources in the workplace have become increasingly complex. Objective To apply kurtosis-adjusted cumulative noise exposure (CNE) to assess the occupational hearing loss among furniture manufacturing workers, and to provide a basis for revising noise measurement methods and occupational exposure limits in China. Methods A cross-sectional survey was conducted to select 694 manufacturing workers, including 542 furniture manufacturing workers exposed to non-Gaussian noise, and 152 textile manufacturing workers and paper manufacturing workers exposed to Gaussian noise. The job titles involving non-Gaussian noise were gunning and nailing, and woodworking, while those involving Gaussian noise were weaving, spinning, and pulping. High frequency noise-induced hearing loss (HFNIHL) and noise exposure data were collected for each study subject. Noise energy metrics included eight-hour equivalent continuous A-weighted sound pressure level (LAeq,8 h) and CNE. Kurtosis was a noise temporal structure metric. Kurtosis-adjusted CNE was a combined indicator of noise energy and temporal structure. Results The age of the study subjects was (35.64±10.35) years, the exposure duration was (6.71±6.44) years, and the proportion of males was 75.50%. The LAeq,8 h was (89.43±6.01) dB(A). About 81.42% of the study subjects were exposed to noise levels above 85 dB(A), the CNE was (95.85±7.32) dB(A)·year, with a kurtosis of 99.34 ± 139.19, and the prevalence rate of HFNIHL was 35.59%. The mean kurtosis of the non-Gaussian noise group was higher than that of the Gaussian noise group (125.33±147.17 vs. 5.86±1.94, t=−21.04, P<0.05). The results of binary logistic regression analysis showed that kurtosis was an influential factor of workers' HFNIHL after correcting for age, exposure duration, and LAeq,8 h (OR=1.49, P<0.05). The results of multiple linear regression analysis showed that the effects of age, exposure duration, LAeq,8 h, and kurtosis on noise-induced permanent threshold shift at frequencies of 3, 4, and 6 kHz of the poor hearing ear were statistically significant (all P<0.05). The results of chi-square trend analysis showed that when CNE ≥ 90 dB(A)·year, the HFNIHL prevalence rate elevated with increasing kurtosis (P<0.05). The mean HFNIHL prevalence rate was higher in the non-Gaussian noise group than in the Gaussian noise group (31.7% vs. 22.0%, P<0.05). After applying kurtosis-adjusted CNE, the linear equation between CNE and HFNIHL prevalence rate for the non-Gaussian noise group almost overlapped with that for the Gaussian noise group, and the mean difference in HFNIHL prevalence rate between the two groups decreased from 9.7% to 1.4% (P<0.05). Conclusion Noise kurtosis is an effective metric for NIHL evaluation. Kurtosis-adjusted CNE can effectively evaluate occupational hearing loss due to non-Gaussian noise exposure in furniture manufacturing workers, and is expected to be a new indicator of non-Gaussian noise measurement and assessment.
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Objective:To prospectively guide the change of chemotherapy regimen in mouse 5-fluorouracil (5-FU) resistance subcutaneous xenograft tumor model derived from gastric cancer patients by the early changes of MRI apparent diffusion coefficient (ADC), and to compare the difference of tumor load between ADC guided dressing change group and volume guided dressing change group.Methods:From January to June 2020, thirty patient-derived xenografts mouse models were established using 5-FU resistant gastric cancer cells coming from patients, and were randomly divided into experimental group and control group by AdaBoost algorithm, with 15 mice in each group. On the 26th day after transplantation, all mice began chemotherapy with 5-FU as the first-line chemotherapy drug, and underwent MR examination once every two days, including T 2WI and diffusion weighted imaging (DWI). Volumes of tumors were measured using an open-source software ITK-SNAP and values of ADC were measured on ADC maps. According to the change rate of tumor ADC value in the experimental group and the tumor volume growth rate in the control group, the replacement time of chemotherapy drugs was determined, and 5-FU was replaced by paclitaxel. The end point of the experiment was the day that the mice entered the cachexia state. Independent-sample t test was used to compare the difference of tumor load between the two groups. Results:After 5-FU treatment, the ADC value of the two groups both increased. The ADC value began to decline on the 4th day after chemotherapy, and the experimental group continued chemotherapy with paclitaxel instead of 5-FU at this time point. The tumor volume growth rate of the control group increased significantly on the 6th day after chemotherapy (from 8.6% to 16.1%), and the control group used paclitaxel instead of 5-FU chemotherapy at this time point. The observed end point was on the 18th day after chemotherapy. The tumor load of the experimental group [(1.82±0.09) cm 3] was lower than that of the control group [(2.01±0.09) cm 3], and the difference was statistically significant ( t=2.25, P=0.033). On the 16th day after chemotherapy in the experimental group and the 18th day after chemotherapy in the control group, the time of paclitaxel administration in both groups was 12 days. The tumor load in the experimental group [(1.61±0.12) cm 3] was also lower than that in the control group [(2.01±0.09) cm 3], and the difference was statistically significant ( t=2.03, P=0.040). Conclusions:For the subcutaneous transplantation model of 5-FU resistant gastric cancer mice, according to the early changes of tumor ADC value after chemotherapy, the replacement of chemotherapy drugs can obtain a lower tumor load, suggesting that it is a feasible method to optimize the chemotherapy regimen.
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Objective:To investigate the level of gingival crevicular fluid and serum gingival sulcus fluid Dickkopf-1 (DKK-1), macrophage inflammatory protein-1α (MIP-1α) and interleukin (IL)-17 in patients with chronic periodontitis and their clinical significance.Methods:80 patients with chronic periodontitis (observation group) and 40 healthy periodontal subjects (control group) were prospectively selected. The gingival index (GI), bleeding index (BI), probe depth (PD), loss of attachment (AL) levels were compared between the two groups. The IL-6, IL-8, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), DKK1, MIP-1α and IL-17 levels in the gingival sulcus fluid and serum of the two groups were compared, and the correlation of DKK-1, MIP-1α and IL-17 levels with periodontal indexes and inflammatory factors in the observation group were analyzed. The DKK-1, MIP-1α and IL-17 levels in the gingival crevicular fluid and serum before and after treatment were compared among the patients with different disease degrees.Results:The levels of GI, BI, PD and AL in the observation group [(2.11±0.36)points, (3.76±0.65)points, (4.56±0.78)mm, (4.06±0.49)mm, respectively] were higher than those of the control group [(0.53±0.08)points, (1.61±0.33)points, (2.13±0.29)mm, 0 mm, respectively] (all P<0.05). The levels of IL-6, IL-8, TNF-α, DKK-1, MIP-1α and IL-17 in gingival crevicular fluid of the observation group [(65.23±9.30)ng/L, (310.19±42.95)ng/L, (40.46±9.70)ng/L, (13.70±3.62)μg/L, (19.67±8.14)μg/L, (315.84±53.76)pg/μl] were higher than those of the control group [(36.81±5.61)ng/L, (178.21±25.73)ng/L, (26.43±5.76)ng/L, (7.41±2.02)μg/L, (6.23±1.99)μg/L, (266.64±46.27)pg/μl, respectively] (all P<0.05). The serum levels of IL-8, TNF-α, DKK-1, MIP-1α and IL-17 in the observation group were also higher than those in the control group (all P<0.05). In the observation group, the levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum were positively correlated with eriodontal indexes (GI, BI, PD, AL) and the IL-8 and TNF-α levels (all P<0.05). In the observation group, the levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum of mild patients were lower than those of moderate to severe patients, and the levels of DKK-1, MIP-1α and IL-17 in mild and moderate to severe patients after treatment were also lower than those before treatment, with statistically significant difference (all P<0.05). Conclusions:The levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum of patients with chronic periodontitis are increased, which are closely related to the occurrence and development of chronic periodontitis. Detection of these indicators has certain significance for the diagnosis and treatment of the disease.
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Objective:To investigate the relationship between T-2 toxin, deoxynivalenol (DON) induced differentially expressed genes in human chondrocytes and Kashin-Beck disease (KBD), and to search for potential molecular markers of KBD.Methods:Gene microarray profiling was used to analyze the differentially expressed genes induced by T-2 toxin (0.01 μg/ml) and DON (1.0 μg/ml) in normal human chondrocytes, and the differences and similarities between them and the differentially expressed genes in KBD chondrocytes were compared. KEGG pathway enrichment analysis was performed on differentially expressed genes in each group. And the expression patterns of KBD susceptibility genes in T-2 toxin and DON induced human chondrocytes were further compared and analyzed.Results:Gene microarray profiling analysis showed that there were 882 (349 up-regulated genes, 533 down-regulated genes) and 2 118 differentially expressed genes (1 124 up-regulated genes, 994 down-regulated genes) in human chondrocytes induced by T-2 toxin and DON compared with normal control cells, respectively. Compared with differentially expressed genes in KBD chondrocytes, the genes with the same expression trend included B cell translocation gene 1 (BTG1), G protein signaling regulatory protein 5 (RGS5), fatty acid binding protein 4 (FABP4) and key protein senescence 1 (FBLN1), the same KEGG pathway including p53, extracellular matrix receptor interaction and phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Both T-2 toxin and DON induced human chondrocytes to up-regulate the expression of KBD susceptibility gene growth differentiation factor 5 (GDF5) and down-regulate the expression of collagen type ⅨA1 (COL9A1).Conclusion:The BTG1, RGS5, FABP4, FBLN1, GDF5 and COL9A1 genes play an important role in the pathogenesis of KBD and can be used as potential molecular markers for the pathogenesis of KBD.
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Objective:To explore the effect of mini-clinical evaluation exercise (Mini-CEX) combined with simulation teaching + case-based learning (CBL) in pediatric clinical teaching.Methods:A total of 60 medical students who practiced in Department of Pediatrics, Affiliated Hospital of Jining Medical College from August 2019 to August 2020 were selected as the research objects. According to different teaching methods, they were divided into control group ( n=30) and observation group ( n=30). The control group received traditional teaching, and the observation group received Mini-CEX combined with simulated teaching + CBL. The assessment results, comprehensive ability of medical interview, critical thinking ability and teaching satisfaction of the two groups were compared. SPSS 20.0 was performed for t-test and Chi-square test. Results:The test scores and total scores of the observation group were significantly higher than those of the control group ( P<0.05). After teaching, the Mini-CEX scores, the CTDI-CV (critical thinking disposition inventory Chinese version) scores and the total scores of the two groups increased significantly, and the above scores were significantly higher in the observation group than the control group ( P<0.05). The scores of the teaching program satisfaction questionnaire in the observation group were significantly higher than those in the control group ( P<0.05). Conclusion:The application of Mini-CEX combined with simulation teaching + CBL in pediatric clinical teaching can help to cultivate the medical interview ability, clinical practice ability and critical thinking ability of interns, improve the examination results, and improve the teaching satisfaction.
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Objective:To analyze the effect of behavior-oriented teaching in the teaching of pediatric nursing interns.Methods:A total of 63 pediatric nursing interns from March 2018 to December 2019 were selected as research objects. According to their admission, they were divided into control group ( n=31) and observation group ( n=32). The control group was taught by routine nursing teaching, and the observation group was taught by behavior-oriented teaching. After one month of intervention, the mastery of professional knowledge and the core competence of nursing interns were compared. Fatigue scale (FS-14) and mental health symptom checklist 90 (SCL-90) were used to evaluate their clinical nursing stress. SPSS 22 0 for t test and chi-square test. Results:The scores of nursing interns in the observation group were higher than those in the control group [(88.29±10.42) vs. (82.56±9.03)], with statistically significant differences ( P<0.05). After learning, the score of core competency inventory for registered nurse (CIRN) of nursing students in the observation group was higher than that in the control group ( P<0.05). After learning, the scores of FS-14 and SCL-90 in the observation group were lower than those in the control group, and the difference was statistically significant ( P<0.05). Conclusion:The application of behavior-oriented teaching can improve the professional knowledge and nursing skills of pediatric nursing interns, improve their core competence, alleviate their work pressure, and improve the quality of nursing teaching.
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Objective:To determine whether the blood urea nitrogen to serum albumin (B/A) ratio was a useful prognostic factor of mortality in the patients with acute non-variceal upper gastrointestinal bleeding (ANVUGIB).Methods:Totally 1 120 patients with acute upper gastrointestinal bleeding (VUGIB) admitted to the Emergency Department from January 2019 to December 2021 were prospectively and continuously collected and 449 eligible patients with acute non-varicose upper gastrointestinal tract were finally enrolled. The clinical data, laboratory tests and endoscopic results of the patients were recorded, and the data from the 30-day survival group and the non-survival group were compared and analyzed.Results:Significant differences were observed in age, mean arterial pressure, pulse rate, albumin levels, total protein levels, blood urea nitrogen levels, glucose, Glasgow-Blatchford score (GBS), Rockall, and AIMS65 scores between the survival and non-survival groups (all P <0.05). The B/A ratio in the non-survival group was significantly higher than that in the survival group [(24.9 ± 16.4) vs. (9.0 ± 8.6) mg/g, P<0.001]. Receiver operating characteristic (ROC) curve showed that the best cutoff value of B/A ratio for predicting 30-day death was 32.08 mg/g, with a sensitivity of 0.776 and specificity of 0.823. There was a significant difference in the 30-day Kaplan-Meier survival curve between patients with B/A ratio ≥32.08 mg/g and those with B/A ratio <32.08 mg/g (Log Rank 32.229, P<0.001). Multivariate logistic regression analysis revealed that the B/A ratio (≥32.08 mg/g) was associated with 30-day mortality ( OR=4.87, 95% CI: 1.94-6.85, P<0.001). Area under the ROC curve (AUC) for B/A ratio, GBS, Rockall and AIMS65 scores for predicting 30-day mortality were 0.855 (95% CI: 0.807-0.902), 0.849 (95% CI: 0.796-0.901), 0.657 (95% CI: 0.576-0.737), and 0.828 (95% CI: 0.774-0.883), respectively. Conclusions:The B/A ratio is a simple but potentially useful prognostic factor of mortality in the ANVUGIB patients.
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Objective:To observe the effect of Gongyanping Capsule on genital tract infected by ureaplasma urealyticum and fertility of mice, and to explore its mechanism.Methods:One hundred female ICR mice were divided into normal control group, model control group, azithromycin group, the low and high-dose group of Gongyanping Capsule according to random number table method. Except for the normal control group, the other groups were infected with ureaplasma urealyticum to establish the reproductive tract inflammation model. The azithromycin group was given 40 mg/kg of azithromycin, the low and high-dose groups were given 50 and 100 mg/kg of Gongyanping Capsule respectively, the normal control group and model control group were given equal volume of normal saline, once a day, for 4 consecutive weeks. The fertility status of each group was recorded. HE staining was used to observe the pathological changes of the vaginal tissues of the mice in each group, and the content of monocyte chemoattractant protein 1 (MCP-1), IL-4, IL-12, TNF-α myeloperoxidase (MPO) and GSH-Px of the mice in each group were determined; RT-PCR and Western blot were used to determine the vagina level of mRNA and protein expressions of TLR4 and NF-κB.Results:Compared with the model control group, the birth time and the number of dead mice in the azithromycin group and the low and high dose groups of Gongyanping Capsule decreased ( P<0.05), and the number of born mice increased ( P<0.05). The level of MCP-1, MPO, IL-4, IL-12, TNF-α decreased ( P<0.05), the level of GSH-Px increased ( P<0.05), the expression of TLR4 mRNA (1.25±0.33, 2.97±0.92, 2.32±0.72 vs. 3.69±1.32), NF-κB mRNA (1.48±0.42, 2.91±0.99, 2.13±0.70 vs. 3.83±1.41) decreased ( P<0.05), the expression of TLR4 (0.63±0.13, 1.32 ± 0.34, 1.04 ± 0.33 vs. 1.63 ± 0.41), NF-κB (0.63 ± 0.14, 1.36 ± 0.32, 1.03 ± 0.30 vs. 1.94 ± 0.58) decreased ( P<0.05), and had a certain dose-dependence. Conclusion:Gongyanping Capsule has obvious therapeutic effect on genital tract mice infected by ureaplasma urealyticum, and can significantly improve the fertility of mice; the mechanism may be related to that Gongyanping Capsule could inhibit the vaginal TLR4/NF-κB pathway in mice.
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Tumor microenvironment (TME) is composed of abnormal tumor vasculature, extracellular matrix components, endothelial cells, pericytes, tumor associated fibroblasts, smooth muscle cells and immune cells, which is characterized by hypoxia, acidosis and high interstitial fluid pressure. Hypoxia and acidosis within the TME trigger an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing tumor growth, angiogenesis, and ultimately, resulting in metastasis. What's more, the components of TME including abnormal tumor vasculature, rich composition of the ECM, and abundant stroma cells impair tumoral distribution and penetration of the drugs. At the same time, this stromal microenvironment plays a vital role in creating an immunosuppressive environment.Over the past years, more and more researches focus on targeting and remolding TME to improve therapeutic effects against tumors. Herein, we reviewed current strategies developed to target and remodel TME, including modulating tumor hypoxia, tumor vasculature, tumor associated fibroblasts, extracellular matrix components, tumor associated macrophage phenotypes and dendritic cells. Also, potential problems and future directions are pointed out in this review.
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Objective:To investigate the effects of comprehensive geriatric assessment(CGA)and intervention on treatment outcomes of type 2 diabetes and concurrent emotional disorders in the elderly.Methods:108 type 2 diabetes cases with emotional disorders were enrolled from March 2020 to March 2021 in the First Affiliated Hospital of Zhengzhou University and randomly divided into the conventional treatment group and the CGA group(54 cases each). The control group was given standard drug treatment and psychological counseling, whereas the CGA group was additionally given individualized treatment based on CGA guidelines.After observation for 8 weeks, clinical effects in the two groups were examined.Changes in cognitive status, nutritional status, fall risk and results on other indicators in patients were comprehensively assessed and statistically analyzed.Results:Compared with pre-treatment data, 8 weeks of treatment for both the control group and the CGA group resulted in decreased FPG levels[control group(10.16±0.90)mmol/L, (8.70±2.98)mmol/L, t=2.58, P=0.011; CGA group: (9.94±0.82)mmol/L, (7.12±2.25)mmol/L, t=8.65, P=0.000], 2hPG levels[control group: (11.83±3.92)mmol/L, (10.53±2.70)mmol/L, t=2.01, P=0.047; CGA group: (10.64±2.99)mmol/L, (9.26±1.89)mmol/L, t=2.87, P=0.005], HbA 1C(%)[control group: (9.76±1.09)%, (8.66±2.64)%, t=2.83, P=0.006; CGA group: (9.38±2.92)%, (7.81±1.78)%, t=3.37, P=0.001], HAMD-24 scores[control group(25.69±4.70), (24.20±2.48), t=2.06, P=0.042; CGA group(24.03±4.00), (22.11±1.38), t=3.33, P=0.001], and HAMD-14 scores[control group(19.66±2.84), (18.41±2.34), t=2.50, P=0.014; CGA group(18.77±2.48), (17.39±2.36), t=2.96, P=0.004], respectively, with more marked changes in all measures in the CGA group than in the control group(all P<0.05). Conclusions:Early CGA can effectively improve blood glucose levels and relieve mood disorders in elderly type 2 diabetes with emotional disorders.