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Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.
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Humains , Analyse coût-bénéfice , Arrêter de fumer , Évaluation du Coût-Efficacité , Tumeurs du rhinopharynx , Varénicline , Chine , Tumeurs du rein , Préparations pharmaceutiquesRésumé
Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.
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Humains , Analyse coût-bénéfice , Arrêter de fumer , Évaluation du Coût-Efficacité , Tumeurs du rhinopharynx , Varénicline , Chine , Tumeurs du rein , Préparations pharmaceutiquesRésumé
@#Abstract: Objective To investigate the clinical features and risk factors for severe tsutsugamushi disease, so as to provide reference for diagnosis and differentiation of severe tsutsugamushi disease as soon as possible. Methods The clinical data of 178 cases of inpatients with tsutsugamushi disease admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from January 2016 to September 2021 were collected and analyzed according to their gender, age, underlying diseases, clinical characteristics at admission, laboratory examination results within 24 hours of admission and epidemiological history. The patients were divided into the severe group and the non-severe group according to the diagnostic criteria. The data of clinical characteristics, laboratory examination and prognosis of the two groups were compared. Multivariate logistic regression analysis was performed on the variables with statistical significance and the receiver operating characteristic curve (ROC) was drawn. Results A total of 178 patients were included in this study, with 37 in the severe group and 141 in the non-severe group. Compared with the non-severe group, the age of the severe group was older, the underlying diseases were more, the incidence of dyspnea and the levels of white blood cell, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, cystatin C, uric acid and serum creatinine were significantly increased, the levels of platelet and albumin were significantly decreased (all P<0.05). The dyspnea [odds ratio (OR value)=8.93, 95% confidence interval (CI): 1.200-66.424; P=0.032], total bilirubin (OR=1.091, 95%CI: 1.028-1.159; P=0.004) and serum creatinine (OR=1.052, 95%CI: 1.004-1.102; P=0.033) were independent risk factors for severe tsutsugamushi disease. The area under ROC curve of total bilirubin and serum creatinine were 0.777 and 0.764, respectively (both P<0.01), indicating high predictive value for severe tsutsugamushi disease. The optimal cut-off value for total bilirubin was 23.01 µmol/L, with a sensitivity of 54.10% and a specificity of 90.60%; the optimal cut-off value for creatinine was 126.45 µmol/L, with a sensitivity of 43.20% and a specificity of 100.00%. The case fatality rate of severe tsutsugamushi disease was 2.70%. Conclusions The patients with severe tsutsugamushi disease are older, and have more underlying diseases. Dyspnea, increased total bilirubin and elevated serum creatinine are independent risk factors for severe tsutsugamushi disease, which can help in the early identification of severe tsutsugamushi disease early.
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OBJECTIVE@#To investigate the genetic results of whole exome sequencing of bone marrow from new onset multiple myeloma (MM) patients to analyze the process of genetic clonal evolution in MM patients.@*METHODS@#Genomic DNA was extracted from bone marrow samples of 15 MM patients and the whole exomes sequencing was performed using next generation sequencing technology. Using own buccal cells as germline controls, combinated with clinical information, the mutation profile of genes from high-risk asymptomatic myeloma to symptomatic myeloma were analyzed, and genes that may be associated with the efficacy and side effects of bortezomib were screened.@*RESULTS@#Except for two patients in whom no peripheral neuropathy was observed after a short treatment period, other patients peripheral neuropathy developed of various degrees during treatment with bortezomib containing chemotherapy, and the vast majority of patients achieved remission after receiving this bortezomib-related chemotherapy regimen. All patients had comparable levels of the inherited mutations number, but the somatic mutations was correlated with disease evolution.@*CONCLUSION@#different gene "mutational spectra" exist in myeloma patients at different stages and are associated with progression through all stages of the disease.
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Humains , Myélome multiple/traitement médicamenteux , Bortézomib/usage thérapeutique , Moelle osseuse , , Muqueuse de la bouche , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutiqueRésumé
Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
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Animaux , Rats , Protéines proto-oncogènes c-akt/génétique , Phosphatidylinositol 3-kinases/génétique , Espèces réactives de l'oxygène , Protéine p53 suppresseur de tumeur/génétique , Transduction du signal , Foie , Vieillissement , Protéines du cycle cellulaire , Interleukine-6Résumé
Objective:To investigate the analgesic effect and safety of using an epidural analgesia pump versus an intravenous analgesia pump for uterine artery embolization in the treatment of uterine fibroids. Methods:Fifty patients with uterine fibroids undergoing uterine artery embolization admitted to The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2019 to December 2021 were included in this study. They were divided into an observation group and a control group ( n = 25/group). Patients in the observation group used an epidural analgesia pump for pain relief, while patients in the control group used an intravenous analgesia pump for pain relief. At 1, 6, 12, and 24 hours after surgery, pain severity was compared between the two groups using the Visual Analogue Scale. Comfort level was compared between the two groups using the Bruggemann Comfort scale. Before and after surgery, respiratory rate, heart rate, blood pressure, and adverse reactions were compared between the two groups. Results:At 1 hour after surgery, the Visual Analogue Scale score in the observation group was significantly lower than that in the control group [3.00 (2.00, 5.50) vs. 7.00 (6.00, 8.00), Z = -3.84, P < 0.05]. At 6, 12, and 24 hours after surgery, there was a significant difference in the Visual Analogue Scale score between the two groups (all P > 0.05). Within 24 hours after surgery, the use of opioid analgesics in the observation group was less than that in the control group [16.00% (4/25) vs. 88.00% (22/25), χ2 = 25.96, P < 0.001]. At 1 hour after surgery, the Bruggemann Comfort Scale score in the observation group was significantly higher than that in the control group [0.00 (0.00, 0.50) vs. 0.00 (0.00, 0.00), Z = 2.08, P < 0.05]. At 6, 12, and 24 hours after surgery, there was no significant difference in the Bruggemann Comfort Scale score between the two groups (all P > 0.05). After surgery, heart rate was significantly decreased in each group compared with before surgery (both P < 0.05). There were no significant differences in respiratory rate and mean arterial pressure between the two groups before and after surgery (both P > 0.05). There were no significant differences in the incidences of postoperative nausea, vomiting, and fever between the two groups (all P > 0.05). Conclusion:The epidural analgesia pump used for uterine artery embolization in the treatment of uterine fibroids has a better analgesic effect and provides more comfort and is safer than the intravenous analgesia pump. The former is worthy of clinical promotion.
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Objective:To analyze the epidemiological and clinical characteristics of patients with tsutsugamushi disease in Guangdong Province from 2016 to 2021, and to provide a reference for clinical diagnosis, treatment, scientific prevention and control of tsutsugamushi disease.Methods:A retrospective analysis was conducted to collect the information of patients with tsutsugamushi disease admitted to Guangzhou Eighth Hospital Affiliated to Guangzhou Medical University from 2016 to 2021, including the basic information, epidemiological characteristics, clinical manifestations, auxiliary examinations, complications, misdiagnosis at first diagnosis and treatment outcomes.Results:Among 155 patients with tsutsugamushi disease, there were 75 males (48.39%) and 80 females (51.61%), with an e age of (54.41 ± 13.78) years old, and 30 cases (19.35%) had other underlying diseases. The peak time of onset was from June to September. There were 97 local patients (62.58%) in Guangzhou, and 58 cases (37.42%) in other prefecture-level cities; 76.77% (119/155) had a history of field activities before the onset of the disease. 36.13% (56/155) were farmers. The most common clinical manifestations were fever (100.00%, 155/155), chills and/or shivering (77.42%, 120/155), headache and/or dizziness (74.19%, 115/155), fatigue (65.81%, 102/155), eschar or ulcer (92.90%, 144/155), and lymphadenopathy (49.68%, 77/155). The laboratory test results mainly showed a decrease in eosinophils (81.94%, 127/155), a decrease in hematocrit (78.71%, 122/155), a decrease in hemoglobin (52.26%, 81/155), a decrease in platelet count (50.97%, 79/155), a decrease in albumin (92.26%, 143/155), an increase in lactate dehydrogenase (90.32%, 140/155), an increase in adenosine deaminase (88.39%, 137/155), and an increase in alanine aminotransferase (85.16%, 132/155), elevated aspartate aminotransferase (85.16%, 132/155), and elevated procalcitonin (52.90%, 82/155); 30 cases (19.35%) were positive for the Weil-Felix Test. There were 95 cases (61.29%) with abnormal chest imaging results, and 34 cases (21.94%) with abnormal abdominal ultrasound or CT results. Common complications were toxic hepatitis, pulmonary infection, organ failure, and acute kidney injury, etc. The misdiagnosis rate of the initial diagnosis of this disease was 75.48% (117/155). Doxycycline and symptomatic and supportive therapy were given, 154 patients (99.35%) were cured or improved and discharged from hospital.Conclusions:Tsutsugamushi disease is prevalent in summer and autumn in Guangdong Province. Before the onset, most of the patients have a history of field activities. Farmers are susceptible people. Its clinical manifestations are diverse, and can affect multiple systems and organs. There are many complications, and doxycycline can be used for anti-infection treatment, with a high cure rate.
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@#Abstract: Objective To investigate the dynamic changes and clinical significance of specific antibodies in patients with coronavirus disease 2019 (COVID-19). Methods A retrospective study was conducted to collect 141 adult COVID-19 survivors who were followed up in the Eighth Hospital affiliated to Guangzhou Medical University from February 6, 2020, to March 24, 2021. The patients were divided into severe group (severe and critical) and non-severe group (light and ordinary) according to the diagnosis at discharge. The antibody changes of the two groups were compared and analyzed at 1 week, 2 weeks, 1 month, 3 months, 6 months and 1 year after discharge. Results After discharge from hospital, the positive rate of IgG in the severe group was 95.00% after 1 week and 100.00% in the following year, in the positive rate of IgG in the non-severe group was 59.50% after 1 week, 90.08% in 6 months and 76.03% in one year. The level of serum IgG in the severe group was significantly higher than that in non-severe group (Z=-2.441, P=0.015). One-year follow-up: the serum IgG in the severe group was significantly higher than that in the non-severe group (Z=-3.410, P=0.001). The serum IgM level of the severe group after one year follow-up was lower than that of the six months follow-up, the difference was statistically significant (Z=-2.259, P=0.024). The serum IgG and IgM level of the non-severe group after one year follow-up was lower than that of the six months follow-up, the difference was statistically significant (Z=-7.37, P<0.01; Z=3.850, P<0.01). Conclusion The level of serum protective antibody in COVID-19 patients remained high within 6 months after discharge, and remained stable within 1 year after discharge. The antibody titers in the severe group were significantly higher than those in the non-severe group and lasted for at least one year. COVID-19 survivors receive 1 year of natural immune protection, and patients with critical conditions receive immunity for longer periods of time.
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This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.
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Animaux , Rats , Diabète , Néphropathies diabétiques/traitement médicamenteux , Médicaments issus de plantes chinoises , Insulinorésistance , Podocytes , PyroptoseRésumé
Objective:To investigate the long-term effects of porcine small intestinal submucosa (SIS) biologic mesh in open Lichtenstein tension-free hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 76 patients with unilateral inguinal hernia who underwent open Lichtenstein tension-free hernia repair in 2 medical centers (52 cases in Tianjin People′s Hospital and 24 cases in China-Japan Friendship Hospital) from August 2013 to March 2014 were selected. Based on random number method, patients were allocated into two groups. Patients undergoing Lichtenstein tension-free hernia repair using Biodesign Surgisis mesh were allocated into control group, and patients undergoing Lichtenstein tension-free hernia repair using SIS biologic mesh were allocated into experiment group. Observa-tion indicators: (1) grouping situations of the enrolled patients; (2) postoperative long-term effects. Follow-up was conducted using telephone interview, text message or mail to detect hernia recurrence or death due to other reasons as the end-point event of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented by M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping situations of the enrolled patients: a total of 76 patients were selected for eligibility. There were 38 cases in the control group and the experiment group, respectively. The number of males and females, age, body mass index, cases with intraspinal anesthesia or local anesthesia (anesthesia method), cases with inguinal hernia on the left side or on the right side, cases classified as type Ⅰ, Ⅱ, Ⅲ, Ⅳ or Ⅴ of Gilbert classification, operation time of the control group were 35, 3, (56±15)years, (23.0±2.0)kg/m 2, 22, 16, 16, 22, 9, 16, 0, 11, 2 and (49±15)minutes, respectively. The above indicators of the experiment group were 34, 4, (54±13)years, (22.9±2.2)kg/m 2, 17, 21, 14, 24, 9, 21, 1, 7, 0, and (53±21)minutes, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.157, t=0.532, 0.367, χ2=1.317, 0.220, Z=-0.315, t=-0.765, P>0.05). (2) Post-operative long-term effects: 35 patients of the control group were followed up for (68.8±2.7)months, 4 cases of which died due to other reasons, 1 case had hernia recurrence, 1 case had chronic pain and no foreign body sensation and postoperative infection occurred. Thirty-one patients of the experiment group were followed up for (68.8±2.7)months, with no death or above complications. There was no significant difference in hernia recurrence or chronic pain between the two groups ( P>0.05). Conclusion:The long-term effects of biological mesh in open Lichtenstein tension-free hernia repair is satisfactory and there is no difference in the long-term effects between the domestic SIS biological mesh and Biodesign Surgisis mesh.
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Objective:To explore the clinical characteristics of imported malaria from Africa, and the correlation between blood lipids and disease severity.Methods:The clinical data of 172 imported malaria patients from Africa were collected from January 1, 2018 to January 31, 2021 in Guangzhou Eighth People′s Hospital, Guangzhou Medical University. The general conditions, clinical symptoms, laboratory tests, treatment and prognosis of the patients were analyzed retrospectively. The independent samples t-test, Mann-Whitney U test and binary multivariate logistic regression analysis were used for statistical analysis when appropriate. Results:A total of 172 patients were divided into 39 severe cases and 133 non-severe cases in this study. The main infection species was Plasmodium falciparum, with a total of 153 cases (89.0%), and the severe cases were all falciparum malarias. Compared with the non-severe group, the white blood cell count and triacylglycerol level were increased in the severe group.The differences were both statistically significant ( Z=2.397 and 4.368, respectively; both P<0.05). The hemoglobin, hematocrit, platelet count, high-density lipoprotein cholesterol, apolipoprotein A (ApoA)Ⅰ and ApoAⅠ/apolipoprotein B (ApoB) were significantly decreased in the severe group. The differences were all statistically significant ( Z=-4.473, -4.464, -4.750, -4.826, -5.488 and -4.419, respectively; all P<0.01). The total cholesterol and low-density lipoprotein cholesterol were also reduced in the severe group. The differences were both statistically significant ( t=3.817 and 5.285, respectively; both P<0.01). The area under receiver operator characteristic curve of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, ApoAⅠ, and ApoAⅠ/ApoB were 0.754, 0.727, 0.730, 0.789 and 0.733, respectively (all P<0.01). When the Youden index was at its maximum, the best cut-off value of ApoAⅠ was 0.535 g/L with sensitivity of the prediction for severe malaria of 79.5% and the specificity of 68.4%. ApoAⅠ had independent predictive value for severe malaria (odds ratio ( OR)=0.013, 95% confidence interval ( CI) 0.002 to 0.086, P<0.01), and stratified according to the best cut-off value, the risk of severe malaria when ApoA Ⅰ<0.535 g/L was 8.396 times of ApoA Ⅰ≥0.535 g/L ( OR=8.396, 95% CI 3.557 to 19.820, P<0.01). The case fatality rate of severe malaria was 2.6%(1/39). Conclusions:The imported malaria patients from Africa are mainly infected with Plasmodium falciparum and the case fatality rate of severe malaria is high. The high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, ApoAⅠ, ApoAⅠ/ApoB of blood lipids show higher predictive value for severe malaria, among which, ApoAⅠ has independent predictive value for severe malaria. Changes in blood lipids will help to identify severe malaria as early as possible, improve the cure rate, and reduce the risk of death.
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As the body ages, the immune system will undergo a series of changes, which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils, monocytes/macrophages, myeloid-derived suppressor cells, dendritic cells, natural killer cells, etc., and the underlying mechanisms involve the regulation of cell number, phagocytosis, chemotaxis, adhesion, the function of toll-like receptor (TLR), antigen presentation, macrophage polarization, cytotoxicity, migration, etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes, and the underlying mechanisms involve the regulation of cell development, proliferation, differentiation, cell number, telomerase activity, self-reactive antibodies, etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years, scholars have found some classical prescriptions and their active components (such as Dushentang and total saponins in Panax ginseng leaves, and Shengmaiyin and anwulignan and total saponins in P. ginseng stems and leaves) can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition, the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration, Dahuang Zhechongwan, can delay D-galactose-induced renal aging in mice, and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore, exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.
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Caveolin-1 (Cav-1), a major structural protein of caveolae, is implicated in the vesicular uptake processes of transcytosis and cell signaling. However, its role in modulating protein glycosylation and tumor metastasis remains to be further elucidated. In the present study, it was shown that Cav-1 promotes the expression of O-GlcNAcylation and O-GlcNAc transferase (OGT), and triggers the invasion and metastasis of hepatocellular carcinoma (HCC) cells. The results of RT-qPCR, Western blot and dual lucif-erase reporter assay showed that Cav-1 negatively regulated the expression of transcription factor RUNX2 in HCC. Subsequently, this results in attenuate RUNX2-induced transcription of miR24. miR24 suppresses mouse HCC cells invasion and metastasis via directly targeting Ogt mRNA 3′UTR. This research provides evidence of Cav-1-mediated OGT expression and O-GlcNAc (O-linked N-acetylglucosamine) elevation. These data give insight into a novel mechanism of HCC occurrence and development.
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OBJECTIVE:To study FDA data standards program in the United States ,and to provide reference for constructing medicine data standards in China. METHODS :By analyzing the governance organization and policy system of FDA data standards program in the United States ,the experience were summarized for data standards development mode and development procedure , and relevant suggestions were put forward for medicine data standards construction in China. RESULTS & CONCLUSIONS :The organization of FDA data standards program is led by the Chief Scientist Office of FDA ,coordinated by the Data Standards Advisory Board ,specifically responsible by the Data Standards Program Board under the center for Drug Evaluation and Research , and participated by other regulatory centers and offices under FDA. FDA data standards program is composed of 4 subsystems as data standards strategy ,data standards program action plan ,data standards catalog and data standard communication plan. According to the federal laws and regulations of the United States ,the demand of FDA and pharmaceutical industry for data standards and the importance of data standards ,the strategic objectives of data standards development are proposed ,and the strategic objectives are refined into specific projects through the data standards program action plan. These programs strictly follow the“data standards development process ”and gradually advance quarterly ,and new data standards will be included in the Data Standards Catalog . At the same time ,FDA strengthen the cooperation and communication with internal and external stakeholders through the data standards program communication plan. It is suggested that China should learn from the experience of FDA data standards program construction ,establish a medical and health data standards program management mode ,strengthen the participation of internal and external stakeholders ,establish data standards committee ,formulate data standards catalog ,and provide clear and unified data standards for the pharmaceutical industry ,so as to promote the construction of medicine data standards in China.
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@#ObjectiveTo investigate the risk factors for death within 30 days in patients with liver cirrhosis and bacterial ascites, and to establish a predictive model of death within 30 days. MethodsA retrospective analysis was performed for the clinical data of 86 patients with liver cirrhosis and bacterial ascites who were admitted to Beijing Ditan Hospital, Capital Medical University, from January 2012 to April 2018. The patients were followed up for 30 days, and according to their prognosis, they were divided into survival group with 73 patients and death group with 13 patients. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the influencing factors for death within 30 days in patients with liver cirrhosis and bacterial ascites, and a predictive model was established based on these influencing factors. The area under the receiver operating characteristic curve was used to evaluate the predictive value of each independent influencing factor and the predictive model. ResultsThe multivariate logistic regression analysis showed that there were significant differences between the survival group and the death group in ascites albumin (odds ratio [OR]=0.615, 95% confidence interval [CI]: 0.424-0.893, P=0.011), neutrophil-to-lymphocyte ratio (NLR) (OR=1.170, 95%CI: 1.011-1.354, P=0.035), and Model for End-Stage Liver Disease (MELD) score (OR=1.341, 95% CI: 1.111-1.618, P=0.002). A scoring model was established based on the results of the multivariate analysis to predict death within 30 days in patients with liver cirrhosis and bacterial ascites, and based on this model, the patients were divided into high-risk group with death within 30 days (score ≥2 points) and low-risk group with death within 30 days (score <2 points). There was a significant difference in mortality rate with 30 days between the two groups (60.0% vs 5.6%, P<0.001). ConclusionAscites albumin ≤3.5 g/L, NLR ≥6.5, and MELD score ≥20 are independent risk factors for death within 30 days in patients with liver cirrhosis and bacterial ascites. The predictive model established on this basis can effectively evaluate the population at high risk of death within 30 days.
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Objective@#To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD.@*Methods@#Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance.@*Results@#Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant (P< 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant (P< 0.05). NAFLD group (P= 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower (P< 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant (P= 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower (P< 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant (P< 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels (r< 0,P< 0.05), and positively correlated with high-density lipoprotein levels (r> 0,P< 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha (r= -0.211,P= 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels (r> 0,P< 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level (r= 0.245,P= 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels (r > 0,P< 0.05). Megamonas was negatively correlated with high-density lipoprotein levels (r= -0.231,P= 0.027).@*Conclusion@#A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.
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Objective To explore the value of low-dose CT in the diagnosis of congenital heart disease(CHD)with tracheal stenosis (CTS)in infants.Methods Data of low-dose CT and echocardiography in 18 cases of CHD with CTS were analyzed retrospectively, and compared with surgical findings.Results 18 cases of CST were comfirmed by surgical operation.The diagnostic accuracy of low-dose CT was 100%,and there was no statistical difference in the assessment of the range and degree in tracheal stenosis(P=0.76>0.05, P=0.767>0.05).42 cardiac anomalies were comfirmed by operation.The diagnostic accuracies of low-dose CT and echocardiography were 88.1% and 90.5% respectively,which was no statistical difference(P=0.825>0.05).15 cases of CTS(15/18,83.33%)were caused by the compression of the vessels,in which there were 9 cases by pulmonary artery sling,3 cases by vascular ring,3 cases by double aortic arches.Conclusion Low-dose CT can accurately diagnose CHD with CTS and provide important information for clinical practice.
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Objective To evaluate the value of MRI in diagnosis of brachial plexus injury in infants.Methods MRI manifestations and electromyography(EMG) data of 14 cases were analyzed retrospectively.Kappa statistic was used to analyze the consistency between the two methods.Results Pure preganglionic injuries were found in 5 cases,preganglionic and postganglionic combined injuries occurred in 9 cases.MRI features of preganglionic injuries include:absence of roots in spinal canal (7 cases),nerve root enlargement (1 case),nerve sleeve dilation (3 cases),pseudomeningoceles (5 cases) and the dura thickening (3 cases).MRI features of postganglionic injuries include:trunk thickening with hyperintensity in STIR images(14 cases),adjacent structure disorder and edema (1 cases).The consistency of MRI and EMG was good (κ=0.752,P<0.05).Conclusion MRI is an efficient method for demonstrating preganglionic and postganglionic injuries,and can provide reliable information for early diagnosis and treatment for brachial plexus injury in infants.
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Objective To evaluate the application value of early lung ultrasound score(LUS)in the eval-uation of severity and prognosis of severe pneumonia and investigate its correlations with oxygenation index(OI), alveolar-arterial oxygen difference(A-aDO2),lymphocyte count(LYM),positive end-expiratory pressure(PEEP), acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,and clinical pulmonary infection score (CPIS). Methods Thirty severe pneumonia patients admitted to intensive care unit(ICU)of Guangzhou Eighth People's Hospital from May 2015 to July 2017 were enrolled,including 14 cases with low PEEP and 16 cases with high PEEP. Among them,17 patients were diagnosed with non-viral pneumonia and 13 ones with viral pneumonia;15 of them survived,and 15 died. The clinical data and cores of all patients were recorded by one observer,including baseline date,OI,A-aDO2,LYM,PEEP,and APACHEⅡ and CPIS score. The other observer was specifically responsible for pulmonary ultrasonography and LUS. The correlation between LUS and OI,A-aDO2,LYM,PEEP, as well as APACHEⅡand CPIS scores was analyzed by bivariate correlation analysis. Receiver operator character-istic curves(ROC)were plotted,and the prediction value,sensitivity and specificity of high PEEP and mortality by LUS were calculated respectively. Results LUS had a negative correlation with OI(r =-0.755,P = 0.000) and LYM(r =-0.518,P = 0.03),and a good positive correlation with A-aDO2(r = 0.642,P = 0.000),PEEP (r = 0.583,P = 0.001),APACHEⅡ(r = 0.461,P = 0.010)and CPIS(r = 0.595,P = 0.001)was respectively found. LUS in the survival group was significantly lower than the death group(15.00 ± 5.90 vs. 22.27 ± 4.68,P<0.01),low PEEP group was obviously lower than high PEEP group(14.23 ± 5.40 vs. 22.00 ± 4.98,P < 0.01), and there was no significant difference between non-viral pneumonia group and viral pneumonia group(18.59 ± 6.49 vs. 18.69 ± 6.56,P > 0.05). The area under ROC cure(AUC)was calculated:the predictive value for high PEEP by LUS was 19,with the sensitivity of 77% and specificity of 92%,and the patients with LUS > 17 had a high mortality,with the sensitivity for predicting death of 87% and specificity of 67%. Conclusion Bedside lung ultrasound can easily evaluate the changes in pulmonary ventilation area ,and early LUS has important clinical application value in assessing the severity and prognosis of severe pneumonia patients.
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PURPOSE: Developing a risk prediction model for invasive fungal disease based on an analysis of the disease-related risk factors in critically ill patients in the intensive care unit (ICU) to diagnose the invasive fungal disease in the early stages and determine the time of initiating early antifungal treatment. METHODS: Data were collected retrospectively from 141 critically ill adult patients with at least 4 days of general ICU stay at Sun Yat-sen Memorial Hospital, Sun Yat-sen University during the period from February 2015 to February 2016. Logistic regression was used to develop the risk prediction model. Discriminative power was evaluated by the area under the receiver operating characteristics (ROC) curve (AUC). RESULTS: Sequential organ failure assessment (SOFA) score, antibiotic treatment period, and positive culture of Candida albicans other than normally sterile sites are the three predictors of invasive fungal disease in critically ill patients in the ICU. The model performs well with an ROC-AUC of .73. CONCLUSION: The risk prediction model performs well to discriminate between critically ill patients with or without invasive fungal disease. Physicians could use this prediction model for early diagnosis of invasive fungal disease and determination of the time to start early antifungal treatment of critically ill patients in the ICU.