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Objective:To explore the value of serum procalcitonin (PCT) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on predicting prognosis of elderly patients with sepsis.Methods:A retrospective cohort study, patients with sepsis who admitted to the department of emergency and the department of geriatric medicine of Peking University Third Hospital from March 2020 to June 2021 were enrolled. Patients' demographics, routine laboratory examinations, APACHE Ⅱ score that within 24 hours of admission were obtained from their electronic medical records. The prognosis during the hospitalization and one year after discharge were collected, retrospectively. Univariate and multivariate analysis of prognostic factors were performed. And Kaplan-Meier survival curves were used to examine overall survival.Results:A total of 116 elderly patients met inclusion criteria, 55 were alive and 61 were died. On univariate analysis, clinical variables such as lactic acid [Lac, hazard ratio ( HR) = 1.16, 95% confidence interval (95% CI) was 1.07-1.26, P < 0.001], PCT ( HR = 1.02, 95% CI was 1.01-1.04, P < 0.001), alanine aminotransferase (ALT, HR = 1.00, 95% CI was 1.00-1.00, P = 0.143), aspartate aminotransferase (AST, HR = 1.00, 95% CI was 1.00-1.01, P = 0.014), lactate dehydrogenase (LDH, HR = 1.00, 95% CI was 1.00-1.00, P < 0.001), hydroxybutyrate dehydrogenase (HBDH, HR = 1.00, 95% CI was 1.00-1.00, P = 0.001), creatine kinase (CK, HR = 1.00, 95% CI was 1.00-1.00, P = 0.002), MB isoenzyme of creatine kinase (CK-MB, HR = 1.01, 95% CI was 1.01-1.02, P < 0.001), Na ( HR = 1.02, 95% CI was 0.99-1.05, P = 0.183), blood urea nitrogen (BUN, HR = 1.02, 95% CI was 0.99-1.05, P = 0.139), fibrinogen (FIB, HR = 0.85, 95% CI was 0.71-1.02, P = 0.078), neutrophil ratio (NEU%, HR = 0.99, 95% CI was 0.97-1.00, P = 0.114), platelet count (PLT, HR = 1.00, 95% CI was 0.99-1.00, P = 0.108) and total bile acid (TBA, HR = 1.01, 95% CI was 1.00-1.02, P = 0.096) shown to be associated with poor prognosis. On multivariable analysis, level of PCT was an important factor influencing the outcome of sepsis ( HR = 1.03, 95% CI was 1.01-1.05, P = 0.002). Kaplan-Meier survival curve showed that there was no significant difference with respect to the overall survival between the two groups, with patients of PCT ≤ 0.25 μg/L and PCT > 0.25 μg/L ( P = 0.220). It also showed that the overall survival rate in patients with high APACHE Ⅱ score (> 27 points) was significantly lower than that in patients with low APACHE Ⅱ score (≤ 27 points, P = 0.015). Conclusion:Serum PCT level is valuable prognostic factors of elderly patients with sepsis, and higher APACHE Ⅱ score (> 27 points) indicates a poor prognosis.
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Objective:To analyze the clinical features of patients with severe dengue (SD) in Guangdong Province, and to improve the understanding of the diagnosis and treatment of SD in China.Methods:The clinical data, laboratory examination and etiological test results of 257 SD cases from 29 dengue fever designated hospitals in Guangdong Province from January 1, 2013 to December 31, 2019 were respectively collected. The relevant indicators of the criteria for severe organ involvement were quantified. Logistic regression analysis was performed to analyze the risk factors for the development of multiple organ failure in SD patients.Results:Among the 257 SD patients, age was (64.1±20.1) years old, with 65.4%(168/257) of them ≥60 years old, 142 were male and 115 were female. One hundred and fifty-two (59.1%) patients had underlying conditions, including 115(44.7%) patients with hypertension. The clinical manifestations were mainly fever (98.4%(253/257)), fatigue (70.0%(180/257)), cough or expectoration (44.4%(114/257)), lethargy or irritability (39.3%(101/257)), vomiting (30.4%(78/257)), abdominal pain or tenderness (20.6%(53/257)), hepatomegaly (2.3%(6/257)), bleeding tendency (59.5%(153/257)), and pleural effusion or ascites (43.6%(112/257)). Platelet count levels were decreased in 90.9%(231/254) of the cases, and 97.1%(234/241) of patients had normal or decreased hematocrit. The most common of severe manifestations were severe organ involvement (61.1%(157/257)), followed by severe bleeding (37.0%(95/257)) and severe plasma leakage (30.0%(77/257)). Severe organ involvements were more common in the kidney (27.6%(71/257)) and heart (26.8%(69/257)). Multivariate logistic regression analysis showed that age (odds ratio ( OR)=1.051, 95% confidence interval ( CI) 1.004 to 1.100, P=0.035), hypertension ( OR=5.224, 95% CI 1.272 to 21.462, P=0.022), elevated aspartate aminotransferase (AST) level ( OR=1.002, 95% CI 1.001 to 1.003, P=0.001), blood urea nitrogen (BUN) ( OR=1.050, 95% CI 1.005 to 1.098, P=0.030), and international normalized ratio (INR) ( OR=4.604, 95% CI 1.601 to 13.238, P=0.005) were risk factors for the development of multiple organ failure in SD patients. The detection results of serum samples form 113 SD patients in acute phase showed that dengue virus (DENV)-1 accounted for 89.4%(101/113), DENV-2 accounted for 9.7%(11/113), and DENV-3 accounted for 0.9% (1/113). Conclusions:Elderly and those with co-existing conditions such as hypertension in SD patients in Guangdong Province are more common. Severe organ involvement such as kidney and heart is the main cause of SD. DENV-1 infection is predominant. Significant elevated levels of AST, BUN and INR may be related to a poor prognosis.
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Objective:To compare the levels of cytokines in patients with dengue fever (DF) and severe dengue (SD) at different time points during the course of disease, to seek the cytokines that can be used as early warning signs of SD, and to explore the relationship between the immune response and the pathogenesis of SD.Methods:Plasma samples at different time points were collected from 60 hospitalized patients including 48 mild cases and 12 severe cases in Guangzhou Eighth People′s Hospital during June to December, 2014. Levels of 19 cytokines including TNF-α, IL-6, IL-8, IL-10, IL-15, IL-17A, IFN-α2, IP-10, MCP-1, RANTES, GRO-α, PDGF-AA, PDGF-AB/BB, MIF, VEGF, sVCAM-1, sICAM-1, sFas and sFasL were determined by a multiplex Luminex system.The viral loads were determined by using fluorescence quantitative RT-PCR and the correlation between viral loads and cytokine level were analyzed.Results:The levels of TNF-α, IL-6, IL-8, IL-10, IL-15, IFN-α2, IP-10, MCP-1 and sVCAM-1 increased in dengue patients, while RANTES, GRO-α and PDGF decreased.The levels of IL-17A, MIF, VEGF, sICAM-1, sFas and sFasL did not change. The levels of TNF-α, IL-6, IFN-α2, IP-10 and sVCAM-1 in SD patients were significantly higher than those in DF patients at the early stage (Day 2-5 after disease onset), and the differences were statistically significant. On day 6-10, the levels of TNF-α, IL-6, IL-8, IL-10, IL-15, PDGF, RANTES, IFN-α2, IP-10 and sVCAM-1 were significantly different between DF and SD patients. The results of correlation analysis showed that the level of IL-15 was moderately correlated with viral load, while other cytokines was only weakly correlated or not.Conclusions:TNF-α, IL-6, IFN-α2, IP-10 and sVCAM-1 can be used as early warning signs of SD. The level of cytokines is related to the severity of dengue fever.
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Objective:To investigate the serotype distribution and phylogenetic analysis of virus complete genome from indigenous dengue patients in Guangzhou in 2019 and provide evidence for the development of prevention and treatment strategies.Methods:Dengue virus serotypes of indigenous dengue cases in 2019 were detected using serotype specific fluorescent PCR kits. Complete genome in the culture was performed on Illumina platform. Phylogenetic analysis was conducted on complete genomes extracted from ViPR and the isolates from this study with MEGA7.0 software.Results:In 2019, three prevalent serotypes of dengue virus were found in Guangzhou, among which serotype 1 accounted for 80.35%, serotype 2 accounted for 12.97% and serotype 3 accounted for 6.68%. There were no significant differences in gender, age and severity among three serotypes. Phylogenetic analysis of virus complete genome showed that serotype 1 belonged to genotypeⅠand had two origins, which was close to the Cambodian strain; serotype 2 belonged to genotype cosmopolitan, which was close to the epidemic strain in Southeast Asia; serotype 3 belonged to genotypeⅢ, which was in the same branch as the Indian strain.Conclusions:The dengue epidemic was caused by dengue virus serotypes 1, 2 and 3 in Guangzhou in 2019. Each serotype belonged to a genotype.
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Objective:To analyze the epidemiological and clinical characteristics of hospitalized patients with dengue fever in Guangdong Province in 2019, so as to provide reference for clinical diagnosis and treatment of dengue fever.Methods:The general data, laboratory examination data, clinical manifestations and prognosis data of 480 inpatients with dengue fever admitted to Eight People′s Hospital Affiliated to Guangzhou Medical University between January 4 and October 31, 2019 were analyzed retrospectively. The clinical and onset characteristics of patients with dengue fever were described.Results:Among 480 dengue patients, 442(92.1%) were dengue fever, 38(7.9%) were severe dengue, and 136(28.3%) had underlying diseases. The peak age of onset was mainly in young adults aged 20 to 49 years old, accounting for 66.0%(317/480) in total. The seasonal peak was mainly in August to October. There were 399(83.1%) local cases and 61(12.7%) imported cases. The most common clinical manifestations were fever (98.1%, 471/480), chills (72.9%, 350/480), headache (58.5%, 281/480) and bone/joint/muscle pain (67.1%, 322/480), followed by digestive tract symptoms and respiratory tract symptoms. Among 446 serum samples, 358 (80.3%) were dengue virus (DENV)-1, 54 (12.1%) were DENV-2, 34 (7.6%) were DENV-3. The main laboratory tests of the patients were leucopenia (65.8%, 316/480), low hematocrit (30.2%, 145/480), thrombocytopenia (48.3%, 232/480), neutropenia (44.8%, 215/480), elevated alanine aminotransferase (ALT) (37.7%, 181/480) and aspartate aminotransferase (AST) (59.4%, 285/480). Treatment mainly adopted symptomatic support treatment and active prevention of complications. The length of stay was (5.8±3.1) days (range 1.0-38.0 days). A total of 461(96.0%) patients were cured or improved.Conclusions:In 2019, the majority of dengue fever patients in Guangdong Province are young adults aged 20 to 49 years old, and the proportion of severe patients is high, with DENV-1 infection as the main type. After symptomatic support treatment and active prevention of complications, most of the dengue fever patients have a good prognosis.
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Objective:To investigate the cardiac presentations and the possible influencing factors of severe and critical coronavirus disease 2019 (COVID-19).Methods:A retrospective study was conducted. Patients with severe and critical COVID-19 admitted to the Eighth People's Hospital of Guangzhou from January 21st to February 24th 2020 were enrolled. According to the clinical classification, the patients were divided into severe group and critical group. The myocardial injury markers, such as lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK), cardiac troponin I (cTnI), myoglobin (MYO), MB isoenzyme of creatine kinase (CK-MB), B-type natriuretic peptide (BNP) and electrocardiogram (ECG) changes were compared between the two groups.Results:A total of 55 COVID-19 patients were selected, including 15 critical cases and 40 severe cases. The patients with severe and critical COVID-19 were male-dominated (61.8%), the average age was (61.2±13.0) years old, 83.6% (46 cases) of them had contact history of Hubei, 38.2% (21 cases) of them were complicated with hypertension. There was no significant difference in baseline data between the critical group and the severe group. Myocardial injury markers of critical and severe COVID-19 patients were increased in different proportion, LDH increased in most patients (20 severe cases and 7 critical cases), followed by AST (16 severe cases and 5 critical cases). There was significant difference in the number of patients with elevated CK between severe group and critical group (cases: 1 vs. 4, P = 0.027). Abnormal ECG was found in 39 of 42 patients with ECG examination. Nonspecific change of T wave was the most common. Before and after treatment, 9 of 15 patients with changes of ECG and myocardial injury markers had oxygenation index less than 100 mmHg (1 mmHg = 0.133 kPa), and the prominent changes of ECG were heart rate increasing and ST-T change. Conclusions:The increase of myocardial injury markers and abnormal ECG were not specific to the myocardial injury of severe and critical COVID-19 patients. At the same time, the dynamic changes of myocardial injury markers and ECG could reflect the situation of myocardial damage.
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Objective:To analyze the clinical characteristics of patients with different types of coronavirus disease 2019 (COVID-19).Methods:A total of 272 eligible COVID-19 patients who were admitted to Guangzhou Eighth People′s Hospital, Guangzhou Medical University from January 22 to February 15, 2020 were retrospectively enrolled. General characteristics, the first laboratory examination and imaging data of these patients were collected. According to the clinical classification, there were 236 cases in non-severe group (mild+ common type) and 36 cases in severe group (severe+ critical type). Comparisons between groups were performed by t test, chi-square test or rank-sum test when appropriate. Results:There were 23 males and 13 females in the severe group, 103 males and 133 females in the non-severe group, and the difference was statistically significant ( χ2=5.149, P=0.023). The age of severe group was (60.5±11.2) years, which was higher than that of non-severe group (46.8±15.7) years. The difference was statistically significant ( t=6.43, P<0.01). The lymphocyte (LYM) count, platelet (PLT) count and arterial partial pressure of oxygen (PaO 2) in the severe group were 0.90(0.55, 1.10)×10 9/L, 170.00(143.50, 198.00)×10 9/L and 73.50(69.70, 83.00) mmHg(1 mmHg=0.133 kPa), respectively, which were all lower than those in the non-severe group (1.42(1.09, 1.95)×10 9/L, 187.00(148.00, 230.00)×10 9/L and 96.00(83.20, 108.00) mmHg, respectively). The differences were all statistically significant ( Z=5.59, 2.00 and 5.00, respectively, all P<0.05). The levels of creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C reaction protein (CRP) and procalcitonin (PCT) in the severe group were 123.00(79.00, 212.00) U/L, 32.10(27.00, 47.40) U/L, 305.50(216.00, 396.00) U/L, 37.02(23.92, 63.66) mg/L and 0.09(0.05, 0.19) μg/L, respectively, which were all higher than those in the non-severe group (68.00(48.00, 103.00) U/L, 20.10(16.70, 26.20) U/L, 179.00(150.00, 222.00) U/L, 26.55(18.11, 36.96) mg/L and 0.04(0.03, 0.06) μg/L respectively), and the differences were all statistically significant ( Z=3.89, 5.60, 5.12, 2.85 and 5.43, respectively, all P<0.01). No significant differences were observed in white blood cell count, creatine kinase isoenzyme and blood lactate between the two groups ( Z=1.53, 0.41 and 1.00, respectively, all P>0.05). Conclusion:Gender, age, LYM count, PLT count, PaO 2, CK, AST, LDH, CRP and PCT could be used to provide reference for clinical classification of COVID-19 patients.
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Objective:To investigate the clinical characteristics and CT imaging features of patients with different clinical types of coronavirus disease 2019 (COVID-19), so as to provide a reference for the treatment and evaluation of COVID-19.Methods:The clinical data of 278 patients with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20th to February 10th in 2020 were collected. The patients were divided into mild, ordinary, severe and critical types. The differences of clinical symptoms and signs, laboratory examination indexes and CT image features of lung in different clinical types were analyzed and compared, and the relationship between clinical and imaging features and clinical types of diseases were analyzed.Results:Among the 278 patients with COVID-19, 130 were male (46.8%) and 148 were female (53.2%), of whom 88.8% (247/278) were 20 to 69 years old. 238 (85.6%) patients combined one or more basic diseases. The source of cases was mainly imported cases ( n = 201, 72.3%), of whom 89 cases were imported from Wuhan, accounting for 44.3% of all imported cases. With the aggravation of the disease, the male composition ratio, age and the number of basic diseases of patients gradually increased, and the incidences of fever, dry cough, chilly or chills, and fatigue in severe and critical patients were significantly higher than those in the mild and ordinary ones. The white blood cell count (WBC), neutrophil counts (NEU) and proportions (NEU%) of the severe and critical patients were higher than those of the mild and ordinary patients [WBC (×10 9/L): 5.7±3.1, 6.5±2.4 vs. 5.4±1.7, 4.9±1.6; NEU (×10 9/L): 4.4±3.1, 4.9±2.5 vs. 2.8±1.2, 2.9±1.3; NEU%: 0.72±0.13, 0.73±0.14 vs. 0.51±0.12, 0.59±0.11; all P < 0.01], while the lymphocyte count (LYM) and ratio (LYM%), platelet count (PLT) were lower than those in the mild and ordinary patients [LYM (×10 9/L): 1.0±0.4, 1.2±0.8 vs. 2.1±0.9, 1.5±0.6; LYM%: 0.21±0.11, 0.20±0.12 vs. 0.40±0.11, 0.32±0.11; PLT (×10 9/L): 177.1±47.8, 157.7±51.6 vs. 215.3±59.7, 191.8±64.3; all P < 0.05]. The level of albumin (Alb) was the lowest in the critical patients and the level of total bilirubin (TBil) was the highest, which was statistically significant as compared with the mild, ordinary and severe patients [Alb (g/L): 33.0±5.8 vs. 42.8±4.4, 39.6±5.1, 34.4±4.2; TBil (μmol/L): 20.1±12.8 vs. 12.0±8.7, 10.9±6.3, 12.2±8.3; both P < 0.01]. Lactate dehydration (LDH) and cardiac troponin I (cTnI) in the severe and critical patients were significantly higher than those in the mild and ordinary patients [LDH (μmol·s -1·L -1): 5.6±2.2, 5.0±2.9 vs. 2.8±0.9, 3.3±1.2; cTnI (μg/L): 0.010 (0.006, 0.012), 0.010 (0.006, 0.012) vs. 0.005 (0.003, 0.006), 0.005 (0.001, 0.008); both P < 0.05]. C-reactive protein (CRP) level of severe patients were higher than that in the mild, ordinary and critical patients [mg/L: 43.3 (33.2, 72.1) vs. 22.1 (16.2, 25.7), 29.7 (19.8, 43.1), 25.8 (23.0, 36.7), P < 0.01]. The level of procalcitonin (PCT) in the severe and critical patients was higher than that in the mild and ordinary patients [μg/L: 0.17 (0.12, 0.26), 0.13 (0.09, 0.24) vs. 0.06 (0.05, 0.08), 0.05 (0.04, 0.09), P < 0.01]. The typical CT imaging features were as follows: the ordinary type mainly showed the single or multiple ground glass shadows on the chest image; the severe type mainly showed the multiple ground glass shadows, infiltration shadows or solid transformation shadows. Compared with the ordinary patients, the lesions increase, and the scope of the lesion expanded to show double lungs. Critical type was mainly manifested as diffuse consolidation of both lungs with multiple patchy density increase shadows, multiple leafy patchy density increase shadows were seen on each leaf, most of them were ground glass-like density, and some were shown separately lung consolidation. Conclusions:Men, advanced aged, and combining multiple underlying diseases are high-risk populations of COVID-19, and they should pay close attention to the risk of progressing to severe or critical type. CT imaging features could be used as an important supplement when diagnosing severe and critical COVID-19.
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Objective@#To analyze the clinical features of death cases of dengue fever and the causes of their deaths.@*Methods@#The clinical data and death reports of nine death cases of dengue fever in Guangdong Province from June 23, 2014 to September 10, 2019 were retrospectively analyzed. All of nine cases were positive for serum dengue virus RNA as confirmed by reverse transcription polymerase chain reaction, and some of the virus strains were serotyped.@*Results@#The median age of the nine patients was 57.5 (range: 18-80) years. Among them, six patients were females; eight patients were local cases and one was imported case; all of nine cases occurred in September and October. The median time from onset to visit hospital and diagnosis was three and four days, respectively. Three of the nine patients had underlying diseases. All of nine cases had fever, including three with double-peak fever. Eight of the cases had three or more severe dengue fever warning indexes before admission. Three cases had severe bleeding upon admission, one case had shock, and six cases had organ failure. Three cases underwent invasive examination, including arterial puncture catheterization, endoscopic titanium clip hemostasis, and percutaneous transluminal coronary angiography. Two cases developed malignant arrhythmia and one had massive hemorrhage of subcutaneous soft tissue after operation. The death cases included four cases of cardiogenic shock and fatal arrhythmia, three cases of encephalitis and encephalopathy, one case of refractory shock, and one case of acute liver failure. Among the six cases that underwent serological typing, four were identified as dengue virus type 1 (DEN-1) and two were DEN-2.@*Conclusions@#Severe organ failure is the major cause of dengue fever-related death, especially fulminant myocarditis, and DEN-1 is most common. Early diagnosis and treatment, and avoidance of invasive procedures can effectively reduce the mortality rate of the severe dengue fever patients.
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Objective To analyze the clinical features of death cases of dengue fever and the causes of their deaths.Methods The clinical data and death reports of nine death cases of dengue fever in Guangdong Province from June 23,2014 to September 10,2019 were retrospectively analyzed.All of nine cases were positive for serum dengue virus RNA as confirmed by reverse transcription polymerase chain reaction,and some of the virus strains were serotyped.Results The median age of the nine patients was 57.5(range: 18-80)years.Among them,six patients were females; eight patients were local cases and one was imported case; all of nine cases occurred in September and October.The median time from onset to visit hospital and diagnosis was three and four days,respectively.Three of the nine patients had underlying diseases.All of nine cases had fever,including three with double-peak fever.Eight of the cases had three or more severe dengue fever warning indexes before admission.Three cases had severe bleeding upon admission,one case had shock,and six cases had organ failure.Three cases underwent invasive examination,including arterial puncture catheterization,endoscopic titanium clip hemostasis,and percutaneous transluminal coronary angiography.Two cases developed malignant arrhythmia and one had massive hemorrhage of subcutaneous soft tissue after operation.The death cases included four cases of cardiogenic shock and fatal arrhythmia,three cases of encephalitis and encephalopathy,one case of refractory shock,and one case of acute liver failure.Among the six cases that underwent serological typing,four were identified as dengue virus type 1(DEN-1)and two were DEN-2.Conclusions Severe organ failure is the major cause of dengue fever-related death,especially fulminant myocarditis,and DEN-1 is most common.Early diagnosis and treatment,and avoidance of invasive procedures can effectively reduce the mortality rate of the severe dengue fever patients.
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Objective To investigate the effects of ethyl acetate phase of Pleurotus ferulatus triterpenoid component (PFTP-E), oleanolic acid (OA) and paclitaxel (PTX) on growth inhibition and possible regulation mechanisms of colon cancer cells HCT116 and CT26. Methods Ultraviolet and infrared spectroscopy was used to analyze the component of PFTP-E. MTT assay was used to detect the proliferation of HCT116 and CT26 cells by PFTP-E, OA and PTX in vitro. Apoptosis was observed by Hoechst 33258 staining. Flow cytometry was used to detect apoptosis, cell cycle, mitochondrial membrane potential and intracellular ROS. Western Blot were used to detect the expressions of apoptosis-related proteins B cell lymphoma-2 (Bcl-2), BCL2 associated X protein (Bax), poly(adenosine diphosphate-ribose) polymerase (PARP), Caspase-3, Caspase-9, cell cycle related proteinB1 (Cyclin B1), endoplasmic reticulum stress-related proteins glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), eukaryotic initiation factor 2α(eIF2α), C/EBP-homologous protein (CHOP), and autophagy microtubule associated protein light chain 3A/B (LC3A/B). Results PFTP-E is mainly composed of steroids and triterpenoids. PFTP-E, OA and PTX can inhibit the proliferation of HCT116 and CT26 cells in a time- and dose-dependent manner, induce apoptosis, and block the cell cycle at G0/G1 and G2/M phases. PFTP-E can collapse mitochondrial membrane potential of HCT116 and CT26 cells and increase the content of intracellular reactive oxygen species, which is similar to the effect of PTX. PFTP-E and PTX can up-regulate CytC, Bax, GRP78, p-PERK, p-eIF2α and CHOP, down-regulate Bcl-2, significantly increase the content of cleaved PARP, Caspase3 and Caspase9, and induce endoplasmic reticulum stress response. OA can significantly increase the expression of LC3A/B in HCT116 cells and tend to induce autophagy and apoptosis. Conclusions PFTP-E and PTX have a similar effect on apoptosis, and that is related to mitochondrial injury pathway, cycle arrest, and endoplasmic reticulum stress response. The side effects of PFTP-E are significantly lower than PTX, which provides a meaningful reference for the screening and research of PFTP-E as an anticancer drug.
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Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.
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Objective@#To investigate the roles of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), retinoic acid-inducible geneⅠ-like receptors (RLRs) and nucleotide binding oligomerization domain-like receptors (NLRs) in the pathogenesis of dengue fever (DF) and the induction of immune responses to dengue virus.@*Methods@#Blood samples were collected from patients with DF at three different time points to isolate peripheral blood mononuclear cells (PBMCs) by density gradient centrifugation. Then PBMCs were used to extract ribonucleic acid (RNA). Expression of genes was detected by polymerase chain reaction (PCR) array.@*Results@#Expression of genes relating to PRRs signaling pathways in DF patients increased significantly in the early stage of the disease as compared with those in healthy controls, but decreased gradually during the recovery period. Expression of genes encoding TLR7 and TLR8 was enhanced at the early stage of DF. No significant changes in the expression of TLR3 and TLR9 genes were observed during the course of the disease. The genes encoding RIG-Ⅰ, MDA5 and LGP2 of RLRs family as well as NOD2 and OAS2 of NLRs family were all up-regulated.@*Conclusion@#Signaling pathways mediated by PRRs including TLR7/8, RIG-Ⅰ, MDA5 and so on play an important role in the pathogenesis of DF and the induction of immune responses to dengue virus.
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Objective@#To investigate the sensitivity and specificity of commercial nonstructural protein 1 (NS1) testing kits for Dengue fever diagnose, and provide the evidence for diagnostic criteria revision.@*Methods@#300 PCR or virus isolation positive blood samples for dengue virus were collected from sentinel hospitals for dengue surveillance in Guangzhou, Dongguang and Zhongshang from May 2015 to Nov. 2016. At the same time, 308 PCR negative samples for Dengue virus were collected as control group. The information of the sample was collected using questionnaires. These samples were tested using imported and domestic ELISA and the colloidal gold-labeled kits that were widely used for detecting dengue NS1. Sensitivity, specificity and coincidence were calculated and analyzed, and Z hongshan's result was regarded as the reslut of the third part.@*Results@#The positive group includes 133 males and 167 females, average ages are 47.2±13.3, 179, 110 and 11 of them is Dengue Ⅰ, Ⅱ and Ⅲ respectively. The negative group includes 154 males and 154 females, average ages are (40.1±11.6) years old. The sensitivity of domestic ELISA Kits (94.5%) is less than imported (99.5%), and the result has statistical significance (χ2=8.59, P=0.030), the specificity is 99.7% and 97.7% respectively; The sensitivity of imported and domestic the colloidal gold-labeled Kits is 97.5% and 96.5% respectively, both of specificities are 100%. The sensitivity and specificity of Dengue Ⅰ for NS1 test are more than 97.0%. The sensitivity of domestic ELISA and gold-labeled Kits is 90.0% and 95.0%, and the specificity is 96.8% and 100% respectively for Dengue Ⅱ test. The sensitivity of imported ELISA and gold-labeled Kits is 100% and 98.0%, and the specificity is 99.4% and 100% respectively for Dengue Ⅱ test. The result of the third party show the sensitivity and specificity of domestic ELISA and gold-labeled Kits are 90.0% and 98.0%, the differences has statistical significance (χ2=5.67, P=0.020).@*Conclusion@#NS1 testing can be used as early dengue fever diagnose for higher sensitivity and specificity.
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Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China displayed distinct clinical characteristics compared to patients in endemic countries.To standardize the diagnosis and treatment of dengue fever,the experts of the Society of Infectious Diseases,Society of Tropical Medicine and Parasitology of Chinese Medical Association,and the Society of Emergency Medicine,China Association of Chinese Medicine have reached this guideline based on guidelines for diagnosis,treatment,prevention and control of dengue (World Health Organization,2009);guidelines for diagnosis and treatment of dengue (National Health and Family Planning Commission of the People's Republic of China,2014,Edition 2),health industry standard of the People's Republic of China "diagnosis for dengue fever (WS216-2018)" and systemic reports on dengue.The guideline includes 8 aspects:introduction,terminology,epidemiology and prevention,etiology and pathogenesis,clinical features,diagnosis,treatment and problems to be solved.
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Objective To investigate the cognitive dysfunction of inpatients in geriatric department general hospital and to analyze the influencing factors.Methods A total of 205 patients hospitalized in Peking University Third Hospital were evaluated by mini-mental state examination (MMSE).All patients were divided into cognitive impairment group and non cognitive impairment group.The general characteristics,prevalence,biochemistry indexes,comorbidities,and color ultrasound-detected plaque and stenosis in carotid arteries and artery of lower extremity were analyzed and compared between two groups.The logistic multiple regression analysis was used to explore the influencing factors of cognitive dysfunction.Results The differences in age(P=0.027),education (P =0.003),marital status(P=0.000),living situation(P=0.001),hypertension history(P =0.031),type 2 diabetes mellitus (T2DM) history (P =0.036),cerebrovascular disease history (P 0.043)and HbA1c(P=0.032)were statistically significant between cognitive impairment and non cognitive impairment group (all P＜ 0.05).Logistic multiple regression analysis showed that age,marital status,T2DM history,cerebrovascular disease history and comorbidities were positively correlated with cognitive impairment(all P＜0.05).Education was negatively correlated with cognitive impairment(P＜0.05).Conclusions Cognitive impairment is associated with age,education,marital status,T2DM history,cerebrovascular disease history and comorbidities.
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Objective To investigate the effects of water extract of Glycyrrhiza uralensis Fisch.(GUWE) on the activation of RAW264.7 cells and the possible mechanism.Methods RAW264.7 cells were treated with GUWE containing different concentrations of polysaccharide (10, 50, 100, 500 μg/ml).Viability of these cells was analyzed by MTT assay.Phagocytic activity and surface molecules expressed on these cells were detected by flow cytometry.Levels of cytokines were analyzed by ELISA.Western blot assay was performed to analyze the activation of key molecules in TLR4 signaling pathway.Results GUWE at the concentration of 500 μg/ml significantly decreased the viability of RAW264.7 cells, but significantly increased the viability of RAW264.7 cells at concentrations of 50 μg/ml and 100 μg/ml.GUWE significantly enhanced the phagocytic activity of RAW264.7 cells as well as the expression of cytokines and costimulatory molecules in a dose-dependent manner.Further analysis indicated that the activation of RAW264.7 cells induced by GUWE was suppressed by TLR4 inhibitor.Moreover, GUWE enhanced the phosphorylation of NF-kB p65 and TLR4 downstream mitogen-activated protein kinases (MAPKs) including p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK).Conclusion This study indicates that GUWE promotes the activation of RAW264.7 cells through TLR4 signaling pathway.
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Objective To observe the clinical effect ofJiedu-Huayu granule for the Dengue Fever (DF).Methods The patients with DF were randomly divided into the treatment group and control group. Both groups received the conventional treatment, and the treatment group addedJiedu-Huayu granule. The clinical effects were detected.Results At the baseline, the ALT and AST in the treatment were significantly higher than those in the control group (t=2.830,P=0.014;t=2.109,P=0.044). But after treatment, there was no difference between groups. The ALT in the treatment group showed a gradual change and AST recovery time showed short. Compared with control group, the concentration of sVCAM-1 in the treatment group was higher at baseline and the third day (t=2.780,P=0.018;t=2.130,P=0.460), but the concentration of MCP-1 desceased significantly on the 6th day (t=-2.164,P=0.042).Conclusions Compared with the western medicine, the treatment of western medicine andJiedu-Huayu granule could alleviate liver injure, shorten the recovery time, and reduce the concentration of sVCAM-1 and MCP-1.
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Objective:To analyze the immunocontraceptive efficacy of CZP3 DNA vaccine by electric pulse stimulating and the correlation between antibody level and antifertility. Methods: The mice were immunized with 5, 10, 20 and 50 μg DNA vaccine pcDNA3. 0-CZP3 respectively and were stimulated at leg muscle by electric pulse. Detect the antibody level of each mice group and the highest antibody titer by ELISA. After mated with male mice for three weeks,calculated infertility rate of mice,the average litter size of each immune group and did statistical analysis. Results:Compared with the intramuscular injection alone,the electric pulse stimulation could increase serum antibody titers of mice significantly, the antibody titer of 50 μg group which was stimulated by electric pulse reached 1∶4 000. Moreover,the infertility of the mice increased and the mice average litter size reduced along with the increase of CZP3 antibody level significantly. Statistical analysis showed that the antibody level and the average litter size had a negative correlation. Conclusion:The electric pulse stimulation can improve the immune level and reduce the fertility efficiency of mice significantly,therefore establishes a foundation for further application of CZP3 DNA vaccine in stray dog contraception.
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Objectives To investigate the activities of daily living and analysis of the influencing factors among elder hospitalization patients.Methods A series of scales including Activity of Daily Living Scale,Mini-Nutritional Assessment,Mini Mental State Examination,Geriatric Depression Scale 15,Falls Risk Assessment Tool and Euro Qol-5D Questionnaire were used to assess the physical and psychological health status among elder patients at first hospitalization,as well as their social-economic status,and to analyze the activities of daily living and influencing factors.Results Interviewees with less than nine years educational level had 5.93 (95 ％ CI:1.14-33.23)times higher risk for impaired activities of daily living than those with higher education levels.Patients with EQ-5D score ≥1 scale or with cognitive disorder showed 2.86 (95％ CI:1.04-8.05) times or 18.14 (95 ％ CI:1.64-540.63) times higher risks for impaired activities of daily living than their normal controls,respectively.The risks for the decreasing activities of daily living were increased along with ageing (P =0.025).There was a marginal correlation between regular exercise and activities of daily living(P=0.104).Conclusions Educational level,health status and cognitive function are important factors for activities of daily living among elder hospitalization cases and enlarged sample size is required for validation.