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【Objective】 To establish a method to determine the content of the effective ingredient PCA (p-coumaric acid) in Shuang Bailian mixture and to investigate its anti-cancer mechanism. 【Methods】 High performance liquid chromatography (HPLC) was used to determine the content of PCA in Shuang Bailian mixture. The CCK8 method was used to detect the antitumor activity of PCA on esophageal cancer cells and the semi-inhibitory concentration of PCA on esophageal cancer cells. Moreover, the nude mice were used to investigate the anticancer effect of PCA. Western blotting was used to detect the expressions of apoptosis-related proteins (cleaved caspase 3, cleaved PARP, Bad, Bcl-2, PI3K, AKT, p-PI3K and p-AKT) in esophageal cancer cells and tumor tissues of nude mice. 【Results】 The concentration of PCA in Shuang Bailian mixture was 16.84 μg/mL. The linear regression equation of PCA was y=204 402x +360 904 (15-40 μg/mL), the RSD of the precision experiment was 2.66%, the RSD of the stability experiment was 2.35%, 3.22%, 1.58%, and 4.08%, respectively. The RSD of the repeatability experiment was 4.01%. The mean value of the recovery rate was 97.83% and the RSD value was 6.16%. CCK8 results showed that the half maximal inhibitory concentration (IC50) of PCA in KYSE30 and KYSE140 cells was 36 μg/mL and 55 μg/mL, respectively. The results of nude mice tumor experiments showed that after 30 days of administration, the tumor xenograft in control mice continued to increase in size, while the cisplatin group, PCA group, and PCA combined with cisplatin administration could effectively inhibit the growth of transplanted tumors in tumor-bearing mice. In addition, Western blotting results showed that compared with the control group, the cisplatin group, PCA group, and PCA combined with cisplatin group could effectively increase the protein expressions of cleaved caspase 3, cleaved PARP, and Bad, but decrease the protein expressions of Bcl-2, p-PI3K, and p-AKT in tumor tissues and KYSE30 and KYSE140 esophageal cancer cells. 【Conclusion】 The concentration of PCA in Shuang Bailian mixture was 16.84 μg/mL, and the HPLC content determination method conditions were sensitive and stable. PCA may have an active anti-tumor effect by regulating the PI3K/AKT/Bcl-2 signaling pathway and inducing apoptosis in esophageal cancer cells.
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BackgroundCoronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. At present, there is no study to systematically analyse the features of hydroxybutyrate dehydrogenase (-HBDH) in COVID-19 patients with different ages, clinical types and outcomes. MethodsElectronic medical records including demographics, clinical manifestation, -HBDH test results and outcomes of 131 hospitalized COVID-19 patients, with confirmed result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, were extracted and analyzed. ResultsThe -HBDH value in [≥]61 years old group, severe group and critical group, death group all increased at first and then decreased, while no obvious changes were observed in other groups. And there were significant differences of the -HBDH value among different age groups (P<0.001), clinical type groups (P<0.001) and outcome groups (P<0.001). The optimal scale regression model showed that -HBDH value (P<0.001) and age (P<0.001) were related to clinical type. Conclusions-HBDH value increases in some COVID-19 patients, obviously in [≥]61 years old, death and critical group, indicating that patients in these three groups suffer from more serious tissues and organs damage, higher -HBDH value and risk of death. The obvious difference between death and survival group in early stage may provide a approach to judge the prognosis. The accuracy of the model to distinguish severe/critical type and other types is 85.84%, suggesting that -HBDH could judge the clinical type of COVID-19 patients accurately. In brief, -HBDH is an important indicator to judge the severity and prognosis of COVID-19.
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BackgroundCoronavirus disease 2019 (COVID-19) has been declared as a threat to the global. Due to the lack of efficient treatments, indicators were urgently needed during the evolvement of disease to analyze the illness and prognosis, and prevent the aggravation of COVID-19. MethodsPatients general information, clinical type, all CK values and outcome were collected. CK value of all cases during disease course started from different initial time were analyzed. ResultsAll cases underwent 504 tests of CK since symptom onset and the median value was 51.7 (35.0-91.5) U/L. The first median value on the day 8 from exposure onset was 78.1 (69.1-85.8) U/L then showed an upward trend from the day 8 to the day 12 (reaching a peak of 279.3 U/L), finally showed a fluctuation decline after the day 12. The CK median value in critical cases reached the peak (625.5 U/L) on the transforming date, and then decreased rapidly to the normal range. Before death, the CK median value in dead cases firstly increased until the day -14 with a peak as 470.0 U/L, then decreased with fluctuation until day -2, and finally increased again on the day 0. ConclusionsCK reached its peak on the day when it became critical type, dynamic detection of CK can guide clinical judgment of prognosis. The increase of CK is a high risk factor of death. Severe cell damage 2 weeks before death might determines the outcome of the disease even if CK drops to the normal range afterward.
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BackgroundCoronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. There is no study to systematically analyse the features of hydroxybutyrate dehydrogenase (-HBDH) in COVID-19 patients during the periods before and after illness progression, before death and course from exposure onset. MethodsWe collected all included patients general information, clinical type, -HBDH value and outcome, and analyzed -HBDH values within different initial time and different periods. ResultsIn the first 30 days after symptom onset, the -HBDH median value was 156.33 U/L. The first test of -HBDH since exposure onset appeared on the 8th day, it increased from the 8th day to 18th day and decreased after the 18th day. -HBDH median value showed a slight change until it started to increase 1 day before transforming to severe type, while it continued to increase during 4 days before and after transforming to critical type. The -HBDH median value ranged from 191.11 U/L to 455.11U/L before death. Conclusions-HBDH value increases in some COVID-19 patients, obviously in severe type, critical type and death patients, and mainly in 18 days after exposure onset and 10 days after symptom onset. -HBDH increases 1 day before transforming to severe type, continues to increase in critical type and death patients, increases rapidly 5 days before death. The increase of -HBDH suggests that COVID-19 patients have tissues and organs damage, mainly in heart. In brief, -HBDH is an important indicator to judge the severity and prognosis of COVID-19.
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ObjectivesTo study the features of creatine-kinase (CK) in COVID-19 patients with different ages, clinical types and outcomes and quantify the relationship between CK value and clinical type. MethodsAll laboratory confirmed COVID-19 patients hospitalized in Xiangyang No.1 Peoples Hospital were included. Patients general information, clinical type, all CK values and outcome were collected. ResultsThe peak median value of CK in cases aged [≥] 71 years old (appeared at T2) was higher than that in cases aged [≤] 70 years old. There was statistical difference between the two groups (P=0.001). Similarly, the peak in critical cases (appeared at T2) was higher than moderate and severe types, and significant difference were existed among moderate, severe, and critical types (P=0.000). Moreover, the peak value in death group (appeared at T2) was higher than those in survival group. Significant difference was also found between them (P=0.000). According to the optimal scale regression model, the CK value (P=0.000) and age (P=0.000) were associated with the clinical type. ConclusionsDifference of the CK in different ages, clinical types, and outcomes were significant. The results of the optimal scale regression model are helpful to judge the clinical type of COVID-19 patients.
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BackgroundTo characterize C-reactive protein (CRP) changes features from patients with coronavirus disease 2019 (COVID-19) and to quantify the correlation between CRP value and clinical classification. MethodsThis was a bidirectional observational cohort study. All laboratory confirmed COVID-19 patients hospitalized in Xiangyang No.1 Peoples Hospital were included. Patients general information, clinical type, CRP value and outcome were collected. Patients were grouped according to the age, clinical type and outcome, and their CRP were compared. The CRP value, age gender, and clinical type were used to build a categorical regression model to investigate the association between CRP and clinical type. ResultsThe 131 patients aged 50.13{+/-}17.13 years old. There were 4 mild, 88 moderate, 21 severe and 18 critical cases. Statistical significance of CRP median exists between different clinical types and ages. There were 10 deaths and 121 cases have been discharged. The CRP in death group dramatically increased continuously until died, while increased firstly and decreased later in the survivor and survivor in critical type. The categorical regression model also showed that CRP and age had significant coefficient. During the first 15 days from symptom onset, the maximum of CRP ranged between 0.47-53.37 mg/L were related to mild combined with moderate type, ranged 53.84-107.08 mg/L were related to severe type, and 107.42-150.00 mg/L were related to the critical type. ConclusionsCRP showed different distribution feature and existed differences in various ages, clinical types and outcomes of COVID-19 patients. The features corresponded with disease progression.
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BACKGROUNDCoronavirus disease 2019 (COVID-19) has been declared as a threat to the global. Due to the lack of efficient treatments, indicators were urgently needed during the evolvement of disease to analyze the illness and prognosis and prevent the aggravation of COVID-19. METHODSAll laboratory confirmed COVID-19 patients hospitalized in Xiangyang No.1 Peoples Hospital were included. Patients general information, clinical type, CRP value and outcome were collected. CRP values of all patients during disease course from different initial time were analyzed. RESULTSThe 131 enrolled patients were 50.13{+/-}17.13 years old. All cases underwent 724 tests of CRP since symptom onset, 53.18% of the test results were abnormal and the median value was 9.52(2.63-34.10) mg/L. The first median value on the day 8 from exposure onset was 39.08(11.92-47.89) mg/L then fluctuated around it until the day 28. The CRP median increased from 15.93 mg/L to 41.44 mg/L and then decreased to 18.26 mg/L before transformation of severe type, and then increased to 62.25 mg/L on the transforming date. Conversely, the CRP median increased from 56.17 mg/L 102.75 mg/L before transformation of critical type but decreased to 68.68 mg/L on the transforming date. The changes of CRP median over time before death ranged from 77.77 mg/L to 133.52 mg/L. CONCLUSIONSCRP increased before symptom onset and substantially increased during the early-to-mid stage (especially early stage), which was different from other virus-infected diseases. The changes of CRP before the transformation of clinical type was inconsistent with the aggravating of illness. And the CRP maintained over 100.00 mg/L prompted poor prognosis.
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BackgroundThe stage of CT images was rarely studied and the relationship between the severity of Coronavirus Disease 2019 (COVID-19) and CT images has not been studied based on systematic quantitative analysis currently. PurposeTo investigate the staging duration and classification of CT images of patients with COVID-19 based on quantitative analysis. Materials and MethodsThis is an ambispective observational cohort study based on 125 patients with COVID-19 from Jan 23 to Feb 28, 2020. The stage of CT and pulmonary lesion size were quantitatively analyzed. The categorical regression analysis based on optimal scale (CATREG) was performed to evaluate the association of CT score, age, and gender with the clinical type. ResultsThe CT images of 125 patients with COVID-19 (50.13 {+/-} 16.91 years, 66 women) were analyzed in this study. Except for pre-early stage, the duration of early, progression-consolidation, and dissipation stage of CT images was 3.40 {+/-} 2.31, 10.07 {+/-} 4.91, and 20.60 {+/-} 7.64 days, respectively. The median CT score was 5.00 (2.00-8.50) during the first 30 days, which reached a peak on the 11th day. Significant differences were found between the median CT scores of different clinical types (P<0.05). Besides, the age was correlated with the clinical type (P<0.001), the CT scores of 0.00-11.50, 11.50-16.00, and 16.00-20.00 were separately correlated with the moderate, severe, and critical type with the output accuracy 69.60%. ConclusionThe four-stage staging method based on quantitative analysis is consistent with the change rules of staging features and COVID-19. Quantitative study by scoring pulmonary lesion sizes accurately revealed the evolvement of pulmonary lesions and differences between different clinical types. SummaryQuantitative study of the stage duration and classification of chest CT images can objectively reveal the relationship between Coronavirus Disease 2019 (COVID-19) and chest CT images. Key Results1. A four-stage staging method was proposed. Except for pre-early stage, the duration of early, progression-consolidation, and dissipation stage of CT images was 3.40 {+/-} 2.31, 10.07 {+/-} 4.91, and 20.60 {+/-} 7.64 days, respectively. 2. The severer the disease, the higher the median CT scores and their peak value. 3. The CT scores of 0.00-11.50, 11.50-16.00, and 16.00-20.00 were separately correlated with the moderate, severe, and critical type.
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BackgroundAs the spreading of the COVID-19 around the global, we investigated the characteristics and changes of symptoms in COVID-19 patients. MethodsThis was an ambispective observational cohort study, and 133 confirmed COVID-19 patients were included and all symptoms over the course were analyzed qualitatively. The symptoms, their changes over the course in the cohort and in the different clinical types, etc. were illustrated. Differences in different periods and severities were analyzed through Chi square test, association with severity was analyzed through LASSO binomial logistic regression analysis. Inter-correlation and classification of symptoms were completed. Major symptoms were screened and their changes were illustrated. ResultsA total of 43 symptoms with frequencies as 6067 in this cohort. Differences of symptoms in different stages and clinical types were significant. Expectoration, shortness of breath, dyspnea, diarrhea, poor appetite were positively but vomiting, waist discomfort, pharyngeal discomfort, acid reflux were negatively correlated with the combined-severe and critical type; dyspnea was correlated with the critical type. The 17 major symptoms were identified. The average daily frequency of symptoms per case was decreased continuously before the transition into the severe type and increased immediately one day before the transition and then decreased. It was decreased continuously before the transition date of the critical type and increased from the transition into the critical type to the next day and decreased thereafter. Dyspnea (P<0.001), shortness of breath (P<0.01) and chest distress (P<0.05) were correlated with death and their corresponding coefficient was 0.393, 0.258, 0.214, respectively. ConclusionThe symptoms of COVID-19 patients mainly related to upper respiratory tract infection, cardiopulmonary function, and digestive system. The mild type and the early stage in other types mainly related to upper respiratory tract infection. The cardiopulmonary function and digestive system associated symptoms were found in all other types and stages. Dyspnea was correlated with critical type and dyspnea, shortness of breath, and chest distress were correlated with death. Respiratory dysfunction (or incompleteness) associated symptoms were the characteristic symptoms. The changes of symptoms did not synchronously with the changes of severity before the transition into the severe or critical type.
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BackgroundThe pandemic of coronavirus disease 2019 (COVID-19) has become the first concern in international affairs as the novel coronavirus (SARS-CoV-2) is spreading all over the world at a terrific speed. The accuracy of early diagnosis is critical in the control of the spread of the virus. Although the real-time RT-PCR detection of the virus nucleic acid is the current golden diagnostic standard, it has high false negative rate when only apply single test. ObjectiveSummarize the baseline characteristics and laboratory examination results of hospitalized COVID-19 patients. Analyze the factors that could interfere with the early diagnosis quantitatively to support the timely confirmation of the disease. MethodsAll suspected patients with COVID-19 were included in our study until Feb 9th, 2020. The last day of follow-up was Mar 20th, 2020. Throat swab real-time RT-PCR test was used to confirm SARS-CoV-2 infection. The difference between the epidemiological profile and first laboratory examination results of COVID-19 patients and non-COVID-19 patients were compared and analyzed by multiple logistic regression. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the potential diagnostic value in factors, which had statistical differences in regression analysis. ResultsIn total, 315 hospitalized patients were included. Among them, 108 were confirmed as COVID-19 patients and 207 were non-COVID-19 patients. Two groups of patients have significance in comparing age, contact history, leukocyte count, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate (p<0.10). Multiple logistic regression analysis showed age, contact history and decreasing lymphocyte count could be used as individual factor that has diagnostic value (p<0.05). The AUC of first RT-PCR test was 0.84 (95% CI 0.73-0.89), AUC of cumulative two times of RT-PCR tests was 0.92 (95% CI 0.88-0.96) and 0.96 (95% CI 0.93-0.99) for cumulative three times of RT-PCR tests. Ninety-six patients showed typical pneumonia radiological features in first CT scan, AUC was 0.74 (95% CI 0.60-0.73). The AUC of patients age, contact history with confirmed people and the decreased lymphocytes were 0.66 (95% CI 0.60-0.73), 0.67 (95% CI 0.61-0.73), 0.62 (95% CI 0.56-0.69), respectively. Taking chest CT scan diagnosis together with patients age and decreasing lymphocytes, AUC would be 0.86 (95% CI 0.82-0.90). The age threshold to predict COVID-19 was 41.5 years, with a diagnostic sensitivity of 0.70 (95% CI 0.61-0.79) and a specificity of 0.59 (95% CI 0.52-0.66). Positive and negative likelihood ratios were 1.71 and 0.50, respectively. Threshold of lymphocyte count to diagnose COVID-19 was 1.53x109/L, with a diagnostic sensitivity of 0.82 (95% CI 0.73-0.88) and a specificity of 0.50 (95% CI 0.43-0.57). Positive and negative likelihood ratios were 1.64 and 0.37, respectively. ConclusionSingle RT-PCR test has relatively high false negative rate. When first RT-PCR test show negative result in suspected patients, the chest CT scan, contact history, age and lymphocyte count should be used combinedly to assess the possibility of SARS-CoV-2 infection.
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ObjectiveTo describe the epidemiological and clinical characteristics of the Coronavirus Disease 2019 (COVID-19) hospitalized patients and to offer suggestions to the urgent needs of COVID-19 prevention, diagnosis and treatment. MethodsWe included 102 confirmed COVID-19 cases hospitalized in Xiangyang No.1 peoples hospital, Hubei, China until Feb 9th, 2020. Demographic data, laboratory findings and chest computed tomographic (CT) images were obtained and analyzed. FindingsAll cases were confirmed by real-time RT-PCR, including 52 males and 50 females with a mean age of 50.38 years (SD 16.86). Incubation time ranged from one to twenty days with a mean period of 8.09 days (SD 4.99). Fever (86[84.3%] of 102 patients), cough (58[57%]), fatigue (28[27%]), shortness of breath (24[23%]), diarrhea (15[15%]), expectoration (13[12%]), inappetence (11[10%]) were common clinical manifestations. We observed a decreased blood leukocyte count and lymphopenia in 21 (20.6%) and 56 (54.9%) patients, respectively. There were 66 (68%) of 97 patients with elevated C-reactive protein levels and 49 (57.6%) of 85 with increased erythrocytes sedimentation rate. Higher levels of procalcitonin and ferritin were observed in 19 (25.3%) of 75 and 12 (92.3%) of 13 patients, respectively. Eight patients were admitted to intensive care unit (ICU), six developed respiratory failure, three had multiple organ failure and three died. The cumulative positivity rate over three rounds of real-time RT-PCR was 96%. One-hundred patients were found with typical radiological abnormalities in two rounds of chest CT scans, indicating a 98% consistency with real-time RT-PCR results. InterpretationMost COVID-19 patients in Xiangyang were secondary cases without sex difference, and the rate of severe case and death was low. Middle-to-old-age individuals were more susceptible to the virus infection and the subsequent development of severe/fatal consequences. The average incubation period was longer among our patients. We recommend prolonging the quarantine period to three weeks. Three times real-time RT-PCR plus two times CT scans is a practical clinical diagnosis strategy at present and should be used to increase the accuracy of diagnosis, thereby controlling the source of infection more effectively.
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Objective:To comprehensively analyze the medical resources and services supply in the cancer field of China.Methods:Data of 2018 were sampled from 41 tertiary public cancer hospitals in China, and the factor analysis method was used to extract common factors in resources or services, scoring respectively. Pearson correlation analysis was used in the collinearity test of the variables of both groups of common factors, while the second-order clustering method was used to analyze characteristic differences between the hospitals, and category difference was compared with t test. Results:Resource evaluation covered the two dimensions of basic resources(medical service and basic assurance resources)and high-end resources(high-end talents and academic resources). Service evaluation covered the two dimensions of medical service assurance(clinical services and basic assurance)and disciplinary sphere of influence(discipline construction and clinical efficiency). The factor of basic manpower and beds was significantly correlated with that of medical service and basic assurance( r=0.811, P<0.001), while the factor of high-end talents and academic resources was significantly correlated with that disciplinary construction and resource efficiency( r=0.906, P<0.001). The second-order cluster analysis found the 41 cancer hospitals as two categories, with the first category of five in Guangdong, Shanghai, Beijing and Tianjin, and the second category of the rest 36 hospitals. Significant differences were found between the two categories in terms of resource scoring, service scoring, high-end resources and disciplinary sphere of influence( P<0.001). Meanwhile, the GDP per capita of the cities in which these hospitals are located also had significant differences( P<0.001). Conclusions:Development of public tertiary cancer hospitals in China was imbalanced, as their differences were mainly found in levels of disciplinary development and efficiency of clinical services, which were closely related to the high-end talents and academic resources of the hospital in question.Furthermore, high quality medical care was mostly located in regions of higher development. The authors recommend to take a balanced consideration of the differences and distribution of cancer care services in China, in terms of performance classification of public hospitals and establishment of regional cancer centers of the country.
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The inverse cancer comorbidity in schizophrenia patients may be related to the genetic factors ,involving the regu‐lation of apoptosis .The tumour suppressor gene TP53 ,involved in neural apoptosis ,is one of the potential candidate genes associat‐ed with schizophrenia which might reduce colorectal cancer risk .We recruited 270 schizophrenia patients and 312 colorectal cancer patients without schizophrenia .To examine the genetic association between schizophrenia and colorectal cancer ,we analysed eight SNPs (rs12951053 ,rs1625895 ,rs2909430 ,rs9895829 ,rs1042522 ,rs8079544 ,rs8064946 ,rs17806770) covering 14 .35 kb in the re‐gion of TP53 .We observed that one of the eight genetic polymorphisms showed statistically significant differences between the colo‐rectal cancer subjects and the schizophrenia subjects (rs12951053 ,P=0 .000 1 ,OR 1 .70 ,95% CI 1 .30-2 .23) .In addition ,the hap‐lotype of A‐G (rs12951053‐rs8064946) ,giving a global P=0 .001 8 ,was the most significant .Our data indicate that the polymor‐phisms of rs12951053 in TP53 confer reduced susceptibility to colorectal cancer and suggest a potential protective mechanism a‐gainst colorectal cancer in the schizophrenia patients of Han Chinese origin .
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Objective To investigate the effect of electroacupuncture(EA)in improving the reconstruction of synapse after cerebral ischemia.Methods Forty-five Wistar rats were divided into 3 groups:sham-operated group,ischemia group and EA group.The number density(Nv)of synapses and the surface density(Sv)of synaptic joint band were observed 1 hour,1 day,3 days,1 week and 3 weeks after ischemia and EA, respectively.Heat-coagulation-induced occlusion of the middle cerebral artery was performed to establish the model of focal cerebral ischemia.EA group received EA on the acupoints of Baihui and Dazhui.The changes of synaptie structure,Nv and Sv as well as the influence of EA on the above indexes were observed in different time.Results There existed significant decrease of Nv and Sv 1 hour,1 day and 3 days after establishment of models in the isehemia group(P0.05).Conclusion EA can reduce the cerebral ischemic injury by increasing the synaptic amount and area in the cortex of rat model of cerebral isehemia at early stage,promoting the cerebral recovery after ischemia,which will provide substantial morphological basis for the improvement of synaptic reconstruction and recovery from cerebral isehemia by EA at different time after ischemic cerebral injury.
