Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

OBJECTIVE: To investigate the risk factors for acute myocardial injury in coronavirus disease 2019 (COVID-19) patients. METHODS: This is a retrospective analysis of a COVID-19 cohort, in which 149 confirmed COVID-19 patients enrolled were divided into the group of myocardial injury (19 cases) and the group of non-myocardial injury (130 cases). Myocardial injury was defined according to Fourth universal definition of myocardial infarction released by European Society of Cardiology (ESC) in 2018, that cardiac troponin (cTn) was above 99th percentile of the reference level. Clinical information and results of laboratory tests of the eligible patients were collected. Factors associated with myocardial injury in COVID-19 patients were evaluated. RESULTS: Compared with the group of non-injury, the patients in the group of injury were older and had a larger proportion of severe or critical cases (P < 0.05), higher respiratory rate and lower percutaneous oxygen saturation (SpO₂) without oxygen therapy on admission (P < 0.05). All inflammatory indexes except for tumor necrosis factor α (TNF-α) showed significant elevation in the patients of the group of injury (P < 0.05). Analyzed by Spearman correlation test, we showed that the levels of circulatory cTnI were in positive correlation with the levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, receptor of interleukin-2 (IL-2R), interleukin-6 (IL-6) and interleukin-8 (IL-8) (ρ > 0, P < 0.05). Lower SpO₂ without oxygen therapy on admission (OR: 0.860, 95%CI: 0.779-0.949, P=0.003) and higher plasma IL-6 levels (OR: 1.068, 95%CI: 1.019-1.120, P=0.006) were independent risk factors for acute myocardial injury in the patients with COVID-19 by multivariate Logistic regression analyses. CONCLUSION Hypoxic state and inflammation may play a key role in the pathogenesis of acute myocardial injury in COVID-19 patients.
Biomarkers ; COVID-19 ; Humans ; Hypoxia ; Inflammation ; Retrospective Studies ; Risk Factors ; SARS-CoV-2

AIM:To investigate the effect of 27nt-microRNA (27nt-miRNA) on the expression of smooth muscle 22α protein (SM22α) and the cell viability, migration and phenotypic changes of vascular smooth muscle cells (VSMCs).METHODS:The highly expression plasmids of 27nt-miRNA, and anti-27nt-miRNA and negative control plasmids were constructed, packaged with lentivirus and transfected into the rat primary VSMCs.Platelet-derived growth factor BB (PDGF-BB) was added to induce VSMCs phenotype conversion.The cell viability was measured by MTT assay.The migration ability was detected by scratch assay.The mRNA and protein expression of SM22αwas determined by RT-PCR, immunocytochemical staining and Western blot.RESULTS:Compared with normal group, the cell viability in PDGF-BB group was increased (P<0.05) , the migration ability was increased (P<0.05) and the expression of SM22αat mRNA and protein level was decreased (P<0.05).Compared with negative control lentiviral group, the cell viability in 27ntmiRNA over-expression group was decreased (P<0.05) , the migration ability was decreased (P<0.05) , and the mRNA and protein expression of SM22αwas increased (P<0.05).While in anti-27nt-miRNA group, the cell viability was increased (P<0.05) , the migration ability was increased (P<0.05) , and the mRNA and protein expression of SM22αwas decreased (P<0.05).CONCLUSION:27nt-miRNA significantly increases the expression of SM22α, while inhibits the viability and migration ability of VSMCs, and inhibits its phenotypic shift from contractile to synthetic.

BACKGROUND:Stem cells combined with a three-dimensional scaffold have great potential for the treatment of osteoporotic bone defects. OBJECTIVE:To introduce the application of stem cells combined with the three-dimensional scaffold in repairing osteoporotic bone defects. METHODS:A computer-based search of PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases was performed for relevant articles published from 2007 to 2017 with "stem cells, scaffold, osteoporosis, bone defects" as key words in English and Chinese, repsectively. Initially, 142 articles were retrieved, and finally 45 articles were included in result analysis. RESULTS AND CONCLUSION:Due to the potential of self-renewal and multilineage differentiation, stem cells can be used to repair or regenerate damaged tissues, which are considered as an ideal cell source for the treatment of diseases in orthopedics. The suitable scaffold can provide a favorable microenvironment for repairing the attachment and growth of the cells related to the bone defect, which can promote the healing without additional side effects. Furthermore, stem cells combined with three-dimensional scaffolds provide a promising clinical application for the treatment of osteoporotic bone defects by regulation of bone metabolism. In addition, gene-modified stem cells with three-dimensional scaffolds bring a huge potential in the treatment of osteoporotic bone defects. In conclusion, the combination of stem cells and three-dimensional scaffolds provides a new approach for the treatment of osteoporotic bone defects, which may be one of the future therapeutic strategies.

The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
Drugs, Chinese Herbal ; analysis ; Fractals ; Medicine, Chinese Traditional ; Powders ; Quantitative Structure-Activity Relationship ; Synchrotrons ; Technology, Pharmaceutical ; Tomography, X-Ray Computed

Objective To analyze the status and influencing factors of health literacy among residents in Chaoyang District, Beijing City.Methods Through multi -stage stratified cluster sampling method in Chaoyang District,a total of 1 028 residents aged 1 6 to 69 years were selected.They were interviewed by using the questionnaire based on Chinese Citizens Health Literacy -Basic Knowledge and Skills (Trial)and modified by experts.Non -conditional logistic regression was used to evaluate the influencing factors of health literacy.Results The health literacy rate among the respondents was 21 .21 %.The health literacy rates of 7 issues including scientific view of health,safety and first aid,infectious diseases prevention,access to information and applications,basic medical care,chronic diseases prevention and daily health care were 59.05%,55.84%,41 .34%,27.53%,27.1 4%,1 0.31 % and 6.61 % respectively.The health literacy rates of basic knowledge and concepts,health lifestyle and behaviors with basic skills were 25.58%,1 8.09% and 32.20%respectively.The result of multiple logistic regression showed that living area and education level were the influence factors of health literacy.Conclusion According to the characteristics of living area and education level of residents,some measures should be carried out to improve the residents'health literacy,especially focused on the lifestyle and behavior intervention.

OBJECTIVEThe health surveillance proposal for chromate exposed workers was provided and analyzed on the evidence-based study and then to be improved.

METHODFirstly, the related literatures were searched about liver damage, micronuclei, urinary chromium and hexavalent chromium exposure in Evidence Based Medicine Reviews such as Cochran library, OVID Medline, Web of knowledge in December 2011; and then, these literatures were reviewed in according to inclusion and exclusion criteria; 22 articles totally were retrieved, evaluated and classified in according to the grading standard by Oxford Centre for Evidence-based Medicine.Finally, field epidemiological investigation was further adopted to confirm the efficiency and feasibility of this proposal, combined with cost-effectiveness analysis:the ratio of total cost divided survival years was used to express the cost-effectiveness.

RESULTOnly the glutamic pyruvic transaminase test could not reflect liver damage caused by chromate exposure well; Urinary chromium correlated well with the index reflecting body damage caused by chromate exposure; Binucleated cells micronucleus index in peripheral blood lymphocyte could reflect the genetic damage caused by chromate exposure. As for health economic evaluation of chromate lung cancer, the value of cost/effectiveness was ¥42 321.61 per year that was far below the value of common people (¥252 868.97 per year) .

CONCLUSIONIt was suggested that serum glutamic pyruvic transaminase test should be replaced by liver function test, urinary chromium should be classified as a compulsory index and binucleated cells micronucleus index in peripheral blood lymphocyte should be supplied as a recommended index.

Objective To perspectively evaluate the long-term efficacy of low dose leflunomide in treatment of rheumatoid arthritis.Methods Twenty-eight patients with rheumatoid arthritis were randomly divided into treatment group( n =15 ) and control group ( n =13 ).The patients in treatment group were treated with low dose leflunomide( omitting the loading dose) and with maintenance dose of 10 mg/day.And the patients in control group were treated with sulphasalazine in the dose of 1.5 ～ 2.0 g/d.The observation lasted for 18 months and the observed indicator were as follows:( 1 ) The primary efficacy indicators:counts of swollen and tender joints,overall assessment of disease status made by patients and physicians; ( 2 ) Secondary efficacy indicators:pain visual analogue scale,duration of morning stiffness,health assessment questionnaire (HAQ),Creaction protein,the American College of Rheumatology Outcome Assessment (ACR20,50).Results Eighteen months after treatment,the primary efficacy indicators in the treatment group were superior to the control group ( swollen joint counts:( - 8.5 ± 6.3 ) vs ( - 7.9 ± 6.4) ; overall assessment by patients:( - 1.4 ± 0.8 ) points vs ( - 1.2 ± 0.6) points; overall assessment by physicians:( - 1.4 ± 1.2 ) points vs ( - 1.3 ± 0.9 ) points; P ＜0.01 ).In the secondary efficacy indicators,pain visual analogue scale,duration of morning stiffness and health assessment questionnaire(HAQ) in the treatment group were significantly improved compared with the control group(VAS score:( - 32.4 ± 23.7) points vs ( - 31.6 ± 24.8) points; duration of morning stiffness:( [ - 97.8 ± 6.2 ] min vs [ - 92.4 ± 5.2 ] min; HAQ:[ - 0.62 ± 0.08 ] points vs [ - 0.57 ± 0.02 ] points,P ＜0.01 ),there was no significant difference on the percentage of patients achieving ACR20 standard between the treatment group and the control group (76.9％ vs 75.0％,P ＞ 0.05 ),but there was significant difference on the percentage of patients achieving ACRS0 standard between the treatment group and the control group( 61.5％ vs 47.0％,P ＜ 0.05 ).The gastrointestinaladverse reactions for patients in the treatment group were mild and there were 2 cases of elevated blood pressure,2 cases of elevated liver enzymes and 2 cases out of the trail,in the control group,there was 1 case out of the trial.Conclusion The long-term treatment of active rheumatoid arthritis with low dose leflunomide can achieve exact efficacy and good tolerability compared with the treatment with sulfasalasine.

ObjectiveTo observe the thyroid status of pregnant women during the 1st and 2nd trimester of gestation,and its role in brain and neural development of their offspring's.MethodsFrom 2008 to 2009,pregnant women from nine townships of two counties in Wushi and Baicheng in Aksu prefecture of Xinjiang were selected as research subjects according to the survey standard.After informed consent signed,their urinary iodine,serum thyroid stimulating hormone(TSH) and free thyroxin(FT4) were analyzed.The value of thyroid hormone of normal pregnant women was used in diagnosis of subclinical hypothyroidism and hypothyroxinemia in pregnant women.From 2010 to 2011, The brain and neural development status among offspring born by those pregnant women were evaluated with DDST.In accordance with the results of Denver Development Screen Test (DDST) screening,pregnant women were classified into survey and control groups,and the survey group was the suspicious and abnormal of the result of DDST screening(delay),the control group was normal of the result.According to gestational age,pregnant women were divided into 4 gestation groups:G1(6 to 13 weeks),G2(14 to 18 weeks),G3 ( 19 to 23 weeks) and G4(24 to 28 weeks).ResultsA total of 396 cases of pregnant women during the 1st and 2nd trimester of gestation were investigated(survey group 102 cases,control group 294 cases).The median value of urinary iodine concentration among pregnant women in survey group was 152.4 μg/L The prevalence of subclinical hypothyroidism and hypothyroxinemia among pregnant women was 10.78％(11/102) and 3.93％(4/102),respectively.In control group,the median value of urinary iodine concentration was 180.0 μg/L The prevalence of subclinical hypothyroidism and hypothyroxinemia among pregnant women was 7.48％ (22/294) and 4.42％ (13/294),respectively.During the pregnant period from G1 to G3,the median serum TSH of pregnant women in DDST survey group (2.24,3.49,2.85 mU/L) was higher than that of DDST control group( 1.59,2.70,2.28 mU/L).Especially,the difference of TSH between the two groups during the period of G3 was statistically significant (t =4.906,P ＜ 0.05 ).ConclusionsHypothyroidism tendency of pregnant women during the period from gestation week 19th to 23rd may be an important factor in the development of brain abnormalities of their offsprings.