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 compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Aim To study the antiviral anrl antipyretic mechanism of Phillvrin in vitro and in vivo.Methods By respiratory virus infection cell model, SI index and antiviral activity of forsythia glycosides virus activity in vitro were detected.A mouse model of influenza virus infection was established, and hemagglutination titer, lung index, lung histopathology pathology were detec¬ted.Hemagglutination titer, lung index, lung histopa¬thology pathology were observed and in vivo anti-influ¬enza virus and pneumonia effects were investigated.Dry yeast induced rat fever model was established, temperature and plasma and hypothalamus thermoregu¬lation and inflammation of the related factors were test¬ed , and its antipyretic mechanism was investigated.By AutoDock Vina software for molecular docking, the docking results were plotted with PyMol software.Re¬sults Phillyrin had certain inhibitory effects on H3N2, RSV, E71 , ADV-3, HSV-1 and HSV-2 (SI >2).Phillyrin could reduce hemagglutination titer of infected lung tissue, decrease lung index, and alleviate lung lesions, especially interstitial pneumonia.Phill- vrin could also significantly reduce the body tempera¬ture of rats with fever, and its antipyretic mechanism might he related to the decrease of PGE2 and IL-ip levels in plasma and hypothalamus of rats.Molecular docking results showed that the binding energies of Phillyrin with a-MSH, IL-lp, PEG2, A VP, cAMP and other proteins were all less than - 5 kcal • mol 1.Conclusions Phillyrin has obvious antiviral, antipy-retic and improvement of pulmonary inflammatory le¬sions, and it is speculated that it can play an anti-in¬fluenza effect through "treating both symptoms and root causes".

Objective:To evaluate the safety of two inactivated COVID-19 vaccines in a large-scale emergency use.Methods:Based on the "Vaccination Information Collection System", the incidence data of adverse reactions in the population vaccinated with the inactivated COVID-19 vaccines developed by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd, respectively, in emergency use were collected, and the relevant information were analyzed with descriptive epidemiological and statistical methods.Results:By December 1, 2020, the vaccination information of 519 543 individuals had been collected. The overall incidence rate of adverse reactions was 1.06%, the incidence rate of systemic adverse reactions was 0.69% and the incidence rate of local adverse reactions was 0.37%. The main systemic adverse reactions included fatigue, headache, fever, cough and loss of appetite with the incidence rates of 0.21%, 0.14%, 0.06%, 0.05% and 0.05%, respectively; the main local adverse reactions were injection site pain and injection site swelling with the incidence rates of 0.24% and 0.05%, respectively.Conclusion:The two inactivated COVID-19 vaccines by Beijing Institute of Biological Products Co., Ltd and Wuhan Institute of Biological Products Co., Ltd showed that in the large-scale emergency use, the incidence rate of general reactions was low and no serious adverse reactions were observed after the vaccinations, demonstrating that the vaccines have good safety.

To study the toxicity-decreasing and synergistic effect of intracellular and extracellular polysaccharides from Phellinus igniarius on S180 mice. The PIP and PIE were extracted from the products of liquid submerged fermentation of P. igniarius. Transplanting S180 mice tumor models were established so as to observe the changes in tumor inhibiting rate, indexes of the spleen and thymus, body weight, peripheral blood cells and IFN-gamma levels when CTX was used alone and when used in combination with the PIP and PIE from P. igniarius. The results indicate that the PIP and PIE from P. igniarius can increase the activity of body immunity, attenuate the toxicity of CTX as well, and improve the anti-tumor effects.
Animals ; Antineoplastic Agents ; isolation & purification ; pharmacology ; Basidiomycota ; chemistry ; classification ; isolation & purification ; Body Weight ; drug effects ; Cyclophosphamide ; pharmacology ; Disease Models, Animal ; Drug Synergism ; Female ; Interferon-gamma ; blood ; Male ; Medicine, Chinese Traditional ; Mice ; Neoplasm Transplantation ; Plant Extracts ; Polysaccharides ; isolation & purification ; pharmacology ; Random Allocation ; Sarcoma 180 ; drug therapy ; pathology ; Spleen ; pathology ; Thymus Gland ; pathology

Objective To investigate the expressions of Transforming Growth Factorβ2 (TGF-β2) and Smad3 in human gliomas associated with pathologic grading. Methods The expressions of TGFβ2 and Smad3 protein were detected with SP immunhistochemistry in 80 human glioma specimens. The Kapan-Meier survival curves of progression-free survival time and overall survival time in different expression levels was compared with log-rank. Results The expression of TGFβ2 and Smad3 correlated with the pathological grading (r=0.545, r=0.570, P<0.01). Both progression-free survival time and overall survival time were significantly different between low expression group and high expression group (P<0.05). Conclusion Both TGF-β2 and Smad3 correlate well with the occurrence and differentiation of human gliomas,which help for the diagnosis, treatment and prognosis judgment．

Objective To establish C6 glioma model in rat brain and to study its biological behavior(such as the incidence of tumor development, the process of cell invasion pathological characteristics of C6 and neoangiogenesis, the spontaneous regression of experimental gliomas and the best experimental time window).Methods C6 tumor cells and DMEM were implanted into the right caudate of 50 male Wistar rats. 9 rats implanted DMEM is the control group. The animals were examined by MRI and pathological staining at postoperative day (POD) 3, 7, 14, 21,28, 35, and 50. Matrix metalloproteinases-2 (MMP-2) and CD31 immunohistochemistry staining were used to study the histopathological features of the developed tumor. Methodology, physical findings and biological behavior were also discussed. Results 45 Wistar rats survived after surgery and tolerated MRI procedures well. On POD 7, there was a focal signal at the implantation site. The C6 cells sprout to the surroundings along the nerve fiber. During the day 14～28, the tumor exhibited a marked increase in size with focal mass effect, and immunohistochemical-staining shows MMP-2 and CD31 is overexpression; C6 cells were aggregated and blood brain barrier were destroyed greatly. Most of the tumor bearing rats died within 30 days. But, C6 cells in the two rats retrogress spontaneously after more leucocytes rounded 28 days. HE staining shows tumors.Conclusion The characteristics of rat C6 brain tumor model mimicked the human tumor with respect to its development, progression, and invasion. Although, part of C6 tumor spontaneously regressed, it is a useful animal model of glioblastoma for pre-clinical evaluation of various therapeutic strategies for the management of glioblastoma. The best experimental time window is 14 to 28 days.

Objective To evaluate the use of diffusion-weighted imaging(DWI)for early detection of tumor response to Angiostatin-Endostatin(Statin-AE)fusion gene therapy in a rat C6 glioma model.Methods Fifty male wistar rats with C6 tumor cells implanted into the striatum were examined by a 3.0T MR scanner,then the rats beating tmors were divided into two groups,treatment group and control group.Rats in the treatment group received 107 plaque forming unit(pfu)recombinant herps simplex viral (R-HSV)mediated Statin-AE fusion gene therapy on day 7,and then the tumors were conformed on MRI.Conventional MR and DWI examination were acquired on 1,2,3 weeks after implantation with a 5-inch surface coil.Two(1 w),eight(2 w)and all the residual rats(3 w)of each group were sacrificed to perform the histopathological examination after each MBI examination.Pretreatment and post treatment tumor volulnes and apparent diffusion coefficient(ADC)values were calculated.Rank sum test and t test were employed for statistical analysis.Results On MRI,43 rats demonstrated tumors on day 7 with a successful rate of 86%,On week 2,the tumor volumes of the controh and treatment group were 90.6 and 91.64 mm3,with no significant difference(Z=-0.14,P＞0.05).On week 3,the tumor volumes of the controls and treatment group were 156.64 and 29.64 mm3,and a significant difference was observed(Z=-3.45,P＜0.01).On week 2.the ADC values of the tumor centers of the treatment group and the control group were (1.20±0.25)×10-3 and(0.99±0.08)×10-3 mm2/s,and the values of the tumor peripheral parts of the two groups were(1.00±0.25)×10-3 and(0.83±0.12)×10-3mm2/s,the ADC values of both tumor centers and peripheral parts of the treatment group were significantly higher than those of the control group (t=-0.82 and-0.46,P＜0.05).On week 3,the ADC values of the tumor centers of the treatment group and the control group were(0.92±0.21)× 10-3 and(0.99±0.09)×10-3mm2/s,and the values of the tumor peripheral parts of the two groups were(0.81±0.19)×10-3 and(0.78±0.11)×10-3 mm2/a,there were no statisfical difference between the two groups(t=0.82,and-0.46,P＜0.05).HE stained slices showed more prominent tumor interstifial edenla.swelling and death of tumor cells in the treated rats than the controls.Conclusions Combination of conventional MRI and DWI can be powerful to monitor tumor progression and therapy effecL Conventional MRI showed that the therapy slow the tumor progression in size while DWI demonstrated the tumor response even earlier than size change.DWI has potential use forthe detection of early response to antiangiogenic gene therapy.

BACKGROUND:Hepatocyte transplantation has attracted more and more attention as a therapeutic measure for liver failure and genetic metabolic liver diseases.OBJECTIVE:TO evaluate the efficacy and safety of human hepatocyte transplantation in treating hepatitis B related liver failure in one case by a 2-year follow-up.DESIGN:A case-report of 2-year follow-up.SETTING:No.9 Department of Infectious Diseases,Bioengineering Research Room,the 302 Hospital of Chinese PLA.PARTICI PANT:One inpatient with hepatitis B related liver failure was selected from the 302 Hospital of Chinese PLA.and she was diagnosed according the laboratory tests.The transplanted hepatocytes were originated frOm the healthy liver of a 24-year-old man,who had signed the protocol for liver donation before death.METHODS:The hepatocyte transplantation was completed in the Department of Radiology,the 302 Hospital of Chinese PLA in December 2004.Liver was isolated to obtain human primary hepatocytes, and then cryopreserved.The hepatocytes were transplanted into recipient spleen via femoral vein after resuscitation.The clinical symptoms,changes of blood biochemical indexes,and changes of spleen MRI signals were observed before and after operation.The patient was reexamined every half a year after operation, including liver function, blood coagulation function,B-mode ultrasonography,gastroscopy and MRI,and she was followed up for 2 years. MAIN OUTCOME MEASURES:Liver function,blood coagulation function, imaging indexes, immunological indexes,complication and rejection.RESULTS:①Totally(1-2)×1010 hepatocytes were harvested,and the viability of rewarmed hepatocytes was 60%,and finally 2×109 hepatocytes were transplanted.②Two months later,the clinical symptoms of the recipient were obviously ameliorated,and serum bilirubin and aspartate aminotransferase(AST)were obviously decreased,while prothrombin activity was markedly increased.20 months later,the MRI results showed that there was hepatocyte image in spleen.Two years after operation.the total bilirubin level was 20 μmol/L,direct bilirubin level was 7 μmol/L, alanine aminotransferase was 416.75 nkat/L,AST was 533.44 nkat/L,albumin was 37 g/L,prothrombin activity was 90%,which were all obviously ameliorated as compared with those before operation(474.5 μmol/L,340.3 μmol/L,400.08 nkat/L,1 200.24 nkat/L,38 g/L,25%).The patient left the hospital 2 months later and could do light-burdened job.No complications of hydroperitonia and liver function failure, etc.were observed,and no rejection occurred.Several reexaminations by B-mode ultrasonography all indicated the further aggravations of liver cirrhosis and esophageal varices.She was admitted to hospital for twice because of esophageal varices bleeding,and cured by endoscopic variceal sclerosis therapy.CONCLUSION:Hepatocyte transplantation can ameliorate liver function without rejection,but it cannot relieve portal hypertension.

BACKGROUND: As indicated by experiments on animal, cytokine has regulatory effects on sleep. Clinical research has found abnormal level of cytokine in patients with depression. Sleep rhythm disorder is a common symptom of depression; however, the relationship between cytokine and sleep has hardly been conducted at home and abroad.OBJECTIVE: To explore the relationship between abnormal level of cytokine and clinical characteristics of sleep disorder so as to provide theoretical basis for early intervention and functional detection of sleep disorder in patients with depression.DESIGN: A case-controlled study using the patients with depression as the subjects and normal persons as the controls.SETTING: Two wards of the Department of Psychiatry of a university hospital.PARTICIPANTS: The study was completed in the Department of Psychiatry, Second Affiliated Hospital of Xinxiang Medical College. The subjects in this study were divided into depression group and control group. The patients in depression group were hospitalized in the Second Affiliated Hospital of Xinxiang Medical College from September 2001 to December 2001. Inclusion International Classification of Diseases(10th edition) and Chinese Classifiliver function, electrocardiography and kidney function examination were quilizer or lithium salt were used in the past year; had the history of alcohol Had endocrine, heart, liver and kidney diseases and other serious somatic diseases. The 35 patients who met the above criteria were 14 males and 21females aged from 18 to 60 years with the average age of(36 ± 12) years in the depression group. In the control group there were 13 males and 17 females aged from 19 to 60 years with the average age of(34 ± 10)years.METHODS: The levels of plasma interleukin-2(IL-2) and solute interleukin-2 receptor(sIL-2R) were detected with enzyme-linked immunoadsorbent assay.disorder in patients with depression.RESULTS: The level of plasma IL-2 in the depression group(77.92± 36.85) pg/L was lower than that of the normal control group (98.98± 30. 72 ) pg/L( t = 2. 446, P ＜ 0.05). Moreover, IL-2 level was positively correlated to depth of sleep level( r = 0. 364, P ＜ 0. 05) . No significant difference in sIL-2R level was found between the two groups( P ＞ 0.05).CONCLUSION: The development of sleep disorder in patients with depression may be related with the level of cytokine, and the decrease of IL-2level can be the neurobiological basis of sleep level in depression.