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.

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 explore the effeet of Zizyphus jujubekernelfreeze - dried powder on sleep and wakefulness and energy metabolism rate in rats under 24 h eontinuous darkness and its mechanism. Method U- sing the eortieal eleetroeneephalography method and the experimental animal monitoring system (CLAMS) and taking the time of wakefulness and sleep as well as the number of activities, food intake, and caloric pro- duetion as indicators to explore the funetion of it on improving energy metabolism rate. Theenzyme - linked immunoassay was used to determine the changes in the eontent of LEP, POMC, and NPY involved in energy regulation in the hypothalamus, so as to study the energy change mechanism of it. Result Compared with the DD group, the MAT group had redueed daytime awakening time, increased sleep time, deereased aetivities, no signifieant differenee in food intake, and inereased caloric production. There was no significant difference in night awakening and sleep time, no significant difference in the number of activities, reduced food intake , and increased caloric production. The weight gain of rats decreased; Compared with the DD group, the LEP content in the hypothalamus of the MAT group increased, the POMC content increased and the NPY content decreased. Conclusion By increasing LEP, POMC content and decreasing NPY content in hypothalamus , Zizyphus jujubekemelfreeze - dried powder collected the disturbance of sleep and wakefulness state and abnormal energy metabolism rate of rats caused by 24 h continuous dark condition.

Objective To observe the clinical efficacy and safety of icotinib tablets in the treatment of stage Ⅲ A-N2 non-small cell lung cancer (NSCLC).Methods A total of 56 patients with stage ⅢA-N2 NSCLC were randomly divided into control group and treatment group with 28 cases per group.The control group was treated with 60-75 mg · m-2 docetaxel,once a week,intravenous drip,or 500 mg · m pemetrexed,once every 3 weeks,intravenous drip,discontinuation of treatment when the disease progresses or adverse drug reactions cannot be tolerated.The treatment group was treated with icotinib tablets 125 mg,tid,orally,discontinuation of treatment when the disease progresses or adverse drug reactions cannot be tolerated.The clinical efficacy,peripheral blood dendritic cell subsets,and adverse drug reactions were compared between two groups.Results After treatment,the objective remission rates of the treatment group and the control group were 89.29％ (25 cases/28 cases) and 71.43％ (22 cases/28 cases),the difference was statistically significant (P ＜ 0.05).After treatment,the number of dendritic cells (DC) in the treatment group and the control group were (15.44 ± 2.08) and (12.83 ± 1.71) × 106/L,the ratio of dendritic cells to mononuclear cells (DC/PBMC) were (0.62 ± 0.08) ％ and (0.57 ± 0.07) ％,the differences were statistically significant (P ＜ 0.05).The adverse drug reactions of two groups were rashes,diarrhea and mild liver dysfunction.The total incidences of adverse drug reactions in the treatment group and the control group were 46.43％ and 42.86％ without significant difference (P ＞ 0.05).Conclusion The clinical efficacy of icotinib tablets in the treatment of stage ⅢA-N2 NSCLC was exact,and it did not increase the incidence of adverse drug reactions.

Objective To develop the finite element model of six-year-old child occupant lower extremity with higher biofidelity and validate the model of knee joints, as well as analyze the biomechanical responses of growth plate under frontal impact load and injury mechanisms of the knee joint by using this model. Methods The six-year-old child occupant lower extremity with growth plate was modeled based on children’s anatomy and CT images, and corresponding material properties of the lower extremity model were assigned．The model was validated according to biomechanical experiments by Kerrigan et al. and Haut et al. and then was used to analyze the injury results of growth plate with different material properties. Results The model validation was qualified by comparing the curves from the experimental and simulation results．The growth plates at knee regions could change injury patterns of the child occupant lower extremity fracture. The material properties of growth plate could affect threshold of axial damage of the femur as well as relative position of the fracture． Conclusions The validated model can be used for related study and application on biomechanical responses and injury mechanisms of six-year-old child occupant lower extremities．

Objective To explore the brain injury mechanism and enrich the database of human finite element (FE) biomechanical model by developing the FE model of one-year-old toddler head. Methods Based on CT data from Chinese one-year-old toddler head with substantial and detailed information, the head model with detailed anatomical structure was constructed by using the medical software Mimics to get the head geometry data, as well as the reverse engineering software to divide NURBS surface and build the geometric model. Finally, the FE pre-processing software was used mesh the model. The FE model of one-year-old toddle head was validated by data from anatomic and cadaver experiments, and was used for preliminary analysis on damage mechanism of one-year-old toddler head. Results The FE model of Chinese one-year-old male toddler head was developed, which included and distinguished the gray matter and white matter of brain and cerebellum, hippocampus, fontanel, sagittal suture, coronal suture, brainstem and ventricles. The cadaver head static compression experiments and drop experiments were reconstructed by using this head model, and the results showed that the FE model of head had similar mechanical properties with the cadaver, which proved the validity of the FE model. Simulation results showed that skull stiffness and skull injury severity varied with different compression rates. Conclusions The FE model of one-year-old toddler head with detailed anatomical structures is of great biofidelity. The FE head model can be used to further investigate the detailed injury mechanism of deep brain tissues, especially for the closed craniocerebral injury, which provides an effective way and tool for the related research and clinical application.

Objective To develop the finite element model of six-year-old child occupant lower extremity with higher biofidelity and validate the model of knee joints,as well as analyze the biomechanical responses of growth plate under frontal impact load and injury mechanisms of the knee joint by using this model.Methods The sixyear-old child occupant lower extremity with growth plate was modeled based on children's anatomy and CT images,and corresponding material properties of the lower extremity model were assigned.The model was validated according to biomechanical experiments by Kerrigan et aL and Haut et aL and then was used to analyze the injury results of growth plate with different material properties.Results The model validation was qualified by comparing the curves from the experimental and simulation results.The growth plates at knee regions could change injury patterns of the child occupant lower extremity fracture.The material properties of growth plate could affect threshold of axial damage of the femur as well as relative position of the fracture.Conclusions The validated model can be used for related study and application on biomechanical responses and injury mechanisms of sixyear-old child occupant lower extremities.

Objective To predict biomechanical responses of neck injuries under different loading conditions based on the finite element model of the 6-year-old pediatric neck. Methods The finite element model of the 6-year-old pediatric neck with real anatomical structural muscles was developed, according to the CT images. The model was verified by reconstructing the dynamic tensile test of different cervical spine segments, the tensile test of full cervical spine and the low speed impact experiment of the pediatric volunteers. Results The force-displacement curves, obtained from the simulations on tensile test of different cervical spine segments and tensile test of full cervical spine, were in good agreement with the experimental curves. The head angular velocity-time curve obtained from simulations on pediatric volunteer was consistent with the corridor obtained from experimental data. Conclusions The model is validated and can be used for studying the biomechanical responses and injury mechanism of pediatric neck under different loading conditions.

To explore the genetic characteristics of viral quasispecies in HIV-1 CRF07_BC infections among intravenous drug users (IDU), the gp120 fragments of HIV-1 env gene were amplified from plasma samples collected from 6 CRF07_BC infected persons using single genome amplification and sequencing (SGA/ SGS) method, and 11 to 28 sequences were obtained from these samples, respectively, A neighbor-joining phylogenetic tree was reconstructed to describe the genetic characteristics of viral quasispecies. The Simplot, segments' phylogenetic trees and diversity plots based on average pairwise distance (APD) were used to identify the recombination events between quasispecies. The SGA sequences derived from single specimen formed a large monophyletic cluster in the neighbor-joining phylogenetic tree and showed the complex topologic structures of viral quasispecies. Of the 6 CRF07_BC infected patients, only one possessed the high genetic homogeneity, whereas the other five individuals showed high heterogeneity, with two to four subclusters inside the monophyletic cluster for each specimen. In addition, the recombinant events were identified among viral quasispecies from 3 cases. The results show SGA technique and phylogenetic analyses are useful tool to investigate the intrahost CRF07_BC gp120 complex quasispecies variation and high genetic diversity.
Adult ; Drug Users ; Female ; HIV Infections ; virology ; HIV-1 ; classification ; genetics ; isolation & purification ; Humans ; Male ; Molecular Sequence Data ; Phylogeny ; Substance Abuse, Intravenous ; virology ; Young Adult