ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure （ACLF） based on sarcopenia and other clinical indicators， and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital， Capital Medical University， from January 2019 to January 2022 were enrolled， and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group， CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra （L3）， and L3 skeletal muscle index （L3-SMI） was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors， and a nomogram was developed for presentation. The area under the ROC curve （AUC） was used to assess the predictive performance of the model， the calibration curve was used to assess the degree of calibration， and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia （hazard ratio ［HR］=1.962， 95% confidence interval ［CI］： 1.185‍ ‍—‍ ‍3.250， P=0.009）， total bilirubin （HR=1.003， 95%CI： 1.002‍ ‍—‍ ‍1.005， P<0.001）， international normalized ratio （HR=1.997， 95%CI： 1.674‍ ‍—‍ ‍2.382， P<0.001）， and lactic acid （HR=1.382， 95%CI： 1.170‍ ‍—‍ ‍1.632， P<0.001） were included in the sarcopenia-ACLF model. In the training cohort， the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF （0.80 vs 0.73， Z=1.97， P=0.049）. In the test cohort， the sarcopenia-ACLF model had a significantly larger AUC than MELD score （0.79 vs 0.69， Z=2.70， P=0.007） and MELD-Na score （0.79 vs 0.68， Z=2.92， P=0.004）. The calibration curve showed that the model had good calibration ability， with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities， the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients， which provides support for clinical decision-making and helps to optimize treatment strategies.

Objective:To analyze functional changes in macrophages in mouse models of vulvovaginal candidiasis (VVC) by modulating indoleamine 2,3-dioxygenase 1 (IDO1) .Methods:Forty specific-pathogen-free female ICR mice were randomly divided into 4 groups using a complete randomization method: a blank group, a VVC model group, a VVC model + 1-methyltryptophan (1-MT) group (referred to as the 1-MT group), a VVC model + interferon-γ (IFN-γ) group (referred to as the IFN-γ group), with 10 mice in each group. Except for the blank group, all the mice were injected subcutaneously with estradiol benzoate oil solution in the abdomen every other day for 6 days prior to modeling to induce pseudoestrus; after successful induction of pseudoestrus, the mice were inoculated vaginally with Candida albicans suspensions at a concentration of 2 × 10 9 CFU/ml once a day for 5 days to establish VVC mouse models, and subcutaneous injections of estradiol benzoate oil solution were continued simultaneously to maintain the pseudoestrus state; 1 day before inoculation with fungal suspensions, mice in the 1-MT group and IFN-γ group were pretreated with 1-MT and IFN-γ respectively, followed by once-daily same intervention for 6 consecutive days; mice in the blank group and VVC model group were intraperitoneally injected with physiological saline solution once a day for 6 consecutive days. On the 5th day of modeling, vaginal conditions in mice were observed and vaginal symptoms were scored; the vaginal lavage fluid was collected for smear microscopy and fungal colony counting; then, the mice were sacrificed, the vaginal tissues were collected and subjected to hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining, and the expression of IDO1 and the macrophage surface marker F4/80 was determined in the vaginal tissues by an immunofluorescence method; real-time fluorescence-based quantitative PCR (qPCR) was performed to determine mRNA expression levels of IDO1, inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1) in the vaginal tissues, and Western blot analysis to determine the IDO1 protein expression in the vaginal tissues. One-way analysis of variance was used to analyze the differences in indices among groups, and Tukey test was used for multiple comparisons. Results:Smear microscopic examination of the vaginal lavage fluid on the 5th day of modeling showed elongated hyphae with a few spores in the VVC model group, a large number of elongated hyphae aggregating in clusters with surrounding spores in the 1-MT group, and a few thin and short hyphae with a large number of spores in the IFN-γ group. Compared with the VVC model group (360.0 ± 15.9), the fungal colony counts in the vaginal lavage fluid significantly increased in the 1-MT group (523.7 ± 67.7, P = 0.002), but significantly decreased in the IFN-γ group (258.3 ± 27.57, P = 0.026). HE staining and PAS staining showed small abscess formation in the epidermis and predominant infiltration of neutrophils throughout the epidermal and dermal layers with a large number of spores and a few hyphae in the VVC model group; thickened epidermis and diffuse inflammatory infiltration predominated by neutrophils in the dermis were seen in the 1-MT group, with a large number of hyphae and spores aggregating into clusters, which were predominated by hyphae; in the IFN-γ group, spores aggregated in the epidermis without obvious hyphae, and a small amount of inflammatory cells predominated by neutrophils infiltrated the dermis. Immunofluorescence assay revealed that the relative fluorescence intensities of IDO1 and F4/80 were highest in the IFN-γ group and the 1-MT group, respectively. Western blot analysis revealed that the IDO1 protein expression in the VVC model group was significantly higher than that in the blank group ( P < 0.001) and the 1-MT group ( P < 0.05), but significantly lower than that in the IFN-γ group ( P < 0.05). qPCR showed that iNOS mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.01), and increased in the IFN-γ group compared with the blank group, VVC model group and 1-MT group (all P < 0.001); Arg-1 mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.001) and IFN-γ group ( P < 0.01), and increased in the 1-MT group compared with the blank group, VVC model group, and IFN-γ group (all P < 0.001) . Conclusion:In the VVC mouse models, upregulation of IDO1 may cause macrophage polarization toward the M1 phenotype, and inhibition of IDO1 may cause increased macrophage recruitment and exacerbate the inflammatory response.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.

ObjectiveTo investigate the characteristics of intrahepatic and extrahepatic organ failure at the onset of acute－on－chronic liver failure（ACLF）， to explore the features of a new clinical classification system of ACLF， and to provide a basis for the diagnosis， treatment， prognostic analysis of the disease. MethodsA retrospective analysis was performed for the clinical data of the patients who were hospitalized Beijing YouAn Hospital， Capital Medical University， from January 2015 to October 2022 and were diagnosed with ACLF for the first time. According to the conditions of intrahepatic and extrahepatic organ failure at disease onset， they were classified into type Ⅰ ACLF and type Ⅱ ACLF. Type Ⅰ ACLF referred to liver failure on the basis of chronic liver diseases， and type Ⅱ ACLF referred to acute decompensation of chronic liver diseases combined with multiple organ failure. The clinical features of patients with type Ⅰ or type Ⅱ ACLF were analyzed， and the receiver operating characteristic （ROC） curve was used to assess the value of MELD， MELD－Na， and CLIF－C ACLF scoring system in predicting the 90－day prognosis of ACLF patients with type Ⅰ or type Ⅱ ACLF. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank－sum test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsA total of 582 patients with ACLF were enrolled， among whom there were 535 patients with type Ⅰ ACLF and 47 patients with type Ⅱ ACLF. Hepatitis B and alcoholic liver disease were the main causes in both groups， with no significant difference between the two groups （P>0.05）. Chronic non－cirrhotic liver disease （28.2%） and compensated liver cirrhosis （56.8%） were the main underlying liver diseases in type Ⅰ ACLF， while compensated liver cirrhosis （34.0%） and decompensated liver cirrhosis （61.7%） were the main underlying liver diseases in type Ⅱ ACLF， and there was no significant difference in underlying liver diseases between the patients with type Ⅰ ACLF and those with type Ⅱ ACLF （P<0.001）. The patients with type Ⅱ ACLF had significantly higher median MELD score， MELD－Na score， and CLIF－C ACLF score than those with type Ⅰ ACLF （all P<0.001）. The patients with type Ⅱ ACLF had significantly higher 28－ and 90－day mortality rates than those with type Ⅰ ACLF （38.3%/53.2% vs 15.5%/27.5%， P<0.001）. For the patients with type Ⅰ ACLF who did not progress to multiple organ failure， the patients with an increase in MELD score accounted for 63.7% in the death group and 10.1% in the survival group （P<0.001）， while for the patients with type Ⅰ ACLF who progressed to multiple organ failure， there was no significant difference in the change in MELD score between the survival group and the death group （P>0.05）. In the patients with type Ⅰ ACLF， MELD score， MELD－Na score， and CLIF－C ACLF score had an area under the ROC curve （AUC） of 0.735， 0.737， and 0.740， respectively， with no significant difference between any two scores （all P>0.05）. In the patients with type Ⅱ ACLF， CLIF－C ACLF score had a significantly higher AUC than MELD score （0.880 vs 0.560， P<0.01） and MELD－Na score （0.880 vs 0.513， P<0.01）. ConclusionThere are differences in underlying liver diseases， clinical features， and prognosis between type Ⅰ and type Ⅱ ACLF， and different prognosis scoring systems have different emphases， which provide a basis for the new clinical classification system of ACLF from the perspective of evidence－based medicine.

Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Depressive Disorder, Major/metabolism* ; Basal Forebrain ; Depression ; Hippocampus/metabolism* ; Cholinergic Agents

Objective To investigate the CT and MRI manifestations of intra-abdominal aggressive fibromatosis and correlation with pathology.Methods The CT and MRI manifestations of 26 cases with intra-abdominal aggressive fibromatosis confirmed by pathological examination were analyzed retrospectively.Results 26 cases showed single solid mass,13 cases showed well-circumscribed and round-like,9 cases wrapped around the common bile duct,intestine or ureter,4 cases were lobulated which had unclear margin with surrounding tissues in pelvic.All the lesions displayed isodensity or slightly low density non-enhanced CT appearance,heterogenous high intensity FS T2WI,some larger tumors showed mixed signal.CT/MRI enhanced scan showed gradual enhancement in 26 cases.Conclusion Intra-abdominal aggressive fibromatosis have some certain imaging features,MRI can offer the histo logical features of tumors and have some correlation with pathology.

Objective: To analyze the residual risk of transfusion transmitted hepatitis B virus (HBV) infection by enzyme-linked immunosorbent assay (ELISA) method in hepatitis B surface antigen (HBsAg) negative blood donors, and to assess the infection status. Methods: A total of 45551 samples were collected from blood donors.All samples were tested by 2 different ELISA kids of HBsAg and nucleic acid testing (NAT) individually of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Those ELISA HBsAg negative and NAT single reactive (HBsAg-/HBV DNA+ ) specimens were analyzed by quantitative detection of HBV DNA and by serologic testing of HBV antigen and antibody. Results: A total of 44 HBsAg-/HBV DNA+ samples were detected, including 42 occult HBV infections (OBI) and 2 window period infections (WP). The detection rate of OBI rate was 0.90‰, and 32 samples of OBI sample HBV DNA was less than 20 IU/ml, and the OBI detection rate was significantly different between different genders, ages and blood donation times (P<0.05). In the OBI sample, there were 6 serological models, 92.9%(39/42) OBI samples hepatitis B core antibody (HBcAb) positive, and 76.9%(30/39) HBV DNA in HBcAb positive samples were less than 20 IU/ml; 29.5% (13/42) of OBI blood donors hepatitis B e antigen (HBeAb) and HBcAb were also positive, of whom 84.6% (11/13) were HBV DNA quantitatively <20 IU/ml. Conclusions HBV residual risk of transfusion-transmitted infection may occur through HBsAg- and single NAT reactive blood donors, mainly include OBI, and HBV DNA low level. Blocking of single NAT reactive blood donors could reduce transfusion-transmitted HBV infection.

Objective To investigate the clinical efficacy and safety of transcatheter arterial chemoemblization (TACE) using raltitrexed and lobaplatin in treating advanced hepatocellular carcinoma (HCC).Methods From March 2009 to November 2014,95 cases were treated by raltitrexed combined with lobaplatin (raltitrexed group) through TACE and 124 cases by fluorouracil combined with oxaliplatin (fluorouracil group) through TACE.Disease control rate (DCR),median progression-free survival (mPFS) time and median overall survival (mOS) time were compared between the two groups.Survival rate were analyzed using Kaplan-Meier method and Log-rank analysis in SPSS 16.0.Results The disease control rate of raltitrexed group was 91.6％ (87/95),compared with fluorouracil group of 84.6％ (105/124) in fluorouracil group (x2 =2.505,P =0.474).The mPFS of raltitrexed group was 6.8 months and that of fluorouracil group was 5.9 months (x2 =5.542,P =0.019);mOS of raltitrexed group was 13.6 months and fluorouracil group was 11.4 months (x2 =5.953,P =0.015).The main adverse reactions in the two groups were not statistically significant (P ＞ 0.05).Conclusions TACE using rahitrexed and oxaliplatin prolongs the progression free survival and overall survival time of patients with advanced hepatic carcinoma.

Objective To compare the differences of two kinds of EIA reagents for HIV-1/2 (Ab/Ag) screening results of voluntary blood donors,in addition to find out the feasibility of reducing 1 times of EIA detection.Methods To collect data of HIV 1/2 screening positive results and confirmatory test for voluntary blood donors from 2009 to 2014 in Jiaxing area,and to compare the relationship of screeing test results with that of the confirmatory test,and then to analyze the relevance between S/CO values of screening test and confirmatory test.Results Screening positive rates of domestic and imported reagents,which were 9.58/10 000 and 12.43/10 000,respectively;and the confirmatory coincidence rates were 11.84％ and 9.12％,respectively.There was no significant difference (x2 =1.11,P＞0.05).The double-reagent joint detection positive rate was 1.37/10 000,and its positive predictive value was 82.86％.Single-reagent test result compared with that of double-reagent test,which had significant differences (x2domestic =94.04,P＜0.05 and x2ximported =124.86,P＜0.05).When the S/CO value was more than 6,domestic and imported reagents positive predictive values were 93.55％ (29/31) and 87.50％ (28/32),respectively.Conclusion There is no difference between domestic and imported reagents EIA-HIV1/2.

Objective To research and analyze serological and virological epidemiology charactererization of occult hepatitis B virus infection in Jiaxing volunteer blood donors.Methods 52 698 samples were screened by ELISA(HBsAg、antiHCV 、anti-HIV、anti-TP) and Nucleic acid amplification technique(NAT),then NAT positive samples were further identified to detect virus type.HBsAg-/HBV-DNA+ samples were collected in three different kinds of qualitative HBsAg detection of ELISA kit.The quantitative determination of HBsAg and anti-HBs were used by chemiluminescencemethod.At the same time,real-time fluorescence quantitative PCR (QPCR) was used to measure the viral load of HBV.Further analysis and study on the serological and virological distribution of OBI combined with five markers of hepatitis B virus (HBV),with tracing general epidemiological data (sex,age and age).Results The prevalence rate of OBI was 0.89‰ (1 ∶ 1 121) in all donors with OBI infection,and 2 cases of window period (WP) were found in 52698 donors (1 ∶ 26 349).The results of HBsAg and HBeAg were negative in 49 HBsAg-/HBV-DNA+ samples,and 6OBI serological profiles were found.Anti-HBs quantitative concentration(＞100 mIU/mL)accounted for 27.66％ (13/47),while anti-HBc+ positive rate was 91.49％ (43/47).HBV-DNA nucleic acid quantitative ranged from 4.10 to 1.82× 103(IU/mL) (median of 15.83),whereas HBsAg+/HBV-DNA+positive viral load was in the range of 61.47 to 1.28× 104(IU/mL) (median of 538.15).The difference was significant in viral load between experiment group and control group(P＜0.05).Male donors of more than 40 years were higher in prevalence rate of OBI infection (P＜0.05),meanwhile there was a significant difference in OBI infection rate between repeated blood donors and fnrst blood donors(0.01＜P＜0.05).Conclusion The viral load was low in OBI infected donors,and anti-HBc+ was the main manifestation.NAT had the ability to detect OBI,shorten the window period,and contributed to ensure the safety of clinical blood.