AIM: To evaluate the expression of tumor necrosis factor-α(TNF-α)in the iris and ciliary body of Wistar rats in the endotoxin-induced uveitis(EIU), and the effect of Xuebijing injection on its expression.METHODS:A total of 65 Wistar rats were randomly divided into three groups: Group A(normal saline, n=5), Group B(normal saline+endotoxin-injected, n=30), and Group C(Xuebijing+endotoxin-injected, n=30). The EIU model was induced in Wistar rats of the groups B and C by injecting LPS into the plantar surfaces of the hind feet, and normal saline(15 mL/kg)or Xuebijing(15 mL/kg)were intraperitoneally administered 30 min before LPS administration. The rats of the groups B and C were further divided into 6 subgroups after LPS injection, including 6, 12, 18, 24, 48, and 72 h subgroups, with 5 rats in each group. Furthermore, the intraocular inflammation of the rats was observed at each time above, the number of infiltrating cells in the aqueous humor was counted, and the pathological changes were observed in the iris and ciliary body of rats using hematoxylin and eosin(HE)staining. TNF-α expression in iris and ciliary tissue at different postoperative time points was evaluated using immunohistochemistry.RESULTS: Clinical observations indicated no signs of uveitis in the group A, signs of uveitis were observed in the group B. Both iris symptoms and damage were significantly reduced in the group C compared to the group B(P<0.01). Cell counts in the aqueous humor revealed no inflammatory cells in the group A, while the number of aqueous humor cells in the group C was significantly reduced compared to Group B(P<0.01). HE staining revealed no cellular infiltration in the group A. In the group B, some cellular infiltration was observed in the eyes at 6 h post-LPS exposure. The number of infiltrating cells increased over time, peaked at 24 h, and gradually declined thereafter. In the group C, cell infiltration was not obvious at 6 h, few at 24 h, and nearly disappeared by 48 h. Immunohistochemical staining showed higher TNF-α expression in the ciliary body and iris in the group B than in the group A(P<0.01). Compared to the group C, TNF-α expression in the group B was significantly upregulated following LPS injection(P<0.01).CONCLUSION:TNF-α expression was elevated in EIU rats, and there was a positive correlation between its mean optical density ratio and inflammation degree. Moreover, Xuebijing injection could alleviate inflammation response through the reduction of TNF-α levels.

ObjectiveTo investigate the effect of kinesin family member 15 （KIF15） on the proliferation of hepatocellular carcinoma （HCC） cells and its mechanism of action. MethodsTCGA and GEPIA datasets were analyzed to determine the expression of KIF15 in HCC and its effect on tumor stage and survival. Quantitative real-time PCR and Western blot were used to measure the expression level of KIF15 in human-derived HCC cell lines （HepG2， Hep3B， MHCC-97H， and LM3） and human normal liver cell line L02 cultured in vitro， and Hep3B and HepG2 were selected for subsequent studies. CCK-8 assay， plate colony formation assay， and EdU staining were performed for Hep3B cells transfected with shRNA-NC or shRNA-KIF15 and HepG2 cells transfected with LV-vector or LV-KIF15 to evaluate the viability and proliferative capacity of these cells. GSEA was used to analyze the potential signaling pathways associated with KIF15 in HCC， and Western blot was used for detection. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe analysis of TCGA and GEPIA datasets showed that in HCC patients， the expression of KIF15 in HCC tissue was significantly higher than that in normal tissue， and the HCC patients with high KIF15 expression tended to have a poorer prognosis. Compared with sh-NC-Hep3B， sh3-Hep3B showed significant reductions in the mRNA and protein levels of KIF15 （P<0.05）， cell viability， clone formation number， and EdU positive rate （all P<0.05）. Compared with vector-HepG2， LV-KIF15-HepG2 showed significant increases in the mRNA and protein levels of KIF15 （P<0.05）， cell viability， clone formation number， and EdU positive rate （all P<0.05）. Subcutaneous tumor assay showed that compared with sh-NC-Hep3B， sh3-Hep3B showed reductions in tumor volume and tumor weight， as well as a significant reduction in the immunohistochemical score of Ki67 and a significant increase in the immunohistochemical score of TUNEL （P<0.05）. GSEA analysis showed that the PI3K/AKT/mTOR pathway was positively correlated with KIF15 in HCC （NES=1.59， P<0.001）. Western blot showed that LY294002 could inhibit the PI3K/AKT/mTOR pathway upregulated in LV-KIF15-HepG2， and compared with LV-KIF15-HepG2， LY294002+LV-KIF15-HepG2 showed significant reductions in cell viability， clone formation number， and EdU positive rate （all P<0.05）. ConclusionKIF15 enhances the viability and proliferative capacity of HCC cells by upregulating the PI3K/AKT/mTOR signaling pathway.

Objective To investigate the feasibility of constructing a preeclampsia(PE)risk model based on multiple exosomal micrornas(miRNA)expression levels and to verify its efficacy in predicting PE.Methods A total of 1037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects.The expression of exosomal miRNA(including miR-155-5p,miR-215-5p,miR-203a-3p,miR-199a-5p and miR-125a-3p)in all samples was detected by qRT-PCR.Then,all patients were followed up to the end of pregnancy.The occurrence of PE during the follow-up period was counted,and all samples were divided into the PE group and the control group according to results.Cox regression was used to analyze the influencing factors of PE.The multi-miRNA risk model was constructed with ggrisk package,and the predictive effect of the model on PE was evaluated by receiver operating characteristic(ROC)curve.Results By the end of follow-up on October 31,2022,974 cases were finally followed up,and the follow-up completion rate was 93.92%.Among all the 974 patients who completed the follow-up,65 patients developed PE,so they were finally divided into the PE group,and 909 cases were used as the control group.The age,pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group(P＜0.05).The proportions of smoking history and drinking history were higher in the PE group than those of the control group(P＜0.05).The contents of triglyceride(TG),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),alanyl aminotransferase(ALT),aspartate aminotransferase(AST),platelet distribution width(PDW),mean platelet volume(MPV),miR-155-5p,miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group,while contents of thyroid stimulating hormone(TSH),miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group(P＜0.05).The expression levels of miR-125a-3p,miR-155-5p,miR-199a-5p and miR-215-5p were independent predictors of PE(P＜0.05).The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE(AUC=0.998),with a sensitivity of 98.46%(63/65)and a specificity of 93.94%(854/909).Conclusion miR-125a-3p,miR-155-5p,miR-199a-5p,miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE,and the PE prediction model constructed with the above five miRNAs has better effect.

BACKGROUND:Olfactory dysfunction is an early biological marker of various diseases.However,the neuroimaging mechanism by which olfactory dysfunction occurs following cerebral small vessel disease is unclear. OBJECTIVE:To explore the different neuroimaging mechanisms of olfactory function regulation in patients with cerebral small vessel disease and Parkinson's disease,and explore the potential application value of olfactory function assessment in patients with cerebral small vessel disease. METHODS:Neuropsychological and olfactory tests,high-resolution structural magnetic resonance and resting-state functional magnetic resonance data were collected in 80 patients with cerebral small vessel disease,44 healthy controls and 29 patients with Parkinson's disease.DPABI,SPM12 and SPSS were used to analyze and compare the amplitude of low frequency fluctuation,regional homogeneity and functional connectivity values between the cerebral small vessel disease,control and Parkinson's disease groups.Correlations between the significantly altered resting-state functional magnetic resonance imaging measures and olfactory and cognitive scores were evaluated. RESULTS AND CONCLUSION:Compared with the control group,low-frequency fluctuation amplitude of the right dorsolateral superior frontal gyrus and the regional homogeneity of the left wedge leaf were significantly reduced in the cerebral small vessel disease and Parkinson's disease groups.The right dorsolateral superior frontal gyrus and the left cuneiform lobe are the seed points.Compared with the Parkinson's disease group,the functional connectivity values of the right anterior cunei,inferior temporal gyrus,anterior central gyrus and dorsolateral superior frontal gyrus,left posterior central gyrus and inferior temporal gyrus were significantly enhanced in the control and cerebral small vessel disease groups.The left cuneiform lobe was the seed point.Compared with the control group,the functional connectivity of the left lingual gyrus was significantly weakened in the cerebral small vessel disease and Parkinson's disease groups.The functional connectivity values of the left middle temporal gyrus and the right posterior central gyrus were enhanced in the control group compared with the cerebral small vessel disease and Parkinson's disease group,and that was enhanced in the cerebral small vessel disease group compared with the Parkinson's disease group.Correlation analysis showed that the olfactory score and cognitive score were positively correlated in the cerebral small vessel disease group,and the regional homogeneity of the left wedge lobe was negatively correlated with the Montreal Cognitive Assessment Scale score,while the functional connectivity of left wedge lobe-left middle temporal gyrus in the Parkinson's disease group was positively correlated with the olfactory recognition score,and the functional connectivity values of the left wedge lobe-left posterior central gyrus and left wedge lobe-left lingual gyrus were positively correlated with the olfactory identification score and the total olfactory score,respectively.The regulation of olfactory function in patients with cerebral small vessel disease has a different neuroimaging mechanism from that of olfactory dysfunction in patients with Parkinson's disease.The olfactory function of patients with cerebral small vessel disease is related to cognitive function.It is speculated that the olfactory function following cerebral small vessel disease is a secondary change of brain dysfunction,while olfactory dysfunction following Parkinson's disease is directly caused by abnormal function of olfactory-related brain areas.Olfactory function assessment in patients with cerebral small vessel disease has potential application in predicting cognitive function.

Since there is a lack of obvious clinical symptoms in the early stage of hepatocellular carcinoma (HCC), most patients have progressed to the advanced stage at the time of confirmed diagnosis. There are limited treatment options for HCC patients who miss the opportunity for surgery, so it is of great importance to find new therapeutic targets. Tumor-associated macrophages (TAMs) are a group of macrophages existing in the tumor immune microenvironment and affect the malignant behaviors of HCC cells and the state of immune escape within the tumor. This article introduces the origin and classification of TAM, summarizes the role and mechanism of TAMs in vascular proliferation, invasion and metastasis, formation and maintenance of stemness, and anti-tumor immunity in HCC, and briefly describes the current research advances in therapeutic targets for TAM, and it is pointed out that targeting TAM may be a promising direction for clinical treatment.

Abstract Psychological stress and coping strategies are important factors affecting physical and mental health. Unhealthy eating behavior caused by stress is common in children and adolescents, which has not been fully clarified. In this paper, studies on the association of psychological stress with general eating behavior, abnormal eating behavior or eating disorders among children and adolescents were reviewed. The epidemiology and influencing factors were elaborated, and the possible physiological mechanism was summarized, in order to provide reference for the future research.

Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

ObjectiveTo investigate the clinical features of patients with Caroli disease. MethodsThe clinical data were collected from 41 patients who were diagnosed with Caroli disease in The Fifth Medical Center of Chinese PLA General Hospital from April 2015 to January 2020, and the patients were divided into type I group with 16 patients and type Ⅱ group with 25 patients. A retrospective analysis was performed for general information, laboratory markers, and clinical features. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data; a Spearman correlation analysis was also performed. ResultsThe type Ⅰ group had a significantly higher level of albumin (Alb) than the type Ⅱ group (t=0.976, P=0.048), and the type Ⅱ group had a significantly higher prothrombin time (PT) than the type I group (Z=3.115, P=0.001). Compared with the type I group, the type Ⅱ group had significantly higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (χ2=6.077, 5.468, and 2.403, P=0.002, 0.019, and 0.028). In the patients with type Ⅱ Caroli disease, the level of cholinesterase was negatively correlated with the incidence rates of esophageal and gastric varices and portal hypertension (r=-0.468 and -0.436, P=0.018 and 0.029); Alb level was negatively correlated with the incidence rate of esophageal and gastric varices (r=-0.561, P=0.004); red blood cell count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.662, -0.566, and -0.436, P＜0.001, P=0.003, and P=0.029); hemoglobin count was negatively correlated with the incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension (r=-0.605, -0.590, and -0.510, P=0.001, 0.002, and 0.009); PT was positively correlated with the incidence rates of esophageal varices and portal hypertension (r=0.488 and 0.520, P=0.013 and 0.008). ConclusionCompared with the patients with type I Caroli disease, the patients with type Ⅱ Caroli disease have a higher incidence rates of esophageal and gastric varices, upper gastrointestinal bleeding and/or tarry stool, and portal hypertension, with the changes in clinical indicators such as the decrease of Alb level and the increase of PT level, and they tend to have poor prognosis.

A 49-year-old woman was admitted to hospital with intermittent dizziness and fatigue for 7 years. The symptoms were aggravated and accompanied by bone pain for more than 4 months. She was referred to our hospital. Laboratory tests and imaging findings suggested that acquired Fanconi Syndrome (FS) was associated with smoldering multiple myeloma (MM). Renal biopsy and electron microscopy confirmed the diagnosis of proximal light chain tubular disease (LCPT). LCPT causes proximal tubular dysfunction, which is characterized by the cytoplasmic crystal deposition usually kappa monoclonal light chain in the proximal tubule. MM with FS and LCPT is less common in clinical practice because it is difficult to diagnose. This is a typical case focusing on the differential diagnosis of monoclonal gammopathy of renal significance(MGRS) such as LCPT and plasma cells diseases.