ObjectiveTo investigate whether paeonol exerts a protective effect on mice with alcoholic liver injury by regulating the takeda G-protein-coupled receptor 5 （TGR5）/protein kinase A （PKA）/cAMP response binding element （CREB） signaling pathway mediated by Eubacterium. MethodC57BL/6 mice were randomly divided into five groups： normal group， model group， paeonol group （480 mg·kg^-1）， antibiotic group （Abs group）， and antibiotic + paeonol group. Lieber-DeCarli liquid was used to feed C57BL/6 mice on the second day of modeling for 10 days. The blood lipids， liver function， inflammatory factors， and oxidative stress levels in mice were measured. Hematoxylin-eosin staining （HE） and oil red O staining were used to observe the morphological changes and fat accumulation in liver tissue. 16S rDNA sequencing was used to detect the diversity of intestinal microbiota in the blank， model， and paeanol groups. Western blot was used to detect the effect of paeonol on the expression levels of protein related to the signaling pathway of atresia band protein 1 （ZO-1）， Claudin-1， and TGR5/PKA/CREB in mouse ileal tissue. ResultCompared with those in the blank group， the blood lipids， liver function， oxidative stress levels， and the expression of inflammatory factors in the model group increased （P<0.01）， and the liver fat vacuoles were obvious. The ileal mucosa was seriously damaged， and the protein contents of ZO-1， Claudin-1， and TGR5/PKA/CREB in the ileal tissue decreased significantly （P<0.01）. The intestinal microbiota changed， and the proteobacteria phylum increased significantly. The ratio of Bacteroidetes to Firmicutes decreased. The relative abundance of Dubosiella newyorkensis， Lactobacillus， Bifidobacterium， and other genera decreased， while the relative abundance of Escherichia-Shigella， Morganella， Providencia， and Proteus increased significantly. Compared with the model group， paeonol significantly reduced the blood lipids， liver function， oxidative stress levels， and expression of inflammatory factors in mice with alcohol diet-induced liver injury （P<0.05）， decreased liver fat vacuoles， improved and restored the ileal intestinal barrier， and restored the normal structure of hepatocytes and ileal cells. The intestinal microbiota disorder caused by alcohol was improved， and the relative abundance of beneficial bacteria such as Eubacterium spp. was increased. The protein expression levels of ZO-1， Claudin-1， and TGR5/PKA/CREB in ileal tissue were increased （P<0.05）. ConclusionPaeonol has a protective effect on alcoholic liver injury in mice， and the mechanism of action is achieved by regulating the Eubacterium-mediated TGR5/PKA/CREB signaling pathway to ensure anti-inflammatory effect and improve the intestinal barrier.

Objective To observe the protective effect of modified Baishile Decoction on hippocampal neuronal cells cultured in vitro;To explore its mechanism of treating post-stroke depression.Methods Hippocampal neuronal cells from mammary rats were isolated and cultured in vitro,cell injury was induced by oxygen glucose deprivation combined with lipopolysaccharide.The cells were divided into normal group,model group,blank serum group(10%)and modified Baishile Decoction containing serum group(10%).Invertedmicroscope was used to observe cell morphological changes,CCK-8 method was used to detect cell survival rate,Hoechst33342 staining was used to observe apoptosis,ELISA was used to detect Glu,5-HT,TNF-α,IL-1β,and IL-6 contents in cell supernatant,the expressions of purinergic P2X7 receptor(P2X7R)and NOD-like receptor protein 3(NLRP3)were detected by immunofluorescence staining.Results Compared with the normal group,the hippocampal neurons in the model group showed significant changes in cell morphology,the cell survival rate significantly decreased(P<0.01),the cell apoptosis increased(P<0.01);Glu,TNF-α,IL-1β,IL-6 contents in cell supernatant significantly increased(P<0.05,P<0.01),5-HT content significantly decreased(P<0.01),P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly increased(P<0.01).Compared with the model group,the morphology of hippocampal neurons in modified Baishile Decoction containing serum group was significantly improved,the cell survival rate significantly increased(P<0.01),the cell apoptosis reduced(P<0.01);Glu,TNF-α and IL-1β content in cell supernatant significantly reduced(P<0.05,P<0.01),5-HT content significantly increased(P<0.01),and P2X7R and NLRP3 expressions in hippocampal neuronal cells significantly decreased(P<0.01).Conclusion Modified Baishile Decoction may exert a protective effect on oxidative glucose deprivation combined with lipopolysaccharide induced hippocampal neuronal inflammation damage by inhibiting the P2X7R/NLRP3 signaling pathway,regulating neurotransmitter secretion,and inhibiting inflammatory factor release,thus treating post-stroke depression.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

Primary sarcopenia is age-related and can lead to falls, osteoporosis, fractures, malnutrition, frailty, sarcopenic obesity, and even loss of independent living silks in patients, which all increase the risk of hospitalization and the cost of healthcare.Early diagnosis of sarcopenia is an effective means to prevent these adverse events.This paper reviewed relevant studies conducted in China and other countries on imaging techniques for the diagnosis of sarcopenia, and examines the advantages and disadvantages of different techniques, in order to sort out well-grounded principles for clinical practice and future improvement in the management of sarcopenia.

To address the issue of weight gain and abnormal lipid metabolism caused by clozapine and olanzapine administration in patients with schizophrenia， a qualitative and systematic review was carried out， thus providing references for clinical treatment and future research. This review embraces the aspects of pharmacotherapy， traditional Chinese medicine treatment and so on.

PURPOSE: This study aimed to evaluate the prognostic impact of lymphovascular invasion (LVI) in patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We collected data from 180 patients who were treated with RNU from 2005 to 2013 at our institution. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses. RESULTS: LVI was present in 28 patients (15.6%), which was associated with higher pathological tumor stage (p < 0.001), tumor necrosis (p=0.012), lymph node metastasis (p=0.017) and multifocality (p=0.012). On multivariate analysis, LVI was an independent prognostic factor of recurrence-free survival [RFS: hazard ratio (HR)=2.954; 95% confidence interval (CI)=1.539–5.671; p=0.001] and cancer-specific survival (CSS: HR=3.530; 95% CI=1.701–7.325; p=0.001) in all patients. In patients with node-negative UTUC, LVI was also a significant predictor of RFS (HR=3.732; 95% CI 1.866–7.464; p < 0.001) and CSS (HR=3.825; 95% CI=1.777–8.234; p=0.001). CONCLUSION: LVI status was an independent predictor in patients with UTUC who underwent RNU. The estimate of LVI could help physicians identify high-risk patients and make a better medication regimen of adjuvant chemotherapy.
Carcinoma, Transitional Cell ; Chemotherapy, Adjuvant ; Humans ; Lymph Nodes ; Methods ; Multivariate Analysis ; Necrosis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prognosis ; Urinary Tract

Objective: To investigate the clinical and pathologic features, diagnosis and differential diagnosis of hypertrophic port-wine stain (PWS). Methods: Cases of hypertrophic PWS, collected from Henan Provincial People′s Hospital between 2012 and 2018, were retrospectively analyzed for their clinical and pathologic features, immunophenotype and histochemical data, and the relevant literature was reviewed. Results: Twenty-four cases of PWS were included in this cohort, located in the head and neck region (20 cases), limbs (2 cases), and trunk (2 cases). The clinical presentations were mainly red or purple-red plaques or slow growing, painless nodules, or thickened and raised above the skin surface. Microscopically, deformed blood vessels showed honeycomb-like, plexiform or cluster-like growth pattern, and diffusely involved the dermis, skin appendages, subcutaneous fat tissue, and deep skeletal muscles; The vascular lumen of the deformed vessels was dilated (≥100 μm in diameter), and in 18 cases the lumen was greater than 400 μm. The superficial dermis mainly contained few deformed capillaries. The deep wall showed thickening of blood vessel wall and fibrous tissue hyperplasia. Elastic fiber and Masson staining indicated abnormal venous vessel, which in some cases contained small amount of abnormal arterioid vessel,without vascular endothelial cell proliferation in all cases. In 24 cases, 19 cases had epidermal atrophy, 6 with vascular chronic inflammation or epidermal ulcer, 4 with capillary hemangioma, 4 with sebaceous gland hyperplasia, 2 with epidermal papillary hyperplasia and 2 with vascular keratomas. Conclusions PWS is a common congenital capillary malformation. The number of histologically deformed capillaries is reduced and they usually locate in the superficial part. The deep vascular wall is increased with thick venous malformation, diffusely involving the dermis and deep skeletal muscle. Furthermore, PWS needs to be differentiated from infantile hemangioma, cavernous hemangioma and vascular keratomas.

investigate the clinical and pathologic features, diagnosis and differential diagnosis of hypertrophic port?wine stain (PWS). Methods Cases of hypertrophic PWS, collected from Henan Provincial People′s Hospital between 2012 and 2018, were retrospectively analyzed for their clinical and pathologic features, immunophenotype and histochemical data, and the relevant literature was reviewed. Results Twenty?four cases of PWS were included in this cohort, located in the head and neck region (20 cases), limbs (2 cases), and trunk (2 cases). The clinical presentations were mainly red or purple?red plaques or slow growing, painless nodules, or thickened and raised above the skin surface. Microscopically, deformed blood vessels showed honeycomb?like, plexiform or cluster?like growth pattern, and diffusely involved the dermis, skin appendages, subcutaneous fat tissue, and deep skeletal muscles; The vascular lumen of the deformed vessels was dilated (≥100 μm in diameter), and in 18 cases the lumen was greater than 400 μm. The superficial dermis mainly contained few deformed capillaries. The deep wall showed thickening of blood vessel wall and fibrous tissue hyperplasia. Elastic fiber and Masson staining indicated abnormal venous vessel, which in some cases contained small amount of abnormal arterioid vessel, without vascular endothelial cell proliferation in all cases. In 24 cases, 19 cases had epidermal atrophy, 6 with vascular chronic inflammation or epidermal ulcer, 4 with capillary hemangioma, 4 with sebaceous gland hyperplasia, 2 with epidermal papillary hyperplasia and 2 with vascular keratomas. Conclusions PWS is a common congenital capillary malformation. The number of histologically deformed capillaries is reduced and they usually locate in the superficial part. The deep vascular wall is increased with thick venous malformation, diffusely involving the dermis and deep skeletal muscle. Furthermore, PWS needs to be differentiated from infantile hemangioma, cavernous hemangioma and vascular keratomas.

Objective To investigate the basic clinical features in 371 cases of colorectal polyps and its relationship with fecal occult blood and carcinoembryonic antigen(CEA).Methods The retrospective analysis was performed on 371 inpatients with colo-rectal polyps.The relationship among gender,number of polyps and polyps anatomical site in different ages of patients was investi-gated,and the relationship between fecal occult blood and CEA with polyp canceration was analyzed by 1.5?3.0 years follow-up. Results Among 371 cases of colorectal polyps,the female patients were gradually increased and single polyp was gradually de-creased along with the age increase;due to different ages,there was the statistically significant difference in the polyp locations (χ2 =9.759,P=0.045);the distribution difference of the patients with polyp canceration among three age groups was statistically significant(χ2 =5.138,4.107,13.153,P<0.05).The cases of fecal occult blood positive and CEA abnormal increase were gradual-ly increased with age increasing(χ2 =15.544,11.959,P<0.01);with the number of polyps increasing,the cases of fecal occult blood positive showed the increasing trend(χ2 =14.043,P=0.001);the canceration rate in colorectal polyp cases of fecal occult blood positive and CEA abnormal increase was significantly higher than that in the cases of fecal occult blood negative and CEA normal range(χ2 =40.165,43.249,all of P< 0.001).Conclusion The fecal occult blood test and CEA detection results have a certain significance to the follow up for preventing colorectal polyps canceration.

OBJECTIVE:To investigate the characteristics and rules of new and severe ADR induced by TCM for removing blood stasis and clearing heat in our hospital,and to provide reference for safe drug use in clinic. METHODS:New and severe ADR induced by TCM for removing blood stasis and clearing heat reported to national ADR monitoring center were collected from our hospital during Jan. 2006-Dec. 2016. Those ADR cases were analyzed retrospectively in respects of gender,age,allergic history,route of administration,drug type and dosage form,occurrence time,organs/systems involved and clinical manifestations, outcome. RESULTS:Among 298 reports,the incidence of ADR in female(70.13%)was higher male(29.87%),especially in patients aged 50-59(21.48%);there were 77 allergic cases(25.84%). Route of administration was mainly oral administration (57.37%),and dosage form was mainly injection(25.50%). Main ADR-inducing drug was Chinese patent medicine(53.53%). ADR mostly occurred over 1 d after medication(48.32%). Systems/organs involved in ADR were mainly lesion of skin and its appendants,systemic damage and gastrointestinal damage. Main clinical manifestations were rash,contact dermatitis,pruritus, infusion reaction,chills,fever,nausea,vomiting,diarrhea,etc.After drug withdrawal or symptomatic treatment,97.99% patients were revered and cured. There was no death case. CONCLUSIONS:TCM for removing blood stasis and clearing heat causes most new and severe ADR.Clinical drug use should be monitored closely to reduce the occurrence of ADR.