OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Due to the virtues of no stutter peaks, low rates of mutation, and short amplicon sizes, insertion/deletion (InDel) polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications (Wang et al., 2021). Herein, a self-developed panel of 43 InDel loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing (HCB) including 301 random healthy individuals. The lengths of amplicons at 43 InDel loci in this panel ranged from 87 to 199 bp, which indicated that the panel could be used as an effective tool to utilize highly degraded DNA samples for human identity testing. The loci in this panel were validated and performed well for forensic degraded DNA samples (Jin et al., 2021). The combined discrimination power (PD) and combined probability of exclusion (PE) values in this panel indicated that the 43 InDel loci could be used as the candidate markers in personal identification and parentage testing of HCB. In addition, population genetic relationships between the HCB and 26 reference populations from five continents based on 19 overlapped InDel loci were displayed by constructing a phylogenetic tree, principal component analysis (PCA), and population genetic structure analysis. The results illustrated that the HCB had closer genetic relationships with the Han populations from Chinese different regions.
Beijing ; China ; Forensic Genetics/methods* ; Gene Frequency ; Genetics, Population ; Humans ; INDEL Mutation ; Phylogeny

ObjectiveTo investigate the morphological characteristics of mitral valve annulus in patients with degenerative mitral valve prolapse with severe regurgitation. MethodsA total of 18 patients with mitral valve prolapse complicated with severe regurgitation and 36 patients with normal mitral valve were selected and analyzed using Philips Epic7C echocardiography equipped with transesophageal 3D probe X7-2T and QLAB MVN software. ResultsThe anterolateral and posterio-medium diameter， anterior-posterior diameter， circumference and area of mitral annulus in patients with mitral prolapse complicated with severe regurgitation were larger than those in the control group （P<0.05）. In addition， the annulus parameters in the middle and late systole were higher than those in the early systole （P<0.05）， while the height of the mitral annulus and the non-planar angle showed no difference between the two groups or among different cardiac cycles （P>0.05）. ConclusionsThe three-dimensional morphology and functional of mitral valve annulus changed dynamically with different phases of cardiac cycle. Three-dimensional esophageal echocardiography could provide accurate and detailed information for degenerative mitral valve prolapse with regurgitation.

ObjectiveIn the past， many studies have reported the mode of colorectal cancer（CRC） metastasis， but there is still a lack of research based on long-term follow-up and death as the end point to summarize the location， mode and related survival data of CRC metastasis. MethodsThe data of 373 dead patients with colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University were reviewed， and the location， mode， incidence and survival data of tumor metastasis were statistically analyzed. Results334 patients （89.5%） died of tumor related death. The liver metastasis rate was 51.5%， the lung metastasis rate was 40.4%， and the peritoneal metastasis rate was 55.7%. The number of patients with liver， lung or peritoneal metastasis only was 27 （8%）， 21 （6.3%） and 63 （18.9%） respectively. The prognosis of patients with simple lung metastasis was better （P<0.01）. There were 66 patients （19.7%） with simultaneous metastasis of liver， lung and peritoneum， and the prognosis was the worst （P<0.01）. ConclusionNot all dead colorectal cancer patients have simultaneous metastasis of liver， lung and peritoneum. There are differences in the location and mode of metastasis in different patients， which is related to survival.

ObjectiveA good invasion ability of extravilloustrophoblas (EVTs) is the prerequisite for successful placental colonization and effective remodeling of the uterine spiral artery. This article aims to simulate the pathophysiological process of oxidative stress inducing trophoblasts to pyroptosis in vitro, exploring the correlation between trophoblasts pyroptosis and the pathogenesis of preeclampsia.MethodsTwenty-five patients with preeclampsia were selected from the Department of Obstetrics and Gynecology, Zhongda Hospital affiliated to Southeast University from September 2017 to January 2019. Among them, early-onset preeclampsia (gestational weeks<34) was early-onset group (n=17), late-onset preeclampsia (gestational weeks≥34) was late-onset group (n=8), and full-term pregnant women with normal blood pressure (39＜gestational weeks＞42) were selected as normal group (n=10). Human trophoblasts were cultured with HTR-8/SVneo for 12 hours, and then treated with H2O2 (100, 150, 200, 250μmol/L) (2, 4, 6, 12 h), to induce human trophoblast HTR-8/SVneo pyrolysis model; the control group was normal cultured cells of 1640+10% fetal bovine serum + 1% antibiotics. Placental specimens from 7 patients with preeclampsia were randomly selected, including 3 cases in early onset group, 4 cases in late onset group and 1 case in normal group. The total proteins of cells and placenta were extracted respectively, and the expression of scorch death-related molecular proteins was detected. The mRNA levels of pyroptosis related molecules in cells was detected by RT-qPCR, and the morphological changes of cells were observed by inverted phase contrast microscope.ResultsThe Western blot results showed that the activation of the key molecular activation form of the cell pyrogenesis pathway, Cleaved caspase1, could be detected in the placenta. When H2O2 was 150 mol/L for 2h, the mRNA levels of NLRP3 and IL-1, the key molecules of the upstream activation signal, were significantly up-regulated (8.680±0.481, 14.136±0.244) compared with the control group (1.00±0.00) (P<0.000). At 4h, mRNA levels of key molecule GSDMD and downstream inflammatory factor IL-18 (1.639±0.354 and 1.794±0.043) in the pyrogenesis pathway were significantly higher than those in the control group (1.00±0.00), with statistically significant differences (P<0.05). By reverse validation of the mRNA levels of the molecules associated with pyroptosis, the optimal conditions of the model induced by H2O2 were 150 mol/L and 4h, and the typical changes, such as cell swelling, fragmentation and plasma membrane bubble formation, could be seen under the light microscope.ConclusionThe pyroptosis model of trophoblast cells was successfully established, and the physiological process of oxidative stress inducing trophoblasts to pyroptosis in vitro was successfully simulated, providing new ideas and directions for the diagnosis and treatment of preeclampsia and the development of new drugs.

OBJECTIVE: To investigate the effects of human amniotic mesenchymal stem cell（AMSC） on acute graft-versus-host disease (aGVHD) in xenotransplatation. METHODS: NPG mice were injected with human PBMNC via tail vein to establish a xenografted aGVHD model. The mice in the experimental group were divided into PBMNC infusion group and PBMNC+AMSC co-infusion group, the general condition, survival time and manifestations of aGVHD were observed, the body weight and blood routine indicators were detected, the pathological changes of aGVHD target organs (lung, liver, spleen, small intestine) were observed by HE staining, and the levels of human T cells in peripheral blood, tissues and organs of mice was detected by flow cytometry. RESULTS: The manifestations of aGVHD (lassitude hunchback, shrub, weight reduction, etc.) and the pathological damage of the target organs (lung, liver, spleen, intestine) in PBMNC+AMSC co-infusion group were lighter than those in PBMNC infusion group. Moreover, the PBMNC and AMSC co-infusion significantly reduced the implantion proportion of human T lymphocytes (CD3, CD45) in mice and increased the ratio of CD4/CD8. CONCLUSION Infusion of human-derived AMSC can attenuate the manifestations of aGVHD in mouse xenografts to a certain level, and improve the pathological damage of receptor target organs.