Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD).@*METHODS@#Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins.@*RESULTS@#In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa.@*CONCLUSION@#Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.

A new form of familial platelet disorder caused by germline mutations in RUNX1 in a pedigree / 中华内科杂志

Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.

Efficacy and safety of endoscopic diaphragm incision in children with congenital duodenal diaphragm / 中华儿科杂志

Objective: To explore the efficacy and safety of endoscopic diaphragm incision in pediatric congenital duodenal diaphragm. Methods: Eight children with duodenal diaphragm treated by endoscopic diaphragm incision in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from October 2019 to May 2022 were enrolled in this study. Their clinical data including general conditions, clinical manifestations, laboratory and imaging examinations, endoscopic procedures and outcomes were retrospectively analyzed. Results: Among the 8 children, 4 were males and 4 females. The diagnosis was confirmed at the age of 6-20 months; the age of onset was 0-12 months and the course of disease was 6-18 months. The main clinical manifestations were recurrent non-biliary vomiting, abdominal distension and malnutrition. One case complicated with refractory hyponatremia was first diagnosed with atypical congenital adrenal hyperplasia in the endocrinology department. After treatment with hydrocortisone, the blood sodium returned to normal, but vomiting was recurrent. One patient underwent laparoscopic rhomboid duodenal anastomosis in another hospital but had recurred vomiting after the operation, who was diagnosed with double duodenal diaphragm under endoscope. No other malformations were found in all the 8 cases. The duodenal diaphragm was located in the descending part of the duodenum, and the duodenal papilla was located below the diaphragm in all the 8 cases. Three cases had the diaphragm dilated by balloon to explore the diaphragm opening range before diaphragm incision; the other 5 had diaphragm incision performed after probing the diaphragm opening with guide wire. All the 8 cases were successfully treated by endoscopic incision of duodenal diaphragm, with the operation time of 12-30 minutes. There were no complications such as intestinal perforation, active bleeding or duodenal papilla injury. At one month of follow-up, their weight increased by 0.4-1.5 kg, with an increase of 5%-20%. Within the postoperative follow-up period of 2-20 months, all the 8 children had duodenal obstruction relieved, without vomiting or abdominal distension, and all resumed normal feeding. Gastroscopy reviewed at 2-3 months after the operation in 3 cases found no deformation of the duodenal bulbar cavity, and the mucosa of the incision was smooth, with a duodenal diameter of 6-7 mm. Conclusion: Endoscopic diaphragm incision is safe, effective and less invasive in pediatric congenital duodenal diaphragm, with favorable clinical applicability.

Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease / 中华儿科杂志

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3β phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.

Effect of Erxian Decoction-containing serum on H_2O_2-induced proliferation and osteogenic differentiation of MC3T3-E1 cells via BK channels / 中国中药杂志

This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.

Research progress on moderate and deep sedation during wound dressing change in pediatric burn patients / 中华烧伤杂志

Moderate and deep sedation can effectively relieve or eliminate the pain and body discomfort during wound dressing change in pediatric burn patients, relieve anxiety, agitation, and even delirium of the children, reduce the metabolic rate of the children, make them in a quiet, comfortable, and cooperative state, which is conducive to the smooth completion of dressing change. This paper summarized the three aspects of moderate and deep sedation in pediatric burn patients, including the overview, main points of implementation, and effects, and further introduced the moderate and deep sedation medication regimens for different routes of administration, as well as the content of evaluation and monitoring. Suggestions on the prevention and management of related complications and the management of moderate and deep sedation implementation procedures were put forward, in order to provide references for the development of moderate and deep sedation for wound dressing change in pediatric burn patients in China.

Efficacy and safety of hydroxychloroquine in the treatment of IgA nephropathy: a single-center retrospective analysis / 中华肾脏病杂志

Objective:To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN).Methods:The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi).Results:A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min -1·(1.73 m 2) -1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% ( n=76) and 48.48% ( n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% ( n=85) and 52.78% ( n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% ( n=30) and 53.16% ( n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% ( n=31) and 54.44% ( n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions:HCQ is safe and effective for the treatment of IgAN.

Expression of miR-106b-5p in children with primary immune thrombocytopenia and its correlation with T cells / 中国当代儿科杂志

OBJECTIVES@#To study the expression level of plasma miR-106b-5p in primary immune thrombocytopenia (ITP) and its correlation with the levels of T helper 17 cell (Th17) and regulatory T cell (Treg) and the Th17/Treg ratio.@*METHODS@#A total of 79 children with ITP (ITP group) and 40 healthy children (control group) were selected as subjects. According to the treatment response, the 79 children with ITP were divided into three groups: complete response (n=40), partial response (n=18), and non-response (n=21). Quantitative real-time PCR was used to measure the expression level of miR-106b-5p. Flow cytometry was used to measure the frequencies of Th17 and Treg, and the Th17/Treg ratio was calculated. The correlation of the expression level of plasma miR-106b-5p with the frequencies of Th17 and Treg and the Th17/Treg ratio was analyzed.@*RESULTS@#Compared with the control group, the ITP group had significantly higher levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly lower level of Treg (P<0.05). After treatment, the ITP group had significant reductions in the levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significant increase in the level of Treg (P<0.05). Compared with the partial response and non-response groups, the complete response group had significantly lower levels of miR-106b-5p, Th17, and Th17/Treg ratio (P<0.05) and a significantly higher level of Treg (P<0.05). The correlation analysis showed that in the children with ITP, the expression level of plasma miR-106b-5p was positively correlated with the Th17 level and the Th17/Treg ratio (r=0.730 and 0.816 respectively; P<0.001) and was negatively correlated with the Treg level (r=-0.774, P<0.001).@*CONCLUSIONS@#A higher expression level of miR-106b-5p and Th17/Treg imbalance may be observed in children with ITP. The measurement of miR-106b-5p, Th17, Treg, and Th17/Treg ratio during treatment may be useful to the evaluation of treatment outcome in children with ITP.

Ixazomib-Based Regimen Followed by Autologous Hematopoietic Stem Cell Transplantation in the Treatment of POEMS Syndrome / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of a new proteasome inhibitor Ixazomib followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of POEMS syndrome.@*METHODS@#The clinical manifestations, diagnosis and treatment process and follow-up results of 4 patients with POEMS syndrome who were treated with Ixazomib-based regimen combined with AHSCT in Wuhan No.1 Hospital from February 2018 to July 2020 were analyzed retrospectively. All patients were male, aged from 37-54 years old, with varying degrees of peripheral neuropathy, organ enlargement (liver, spleen or lymph nodes), circulatory overload (peripheral edema and/or pleural effusion), osteosclerosis, endocrine diseases (thyroid, gonads, etc.), skin changes (pigmentation, hemangioma, white nails, etc.), M protein, papilledema and other clinical manifestations and characteristics at the time of initial treatment. Two patients were pathologically diagnosed as hyaline vascular Castleman disease by lymph node biopsy. Three patients underwent lumbar puncture examinations and all showed elevated cerebrospinal fluid protein. All patients received at least 2 cycles of sequential AHSCT after induction chemotherapy based on ixazomib. The follow-up time was 10-28 months, and the median follow-up time was 16 months.@*RESULTS@#All cases survived. The complications were controllable during the treatment. Moreover, the clinical symptoms related to the disease were improved to a certain extent after the treatment. The levels of vascular endothelial growth factor (VEGF) showed a gradual decline.@*CONCLUSION@#Ixazomib combined with AHSCT is safe and effective in the treatment of POEMS syndrome.

Value of autotaxin in predicting refractory Mycoplasma pneumoniae pneumonia in children and its correlation with inflammatory cytokines / 中国当代儿科杂志

OBJECTIVES@#To study the value of autotaxin (an autocrine motility factor) level in serum and bronchoalveolar lavage fluid (BALF) in predicting refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and its correlation with interleukin-6 (IL-6), interleukin-8 (IL-8), and C-reactive protein (CRP).@*METHODS@#A retrospective analysis was performed on 238 children with Mycoplasma pneumoniae pneumonia who were admitted from January 2019 to December 2021. According to disease severity, they were divided into two groups: RMPP (n=82) and general Mycoplasma pneumoniae pneumonia (GMPP; n=156). The two groups were compared in terms of the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF to study the value of autotaxin level in serum and BALF in predicting RMPP in children, as well as the correlation of autotaxin level with IL-6, IL-8, and CRP in children with RMPP.@*RESULTS@#Compared with the GMPP group, the RMPP group had significantly higher levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF (P<0.05). For the children with RMPP, the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF in the acute stage were significantly higher than those in the convalescent stage (P<0.05). The receiver operating characteristic (ROC) curve showed that the level of autotaxin in serum and BALF had a good value in predicting RMPP in children, with an area under the curve of 0.874 (95%CI: 0.816-0.935) and 0.862 (95%CI: 0.802-0.924), respectively. The correlation analysis showed that the level of autotaxin in serum and BALF was positively correlated with IL-6, IL-8, and CRP levels (P<0.001).@*CONCLUSIONS@#The level of autotaxin in serum and BALF increases and is correlated with the degree of disease recovery and inflammatory cytokines in children with RMPP. Autotaxin can be used as a predictive indicator for RMPP in children.

Perifosine inhibits biofilm formation of Pseudomonas aeruginosa by interacting with PqsE protein / 中华预防医学杂志

To explore the biofilm inhibitory efficacy of perifosine against Pseudomonas aeruginosa (P. aeruginos) and its mechanisms. Twenty-fourwell plate was used to form biofilms at the bottom and crystal violet staining was used to determine the biofilm inhibitory effects of perifosine against P. aeruginosa, the wells without perifosine was set as control group. Glass tubes combined with crystal violet staining was used to detect the gas-liqud interface related bioiflm inhibitory effects of perifosine, the wells without perifosine was set as control group. Time-growth curved was used to detect the effects of perifosine on the bacteial planktonic cells growth of P. aeruginosa, the wells without perifosine was set as control group. The interaction model between perifosine and PqsE was assessed by molecular docking assay. The inhibitory effects of perifosine on the catalytic activity of PqsE was determined by detection the production of thiols, the wells without perifosine was set as control group. Binding affinity between perifosine and PqsE was detected by plasma surface resonance. The biofims at the bottom of the microplates and air-liquid interface were effectively inhibited by perifosine at the concentration of 4-8 μg/ml. There was no influence of perifosine on the cells growth of P. aeruginosa. The resuts of molecular docking assay indicates that perifosine could interacted with PqsE with the docking score of -10.67 kcal/mol. Perifosine could inhibit the catalytic activity of PqsE in a dose-dependent manner. The binding affinity between perifosine and PqsE was comfirmed by plasma surface resonance with KD of 6.65×10-5mol/L. Perifosine could inhibited the biofilm formation of P. aeruginosa by interacting with PqsE.

Minocycline Activates the Nucleus of the Solitary Tract-Associated Network to Alleviate Lipopolysaccharide-Induced Neuroinflammation / 中国医学科学杂志(英文版)

Objective To examine the neuroanatomical substrates underlying the effects of minocycline in alleviating lipopolysaccharide (LPS)-induced neuroinflammation. Methods Forty C57BL/6 male mice were randomly and equally divided into eight groups. Over three conse-cutive days, saline was administered to four groups of mice and minocycline to the other four groups. Immediately after the administration of saline or minocycline on the third day, two groups of mice were additionally injected with saline and the other two groups were injected with LPS. Six or 24 hours after the last injection, mice were sacrificed and the brains were removed. Immunohistochemical staining across the whole brain was performed to detect microglia activation via Iba1 and neuronal activation via c-Fos. Morphology of microglia and the number of c-Fo-positive neurons were analyzed by Image-Pro Premier 3D. One-way ANOVA and Fisher's least-significant differences were employed for statistical analyses. Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by reduced activation of microglia in multiple brain regions, including the shell part of the nucleus accumbens (Acbs), paraventricular nucleus (PVN) of the hypothalamus, central nucleus of the amygdala (CeA), locus coeruleus (LC), and nucleus tractus solitarius (NTS). Minocycline significantly increased the number of c-Fo-positive neurons in NTS and area postrema (AP) after LPS treatment. Furthermore, in NTS-associated brain areas, including LC, lateral parabrachial nucleus (LPB), periaqueductal gray (PAG), dorsal raphe nucleus (DR), amygdala, PVN, and bed nucleus of the stria terminali (BNST), minocycline also significantly increased the number of c-Fo-positive neurons after LPS administration. Conclusion Minocycline alleviates LPS-induced neuroinflammation in multiple brain regions, possibly due to increased activation of neurons in the NTS-associated network.

Efficacy of individualized rituximab as the rescue therapy for active lupus nephritis with acute kidney injury / 中华肾脏病杂志

Objective:To investigate the efficacy and safety of individualized rituximab rescue therapy for active lupus nephritis with acute kidney injury (AKI).Methods:The clinical data of lupus nephritis patients with AKI treated with rituximab at the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University School of Medicine from April 2017 to June 2020 were collected, and the renal remission rate and adverse events after rituximab treatment were analyzed retrospectively. The Kaplan-Meier method was used to calculate the cumulative incidence of patients' remission.Results:There were 13 patients enrolled, including 8 females, and aged (35.23±15.92) years old. The urinary protein/creatinine ratio was (5.22±1.57) g/g before rituximab treatment. Four patients were on dialysis at admission, and 9 patients without dialysis had serum creatinine of (223.22±85.73) μmol/L. Eight patients were confirmed as proliferative lupus nephritis by renal biopsies, including 7 cases with crescent formation and 1 case with thrombotic microangiopathy (TMA), and the other 5 cases without renal biopsies were clinically diagnosed as TMA. The dose of rituximab was (815±516) mg (200-2 100 mg), and all the patients reached the state of peripheral blood B cells clearance (CD19 + B cell count was<5/μl). After the first treatment of rituximab, the median time to B-cell clearance was 21(15, 35) days, and 8 patients reached B-cell depletion (CD19 + B cell count was 0). The remission rate was 12/13 (two cases reached complete remission, and 10 cases reached partial remission). Three cases stopped dialysis, and 1 case (with glomerulosclerosis of 52.94%) entered maintaining dialysis. The relapse times in the maintenance remission period of 7 patients with refractory lupus nephritis declined significantly from (1.57±0.53) times in a median history of 60(20, 109) months to (0.43±0.79) times in a median history of 18(10, 23) months after the use of rituximab ( P=0.015). After using rituximab, the incidence of infection was 7/13. The median time from the use of rituximab to infection was 26(4, 44) days. Pulmonary infection (5/13) was the most common type and all infected patients recovered after anti-infection treatment. Conclusions:Rituximab can be used in the treatment of active lupus nephritis with AKI, especially in patients with crescent formation and TMA, but the infection should be paid close attention to and prevented.

Clinical application of 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus / 中华肾脏病杂志

Objective:To analyze the weight score and clinical application of 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) systemic lupus erythematosus (SLE) classification criteria in lupus nephritis patients.Methods:Lupus nephritis patients with renal biopsy results who were admitted in the First Affiliated Hospital of Zhejiang University College of Medicine between January 2014 and December 2018 were enrolled retrospectively. According to whether these patients were treated with glucocorticoids and/or immunosuppressants at the time of renal biopsy, they were divided into untreated group and post-treatment group. The weight scores were compared between the two groups, and the relationship between each weight score and remission after treatment was analyzed. Taking no remission as the end event, Cox regression analysis was used to analyze the influence of each weighted integral on the end event.Results:A total of 153 patients were enrolled, including 131 (85.6%) females. These were 70 (45.8%) patients in the untreated group and 83 (54.2%) patients in the post-treatment group. The patients in the untreated group had higher scores of fever (>38.3℃), blood system involvement, low complement and positive specific antibodies than those in post-treated group (all P<0.05). In a median follow-up of 34 (6-50) months, 99 patients (64.7%) achieved complete remission, 38 patients (24.8%) achieved partial remission and 16 patients (10.5%) had no remission. With no remission as the endpoint event, univariate Cox regression analysis showed that proliferative lupus nephritis (renal score of 10 points vs 8 points) and neuropsychiatric involvement were the risk factors (both P<0.05), while multivariate Cox regression analysis showed that neuropsychiatric involvement ( HR=4.758, 95% CI 1.324-17.101, P=0.017) was an independent risk factor. Conclusion:The weight scores of 2019 EULAR/ACR SLE classification diagnostic criteria have certain predictive value for remission of patients with lupus nephritis.

Correlation of Chemical Components in Periploca forrestii with Ecological and Soil Factors / 中国实验方剂学杂志

Objective:To study the correlation of eight chemical components in Miao medicine <italic>Periploca forrestii</italic> from different producing areas with the ecological and soil factors. Method:The contents of neochlorogenic acid， chlorogenic acid， cryptochlorogenic acid， isochlorogenic acid B， isochlorogenic acid A， isochlorogenic acid C， procyanidin A₂， and periplocin were simultaneously determined by ultra-performance liquid chromatography （UPLC）. The root soil samples from various producing areas were collected for testing various soil factors， followed by climate data extraction with ArcGIS and topographic data recording using GPS. SPSS 24.0 was employed to conduct the bivariate analysis and stepwise regression analysis of the eight chemical components in <italic>P. forrestii</italic> from different producing areas with the ecological and soil factors. Result:Stepwise regression equations of the content of eight chemical components against ecological and soil factors were established. The findings demonstrated that neochlorogenic acid was negatively correlated with precipitation in the coldest season and chlorogenic acid negatively correlated with precipitation in the driest month. Cryptochlorogenic acid was negatively correlated with precipitation in the coldest season and average temperature in the warmest season， but positively with selenium. Isochlorogenic acid B was mainly affected by soil factors. Specifically， it was positively correlated with available iron and molybdenum but negatively with total phosphorus and available phosphorus. Isochlorogenic acid A was positively correlated with molybdenum but negatively with the coefficient of variation of precipitation. Isochlorogenic acid C showed a positive correlation with exchangeable magnesium. Procyanidin A₂ exhibited a positive correlation with molybdenum and a negative correlation with available potassium. Periplocin was negatively correlated with the coefficient of variation of precipitation. Conclusion:The correlation between the eight chemical components of <italic>P. forrestii</italic> and the ecological and soil factors has been clarified， which will provide reference for the introduction， cultivation， and standardized planting of <italic>P. forrestii </italic>and also a theoretical basis for further research on its ecological and soil factors and quality formation mechanism.

Application effect of magnetic service concept in clinical nursing for patients with acute gastroenteritis / 中国实用护理杂志

Objective:To explore the application effect of magnetic service concept in clinical nursing for patients with acute gastroenteritis.Methods:A total of 101 patients with acute gastroenteritis undergoing magnetic service concept intervention in gastroenterology department of Lishui Central Hospital were selected as study group from January 2019 to January 2020, other 97 patients with acute gastroenteritis undergoing routine nursing intervention were enrolled as control group from January to December 2018. The scores of Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), self-care ability and quality of life before and after intervention were observed and compared between the two groups. The scores of nursing satisfaction were recorded and compared between the two groups.Results:After nursing, HAMA and HAMD scores in study group were (13.39 ± 4.56) and (17.89 ± 6.63) points, which were significantly lower than those in control group (18.60 ± 6.79) and (21.51 ± 6.03) ( t values were 6.36 and 4.11, P<0.05). After nursing, scores of self-concept, self-responsibility, self-care skills and health awareness in study group were (79.12 ± 4.98), (79.85 ± 5.47), (80.22 ± 3.89) and (76.25 ± 5.98) points, which were higher than those in control group (52.08 ± 3.63), (58.88 ± 7.25), (57.65 ± 3.62), (54.12 ± 5.06) points (t values were 23.06-43.41, P<0.05). After nursing, scores of physiology, mentality, emotion and social contact in study group were (69.14 ± 4.21), (82.13 ± 6.12), (71.25 ± 5.28) and (82.95 ± 7.22) points, which were higher than those in control group (60.41 ± 3.26), (69.57 ± 4.26), (57.13 ± 3.21), (68.07 ± 5.14) points (t values were 16.27-33.63, P<0.05). The scores of satisfaction with life care, regular wards inspections, bell calling, service attitudes and health education in study group were (90.40 ± 6.80), (91.38 ± 6.82), (90.22 ± 4.96), (90.88 ± 5.56) and (92.46 ± 6.38) points, which were higher than those in control group (81.22 ± 5.83), (80.44 ± 4.25), (82.12 ± 4.65), (83.24 ± 4.56), (82.06 ± 3.55) points (t values were 10.18-14.09, P<0.05). Conclusions:The magnetic service concept can improve psychological status and quality of life in patients with acute gastroenteritis, enhance self-care ability and nursing satisfaction.

A comparative study on physical fitness of primary and secondary school students in Maonan Ethnic Areas in 2014 and 2019 / 中国学校卫生

Objective@#To provide reference for the overall education of Maonan primary and secondary school students by understanding the physical status.@*Methods@#Physical fitness test were administered in 1 107 boys and 1 236 girls in 2014,as well as 1 130 boys and 1 308 girls in 2019 of Maonan Nationality aged from 7 to 18 years old.@*Results@#Compared with 2014, the height of boys and girls aged 7-18 increased by 1.5 cm and 1.1 cm on average in 2019, and there were differences in boys height among 6 age groups ( P <0.05) and girls height among 5 age groups( P <0.05). The increase of vital capacity was 126 mL, and there were differences in the vital capacity of boys in 10 ages ( P <0.05) and girls in 11 age groups( P <0.05). The results of 50 m running are improved by 0.2 s and 0.4 s on average. There are differences in 7 ages of boys 50 m running results ( P <0.05), and there are differences in 11 age groups of girls 50 m running results( P <0.05). The average 1 000 m score of male students increased by 3.7 s, and there were differences among 4 age groups( P <0.05). The average 800 m score of female students increased by 12.8 s, and there were differences among 4 age groups( P <0.05).@*Conclusion@#Maonan primary and secondary school students body shape, physical function and sports quality are on the rise as a whole, and fluctuate in some age groups.

A novel homozygous frameshift mutation in / 亚洲男科学杂志(英文版)

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

Predictive factors for glucocorticoid therapy in children with eosinophilic gastroenteritis / 中国当代儿科杂志

OBJECTIVES@#To study the predictive factors for glucocorticoid therapy by analyzing the association between the clinical features and treatment regimens in children with eosinophilic gastroenteritis.@*METHODS@#A retrospective analysis was performed on the medical data of 182 children with eosinophilic gastroenteritis who were admitted to Guangzhou Women and Children's Medical Center from January 2012 to December 2020. According to whether glucocorticoids were used, these children were divided into a glucocorticoid treatment group and a control group. The two groups were compared in terms of age, history of allergy, clinical symptoms, laboratory examination results, endoscopic findings, and pathological results of gastrointestinal mucosa. A multivariate logistic regression analysis was performed for the results with statistical significance.@*RESULTS@#Of the 182 children, 36 (19.8%) received glucocorticoid therapy. The rates of hematochezia, anemia, and mucosal ulceration/luminal stenosis under endoscopy and the mucosal eosinophil infiltration count were significantly higher in the glucocorticoid treatment group than those in the control group (@*CONCLUSIONS@#Mucosal ulceration/luminal stenosis under endoscopy or a significant increase in the mucosal eosinophil infiltration count based on pathology suggests that glucocorticoid therapy can be considered in children with eosinophil gastroenteritis.