Objective To investigate the alleviation of Nippostrongylus brasiliensis infection on dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice, and to explore the underlying mechanism. Methods Thirty male C57BL/6J mice of the SPF grade, each weighing approximately 25 g, were randomly divided into three groups, including the blank control group (NC group), DSS modeling group (DSS group), and N. brasiliensis treatment group (Nb + DSS group), of 10 mice in each group. Mice in the DSS group were orally administered with 3.5% DSS daily since day 1 (D0) for 6 successive days, and given normal drinking water since D6, and animals in the Nb + DSS group were subcutaneously injected with the third-stage larvae of N. brasiliensis at a dose of 500 larvae per mice 5 days prior to D0, followed by oral administration with 3.5% DSS daily since D0 for 6 successive days and normal drinking water since D6, while mice in the NC group were given normal drinking water. Mouse body weight and stool were observed and the disease activity index (DAI) was scored in each group during the study period. All mice were sacrificed on D9. The mouse colon length was measured, and mouse colon specimens were subjected to hematoxylin-eosin (HE) staining and histopathological scoring. In addition, the mRNA and protein expression of interleukin (IL)-1β and IL-10 was quantified in mouse colon specimens using quantitative fluorescent real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expression of mucosal repair-associated molecules zonula occludens-1 (ZO-1), mucin 2 (MUC2) and claudin-1 was detected in mouse colon specimens using qPCR assay and immunofluorescence assay. Results The mice body weights, DAI scores and colon lengths were (26.26 ± 1.93), (22.39 ± 1.65), (25.00 ± 1.58) g (F = 8.06, P < 0.01); (1.89 ± 0.34), (0.47 ± 0.39), 0 points (F = 57.61, P < 0.000 1); and (42.50 ± 5.75), (56.20 ± 5.96) mm and (61.17 ± 7.88) mm (F = 13.72, P < 0.001) in the NC, DSS and Nb + DSS groups on D9, respectively, and elevated mouse body weight (P < 0.05), reduced DAI score (P < 0.000 1) and increased colon length (P < 0.01) were observed in the Nb + DSS group relative to the DSS group on D9. Pathological examinations showed that the colonic crypts were relatively intact and the inflammatory cell infiltration was lower in the mouse colon specimens in the Nb + DSS group than in DSS the group. There was a significant difference in the histopathological scores of mouse colon specimens among the NC group (0 point), the DSS group [(2.00 ± 1.22) points] and the Nb + DSS group [(0.20 ± 0.45) points] (F = 10.71, P < 0.01), respectively, and the histopathological score of mouse colon specimens was significantly higher in the DSS group than in the NC and Nb + DSS groups (both P values < 0.01). qPCR assay quantified that the relative IL-10 and IL-1β mRNA expression was 1.25 ± 0.08, 0.44 ± 0.14 and 1.30 ± 0.45 (F = 10.66, P < 0.01), and 0.22 ± 0.13, 1.14 ± 0.31 and 0.41 ± 0.19 (F = 16.89, P < 0.001) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and higher IL-10 mRNA expression and lower IL-1β mRNA expression were found in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.01). The relative MUC2, claudin-1 and ZO-1 mRNA expression was 0.87 ± 0.25, 0.34 ± 0.26 and 4.21 ± 0.55 (F = 121.60, P < 0.000 1), 1.05 ± 0.41, 0.16 ± 0.09 and 0.22 ± 0.11 (F = 14.00, P < 0.01), and 1.03 ± 0.10, 0.60 ± 0.11 and 1.64 ± 0.28 (F = 32.16, P < 0.000 1) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and significantly higher MUC2 and ZO-1 mRNA expression was quantified in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). The mean fluorescence intensities of ZO-1 and claudin-1 were 17.18 ± 2.08, 12.38 ± 1.21 and 18.06 ± 2.59 (F = 8.95, P < 0.01) and 13.50 ± 1.63, 9.66 ± 2.03 and 13.61 ± 0.97 (F = 6.96, P < 0.05) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and the mean fluorescence intensities of ZO-1 and claudin-1 were significantly greater in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). Conclusion N. brasiliensis infection may remarkably alleviate DSS-induced ulcerative colitis in mice through promoting expression of anti-inflammatory cytokines, inhibiting expression of pro-inflammatory cytokines and facilitating mucosal repair in colon tissues.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

With the development of information technology and the increasing demand for vaccination services among the people, it is a definite trend to enhance the quality of vaccination services through digitization. This article starts with a clear concept of digital services for vaccination, introduces the current development status in China and abroad, analyzes the advantages and disadvantages of existing models in leading regions, takes a glean from the summation, and proposes targeted solutions. This study suggests establishing a departmental coordination mechanism for data interconnection and sharing, formulating data standards and functional specifications, enhancing the functionalities of the immunization planning information system, strengthening data collection and analytical usage, and intensifying appointment management and science and health education to provide expert guidance for the construction of digital vaccination services across the country in the future.

【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.

Objective:To summarize the strategies and effects of portal vein reconstruction after liver transplantation in recipients with diffuse portal vein thrombosis(PVT).Methods:Clinical data were retrospectively reviewed for 10 PVT patients undergoing liver transplantation(LT)from January 2014 to June 2019. There were 8 males and 2 females with a age of (50.7±10.1)years. The follow-up period was (66.3±25.8)months. Diameter of portal vein anastomosis, diameter and flow velocity of portal vein and presence of ascites were evaluated by color Doppler ultrasound. And computed tomography(CT)was employed for assessing the presence of esophagogastric varices. And patency of portal vein blood flow, therapeutic outcomes of portal hypertension and survival status of recipients were evaluated.Results:Among 7 patients with diffuse PVT without enlarged collaterals, cavoportal hemitransposition( n=6) and renoportal anastomosis( n=1) were performed.Ascites subsided gradually and minimal ascites( n=4) perdisted.Variceal bleeding did not recur within 6 months.As of December 2021, portal vein blood flow remained unobstructed in 4 recipients and 3 patients died.One case of inferior vena cava thrombosis and renal injury at 3 months post operation died of multiple organ failuer at 8 months post-operation.Another patient died of recurrent hepatocarcinoma at 11 months post-operation.Another case died of stroke at 44 months post-operation.Among 3 patients with diffuse PVT complicated with enlarged collaterals, there were right gastric vein to portal vein anastomosis( n=1), gastric coronary vein to portal vein anastomosis( n=1) and pericholedochalvarix to portal anastomosis( n=1). Ascites gradually subsided within 2 months post-operation.Portal vein anastomosis thrombosis was formed 1 month after operation and racanalizated after anticogulation and thrombosis therapies in patient with gastric coronary vein to portal vein anastomosis.Upper gastroinstestinal hemorrhage occurred 36 months after operation and was relieved by endoscopic ligation and sclerotherapy.Blood flow of portal vein was unobstructed in patients with right gastric vein and pericholedochalvarix to portal vein anastomosis.During the last follow-up, velocity of portal vein surpassed 20 cm/s and liver function remained normal in 7 survivors. Conclusions:For patients with complex PVT, portal vein reconstruction may ensure sufficient portal vein blood flow of graft. After operation, portal hypertension disappears and liver function normalizes.

Objective:To evaluate the functional and anatomical outcomes of autologous single retinal pigment epithelium (RPE) transplantation for severe obsolete submacular hemorrhage (SMH) in late age-related macular degeneration (AMD).Methods:A retrospective clinical study. From January 2012 to December 2015, 11 patients with AMD (11 eyes) with obsolete SMH who were diagnosed and treated by pars plana vitrectomy (PPV) combined with autologous RPE transplantation at the Department of Ophthalmology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were included. Among them, there were 9 eyes in 9 males and 2 eyes in 2 females. All the eyes underwent the examinations of best corrected visual acuity (BCVA) and optical coherence tomography; 4 eyes underwent macular fixation function (MAIA) at the same time. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. All eyes were treated with PPV combined with autologous single-layer RPE transplantation or autologous RPE-choroidal full-thickness transplantation, and were divided into S group and C group, with 5 and 6 eyes respectively. The differences of age ( t=-0.363), gender composition ratio ( χ2=0.549), course and thickness of SMH ( t=0.118, 0.231), average times of anti-vascular endothelial growth factor drug treatments ( t=0.129), times of PPV ( t=-0.452) between the two groups were not statistically significant ( P>0.05). The follow-up period was 6-40 months after the operation, and the BCVA, MAIA, graft status and complications of the eyes after the operation were observed. The comparison of continuous variables between groups was performed by independent-sample t test; the comparison of categorical variables was performed by χ2 test. Results:At the last follow-up, the average logMAR BCVA of the eyes in group S and C were 1.62±0.34 and 1.03±0.20, respectively; group C was better than group S, however, the difference was not statistically significant ( t=1.532, P=0.160). There were 4 eyes (80%, 4/5) and 6 eyes (100%, 6/6) in S group and C group with BCVA better than preoperative, the difference was no statistical significance ( χ2=0.677, P=0.895). There were 2 (40%, 2/5) and 3 (50%, 3/6) eyes with logMAR BCVA better than 1.0 in S group and C group, and the difference was not statistically significant ( χ2=0.572, P=0.423). After the operation, 6 eyes of grafts were in good condition and 5 eyes were in poor condition; the BCVA of grafts in good condition was significantly higher than that of poor condition, the difference was statistically significant ( t=4.894, P=0.001). Among the 4 eyes that underwent MAIA examination, 2 eyes were unstable and diffusely fixed on the graft; the fixation point was located at the normal retina adjacent to the graft area in 2 eyes. Secondary subretinal hemorrhage occurred in 3 eyes after the operation; the intraocular pressure was high in 1 eye after the operation. During the follow-up period, no intraocular infection, secondary retinal detachment, recurrent choroidal neovascularization or low intraocular pressure occurred in all eyes. Conclusions:Both autologous single-layer RPE transplantation and autologous RPE-choroidal full-thickness transplantation can help stabilize or even improve the visual function of eyes with severe SMH secondary to advanced AMD. The visual acuity after surgery is closely related to the state of the graft.

Objective:To study the risk factors for acute kidney injury (AKI) after adult orthotopic liver transplantation.Methods:The clinical data of 232 recipients who underwent orthotopic liver transplantation at the First Affiliated Hospital of Zhengzhou University from January 2019 to April 2021 were retrospectively analyzed. There were 195 males and 37 females, aged (49.1±9.4) years old. The patients were divided into two groups according to whether AKI had occurred within 7 days of surgery into the AKI group ( n=112) and the non-AKI group ( n=120). Clinical data including basic information, preoperative hematological indexes, operation time and postoperative hospital stay were compared between the two groups. Factors associated with AKI after orthotopic liver transplantation were studied using univariate analysis and those factors with significant differences were included in multifactorial logistic regression analysis. Results:Among 232 patients who underwent orthotopic liver transplantation, 112 patients developed AKI after surgery, with an incidence of 48.3% (112/232). There were 64 patients with AKI stage 1 (57.1%, 64/112), 30 patients with AKI stage 2 (26.8%, 30/112), and 18 patients with AKI stage 3 (16.1%, 18/112). Logistic regression analysis showed that hypertension ( OR=5.874, 95% CI: 1.931-17.863, P=0.002) and high scores on the model for end-stage liver disease (MELD) ( OR=1.041, 95% CI: 1.010-1.074, P=0.010) were independent risk factors for AKI after orthotopic liver transplantation. Conclusion:Hypertension and MELD score were independent risk factors for postoperative AKI in orthotopic liver transplant recipients.

Objective: Dendrobium polysaccharide(DOP-1-1) was prepared and its effects on the proliferation, differentiation and mineralization of pre-osteoblast MC3 T3-E1 cells were investigated. Methods : A homogeneous polysaccharide(DOP-1-1) was obtained from Dendrobium officinale polysaccharide(DOP) through systematic separation and purification, and the structure of DOP-1-1 was studied by high-performance gel permeation chromatography, monosaccharide analysis, infrared spectroscopy, methylation analysis, GC-MS and NMR spectroscopy.In vitroexperiments were performed to detect the effects of DOP-1-1 on the proliferation, differentiation and mineralization of MC3 T3-E1 cells by MTT method, ALP activity determination and Alizarin Red S staining. At the same time, Western blot was used to determine the effect of DOP-1-1 on the expression of bone-related proteins(Pin1, BMP2, RUNX2) in MC3 T3-E1 cells. Results : DOP-1-1 was a homogeneous polysaccharide with relative molecular weights of 3 611, which was composed of mannose, glucose and galactose. DOP-1-1 had excellent activity of promoting osteoblast proliferation in a low concentration, and the effects of 2.0 and 4.0 μmol/L of DOP-1-1 were equivalent to Positive Control 17β-estradiol(E2). Compared with the control group, E2 and DOP-1-1(4.0, 8.0 μmol/L) increased the ALP activity and mineralization rate in MC3 T3-E1 cells(P<0.01). In particular, the ALP activity and mineralization rate of DOP-1-1(8.0 μmol/L) were higher than those of the positive control E2(P<0.001). In addition, the expression of Pin1, BMP2, and RUNX2 protein in MC3 T3-E1 cells in the DOP-1-1 group was higher than that in the control group(P<0.05). Conclusion DOP-1-1 can promote the proliferation, differentiation and mineralization of MC3 T3-E1 cells in vitro, and its mechanism is related to the activation of Pin1/BMP2 signaling pathway.

Objective:To investigate the clinical significance of changes of serum Clara cell secretory protein(CC16) and pulmonary surfactant protein A(SP-A) in neonates with acute respiratory distress syndrome(ARDS).Methods:The data of 30 neonates with ARDS who needed mechanical ventilation in neonatal intensive care unit of Xi′an Children′s Hospital from January 2016 to November 2018 were collected as observation group, including 12 cases in mild group, 10 cases in moderate group and 8 cases in severe group.The data of healthy newborns during the same period were taken as control group.The serum levels of CC16 and SP-A were detected by ELISA.The serum levels of CC16 and SP-A among different groups were compared.Results:The levels of serum CC16 and SP-A in ARDS group were (59.35±3.67)mg/L and(75.38±6.27)mg/L respectively, (11.26±1.32)mg/L and(18.15±2.69)mg/L in healthy group.The difference was significant( P<0.05). And the differences of serum CC16 and SP-A levels among different degree ARDS groups were significant( P<0.05). The levels of serum CC16 in mild, moderate and severe subgroup were(38.27±16.01)mg/L, (51.25±15.63)mg/L, (84.76±13.12)mg/L and SP-A were(47.02±7.18)mg/L, (73.12±7.98)mg/L, (96.45±12.50)mg/L, which increased with disease severity. Conclusion:Serum CC16 and SP-A are increased and correlated with the severity of neonatal ARDS, which may be used as the index for evaluating the severity of neonatal ARDS in the future.

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 μmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Female ; Heterozygote ; Humans ; Isovaleryl-CoA Dehydrogenase/genetics* ; Male ; Mutation