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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.
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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/metabolismABSTRACT
Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2
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Background Regional differences in economic development, natural environment, health care level, and social structure may lead to differences in the provincial distribution of the health status of the elderly population. Objective To explore the provincial distribution characteristics, regional differences, and influencing factors of the self-assessed health of the elderly population, with the aim of providing a policy basis for improving the health of the elderly population and promoting healthy aging according to local conditions. Methods Using 31 provinces (municipalities and autonomous regions) in China as the basicstudy unit and based on the method of Wagstaff, the self-rated health data of the elderly population (aged 60 years and above) in each province from the 2010 and 2020 national censuses and the 2015 1% National Population Sample Survey were converted into ill-health scores as a measure of self-assessed health, and higher scores represented worse health status perception. Global Moran's I was used to evaluate spatial autocorrelation, range [−1, 1], with a value of 1 as a perfect clustered pattern. Local Moran's I was used to evaluate the tendency of local autocorrelation, and high-high aggregation/low-low aggregation indicated that both target province and its neighboring provinces showed higher/lower ill-health scores. Spatial econometric models were selected by Lagrange multiplier test and Hausman test to explore influencing factors of the self-assessed health of the elderly population. Results In 2010, 2015, and 2020, the national ill-health scores of the elderly population were 1.831, 1.873, and 1.547, respectively, and the corresponding Global Moran's I statistics were 0.347, 0.482, and 0.511, respectively (P<0.01), indicating that the ill-health scores of the elderly population showed a significant spatial positive autocorrelation, and the degree of spatial aggregation was increasing gradually. From 2010 to 2020, the high-high aggregation of ill-health scores among the elderly population was concentrated in the inland northwest, while the low-low aggregation was concentrated in the southeast coast, gradually showing a "southeast-central-northwest" stepped incremental pattern of differentiation. The Lagrange multiplier test and Hausman test suggested that the fixed-effects spatial lagged model was a better choice, and the regression model showed a spatial autocorrelation in the ill-health scores of the elderly population, with an autocorrelation coefficient of 0.3969 (P<0.001); the ill-health scores of the elderly population were negatively correlated with the natural logarithms of gross regional product per capita, and the number of beds in health care facilities per 1000 population, with regression coefficients of −0.8297 and −0.0454 (P<0.05) respectively, and positively correlated with the annual average concentration of PM2.5, illiteracy rate, and the number of health technicians per 1000 population, with regression coefficients of 0.0033, 0.0297, and 0.0765 (P<0.05), respectively. Conclusion From 2010 to 2020, the overall self-assessed health level of China's elderly population showed an upward trend and a spatial positive autocorrelation, with better self-assessed health in the southeast coast and poorer ratings in the northwestern inland. Additionally, there was a gradual decline in self-assessed health of the elderly population from the southeast to the central regions and further to the northwest in terms of spatial distribution. Economic development level, environmental pollution, health resource allocation, and education level are important factors influencing the self-assessed health of the elderly population.
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Photodynamic therapy (PDT) is a new modality for cancer therapy, which has been used in the clinical treatment for various tumors, such as skin cancer, bladder cancer and prostate cancer. Most photosensitizers have the disadvantages of hydrophobic, low bioavailability and the limited tumor targeting ability. The nanoscale delivery systems can improve the solubility of photosensitizers and enhance their accumulation at the tumor sites. The multifunctional nano-delivery systems are prepared in combination with other anti-tumor drugs to enhance the anti-tumor effect. In addition to addressing the issues of poor solubility and the insufficient tumor targeting ability, the nanoscale delivery systems need to improve the pharmacokinetic properties of photosensitizers, facilitating their rapid accumulation at the tumor sites and quick elimination in vivo, and reducing the skin phototoxicity. This review summarizes the recent clinical application of PDT of cancer, the development of photosensitizers, the delivery systems for photosensitizers and the combinatorial application with other therapeutic methods. The goal is to present an understanding of knowledge on the design of new types of photosensitizers and its clinical application in PDT of cancer.
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The Tongmai Yangxin pill (TMYX) has potential clinical effects on no-reflow (NR); however, the effective substances and mechanisms by which this occurs remain unclear. This study evaluates the cardioprotective effects and molecular mechanisms of TMYX against NR. We used a myocardial NR rat model (2 h after myocardial ischemia and 2 h after reperfusion) to confirm the effect and mechanism of action of TMYX in alleviating NR. In vitro studies in isolated coronary microvasculature of NR rats and in silico network pharmacology analyses were performed to reveal the underlying mechanisms of TMYX and determine the main components, targets, and pathways of TMYX, respectively. The experiment was approved by the Ethics Committee of Hunan University of Chinese Medicine (LLBH-202212160001). TMYX showed therapeutic effects on NR by improving cardiac structure and function, reducing NR, ischemic areas, and cardiomyocyte injury, and decreasing the content of cardiac troponin I (cTnI). Moreover, the mechanism of TMYX predicted by network pharmacology is related to the hypoxia inducible factor-1 (HIF-1), nuclear factor kappa-B (NF-κB), and tumor necrosis factor (TNF) signaling pathways. TMYX increased the expression of G protein-coupled estrogen receptor (GPER), phospho-extracellular signal-regulated kinase (p-ERK), and HIF-1α. In vitro, TMYX enhanced the diastolic function of coronary microvascular cells; however, this effect was inhibited by GPER inhibitor (G-15), eNOS inhibitor (L-NAME), and sGC inhibitor (ODQ). This study integrates pharmacology and experimental evaluation to reveal that TMYX activates HIF-1α/eNOS signaling pathway by upregulating GPER to relax coronary microvessels, thereby significantly alleviating NR.
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Xanthine oxidoreductase (XOR), the key enzyme catalyzing purine to produce uric acid, including two subtypes, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), respectively, in vivo. Usually, XDH and XO can transform to each other. In this study, based on the principle that the subtype XO or XDH uses different electron acceptors, the methods for the measuring the activities of bovine milk XOR (pure enzyme) and its subtypes were established. The optimal concentrations of substrate xanthine (50 μmol·L-1) and electron acceptor NAD+ (50 μmol·L-1), pH value (7.80) were investigated. The ranges of the XOR, XO, XDH activity which could be determined were 0.97-17.5 U·L-1, 1-9 U·L-1, and 66-1 191 mU·L-1, respectively. Furthermore, the methods for determining the activities of XOR and its subtypes in mouse liver were established. The preparation of liver samples, the optimal concentrations of xanthine (100 μmol·L-1) and NAD+ (100 μmol·L-1) were researched. And the activity ranges of XOR, XO and XDH in mouse liver which could be determined were 0.67-3.98, 0.19-1.08, and 0.52-3.55 U·gprot-1, respectively. With the methods above, the effects of classic XOR inhibitor allopurinal (Allo) on XOR, XO and XDH from both milk and mouse liver were determined. All animal experiments have been approved by the Animal Experimental Center, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College (00003346). This study established new methods for the determination of XOR and its subtypes activity in pure enzyme system and in mouse liver, respectively, which were accurate and convenient. It laid the experimental foundation for exploring the different pathophysiological effects of XOR in the body and developing new XOR inhibitors.
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Objective: To study the correlation between ceramic and chronic obstructive pulmonary disease (COPD), and explore its related risk factors. Methods: In January 2021, five representative ceramic enterprises were selected from Chancheng District, Nanhai District, Gaoming District and Sanshui District of Foshan City. The ceramic workers who came to Chancheng Hospital of Foshan First People's Hospital for physical examination from January to October 2021 were selected as the research objects, and 525 people were included. Conduct questionnaire survey and pulmonary function test. Logistic regresion was performed to analyze the influencing facters of COPD among ceramic workers. Results: The subjects were (38.51±1.25) years old, 328 males and 197 females, and the detection rate of COPD was 9.52% (50/525). The incidence of respiratory symptoms such as dyspnea, chronic cough, wheezing and chest tightness, the detection rates of abnormal lung age, abnormal lung function and COPD in males were higher than those in females (P<0.05). The logistic regression analysis showed that male, age, working years, smoking status and family history of COPD were the risk factors for COPD among ceramic workers (P<0.05) . Conclusion: The ceramic workers are the high risk population of COPD. We should do a good job in health education, and do a regular physical examination to find the changes of lung function in time, and prevent the occurrence of COPD as soon as possible.
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Female , Humans , Male , Adult , Pulmonary Disease, Chronic Obstructive/epidemiology , Ceramics , Health Education , Hospitals , Physical ExaminationABSTRACT
Objective:To evaluate the role of activation of vesicular glutamate transporter 2 (VGLUT2) neurons in vagal nodose ganglion in dexmedetomidine-caused bradycardia in mice.Methods:Ninety-six SPF healthy male VGLUT2-cre mice, aged 10 weeks, weighing 20-25 g, were divided into 6 groups ( n=16 each) by the random number table method: normal saline control group (NS group), dexmedetomidine group (Dex group), viral control + chemogenetic control + dexmedetomidine group (eGFP-NS+ Dex group), viral transfection + chemogenetic control + dexmedetomidine group (hM4Di-NS+ Dex group), viral control + chemogenetic inhibition + dexmedetomidine group (eGFP-CNO+ Dex group) and viral transfection + chemogenetic inhibition + dexmedetomidine group (hM4Di-CNO+ Dex group). Dexmedetomidine 100 μg/kg was intraperitoneally injected in Dex group. The equal volume of normal saline was intraperitoneally injected in NS group. AAV2/9-hSyn-DIO-hM4Di-eGFP was injected in the right nodose ganglion in hM4Di-NS+ Dex group and hM4Di-CNO+ Dex group, and AAV2/9-hSyn-DIO-eGFP was injected in the right nodose ganglion in eGFP-NS+ Dex group and eGFP-CNO+ Dex group, allowing the virus expression for 21 days. On the 22nd day after virus injection, clozapine-n-oxide (CNO) 5 mg/kg was intraperitoneally injected in hM4Di-CNO+ Dex group and eGFP-CNO+ Dex group, the equal volume of normal saline was intraperitoneally injected in hM4Di-NS+ Dex group and eGFP-NS+ Dex group, 1 h later the efficacy of CNO reached the peak, and then dexmedetomidine 100 μg/kg was intraperitoneally injected. The respiratory rate, heart rate, SpO 2 and discharge frequency of the right vagal nodose ganglion were synchronously measured by multi-channel electrophysiology in vivo. The expression of phosphorylated extracellular signal-regulated kinase (pERK) and VGLUT2 and co-expression of pERK and VGLUT2 in the right vagal nodose ganglion were detected by immunofluorescence assay. Results:Compared with NS group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in the other five groups ( P<0.05). Compared with Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly decreased, and pERK expression was down-regulated in hM4Di-CNO+ Dex group, and no significant change was found in the parameters mentioned above in hM4Di-NS+ Dex group, eGFP-NS+ Dex group and eGFP-CNO+ Dex group ( P>0.05). Compared with hM4Di-CNO+ Dex group, the percentage of heart rate variation and neuron firing frequency after administration were significantly increased, and pERK expression was up-regulated in eGFP-CNO+ Dex group ( P<0.05). There was no significant difference in the percentage of respiratory variation and SpO 2 among the six groups ( P>0.05). The expression of VGLUT2-positive neurons was abundant in nodose ganglia, and the co-expression rate of pERK and VGLUT2 was nearly 90%. The co-expression rate of pERK and VGLUT2 decreased to about 30% after inhibition of VGLUT2 neurons in ganglion. Conclusions:The mechanism by which dexmedetomidine causes bradycardia is associated with activation of VGLUT2 neurons in vagal nodose ganglia in mice.
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Objective:To explore the risk factors of acute kidney injury(stage 3)developed within 48 hours in elderly patients with sepsis, and to use them to develop a risk prediction model and then evaluate and externally validate the model.Methods:Clinical data of all elderly patients(age≥ 60 years)with sepsis in the intensive care medicine information database(MIMIC-Ⅳ v1.0)were extracted.Independent risk factors were determined by multivariate logistic regression analysis.A risk prediction model was constructed, a nomogram was drawn, and the receiver operating characteristic curve(ROC)and the Hosmer-Lemeshow(H-L)test were used to evaluate the model's prediction accuracy and R-squared.Clinical data of elderly patients(age≥ 60 years)with sepsis admitted to the Department of Critical Care Medicine of the Second People's Hospital of Hefei from May 2019 to October 2021 were retrospectively collected and fed into the prediction model to conduct external validation.Results:A total of 1 977 elderly patients with sepsis were screened out from the MIMIC-IV database and included in the training set, of whom, 544 developed AKI-stage 3 within 48 hours.Univariate analysis was performed for factors that might be associated with acute kidney injury in elderly patients with sepsis.Compared with the normal group that did not progress to AKI stage 3, there were statistically significant differences in 28 indicators, such as the duration of ICU stay, intravenous fluid intake in 24 hours, and use of vasoactive drugs[5(3, 9)d vs.7(4, 12)d; 2.05(1.17, 3.27)ml·kg -1·h -1vs.2.37(1.47, 4.10)ml·kg -1·h -1; 761(53.11%) vs.375(68.93%), P<0.001]. Based on the results of multivariate logistic regression analysis, a prediction model was finally constructed with 9 variables: albumin( OR=0.983, 95% CI: 0.966-0.999, P=0.040), aspartate transaminase( OR=1.000, 95% CI: 1.000-1.000, P<0.001), APTT( OR=1.005, 95% CI: 1.001-1.009, P=0.028), total bilirubin( OR=1.003, 95% CI: 1.001-1.004, P=0.001), serum creatinine( OR=1.005, 95% CI: 1.004~1.007, P<0.001), Charlson score( OR=1.117, 95% CI: 1.061-1.177, P<0.001), intravenous fluid intake in 24 hours( OR=1.101, 95% CI: 1.034-1.173, P=0.003), weight( OR=1.023, 95% CI: 1.018-1.029, P<0.001), and mechanical ventilation( OR=2.412, 95% CI: 1.843-3.157, P<0.001). Then a nomogram was generated.The area under the ROC curve(AUC)of the prediction model was 0.755(95% CI: 0.731-0.780), and the H-L test was conducted( χ2=10.89, P=0.208>0.05), indicating a good fit.Data from 102 elderly patients were included in the validation set, with 27 cases that had developed AKI-stage3 within 48 hours, and were fed into the prediction model, with an AUC of 0.778(95% CI: 0.676-0.880)and χ2=3.72 and P=0.882>0.05 from the H-L test, consistent with the results of the training set. Conclusions:The model has some predictive value for acute kidney injury in elderly patients with sepsis.
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Objective:To explore the Epstein-Barr virus (EBV) latent infection membrane protein (LMP) 1 or LMP2 specific T cell immune response and clinical significance in stage III-IVa nasopharyngeal carcinoma (NPC), aiming to provide ideas and evidence for immunotherapy in NPC.Methods:Fifty-nine NPC patients admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from February 2018 to October 2020 for primary treatment were collected. Peripheral blood monocytes (PBMCs) were stimulated by LMP antigen. Intracellular cytokine staining and flow cytometry were applied to study the expression levels of IL-2, IL-13, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) from CD4 + T and CD8 + T cells, and then analyzed in conjunction with clinical factors. Results:The positive rates of total PBMCs to LMP1 and LMP2 in NPC patients were different. The positive rate of LMP1 specific CD4 + T cells was statistically higher in stage T 3-T 4 NPC than that in stage T 1-T 2 (51.0% vs. 10.0%, P=0.042). There were also differences in the expression of cytokines between LMP1 and LMP2, CD4 +T cells and CD8 +T cells. Survival analysis showed the 2-year and 3-year overall survival (OS) rates were 91.5% and 88.2%, and the 2-year and 3-year progression-free survival (PFS) rates were 83.3% and 75.3%. Univariate analysis suggested that smoking history, male and LMP1 stimulated IL-13 positive expression in CD4 + T cells affected the disease progression ( P=0.026, 0.045 and 0.006); multivariate analysis showed LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history were the independent prognostic factors affecting PFS ( P=0.017, 0.019). Conclusions:LMP1 and LMP2 generate specific T-cell immune response in PBMCs of NPC patients, with differential expression in two T-cell subsets. LMP1 and LMP2 specific T cell immune response is associated with primary tumor size and metastatic lymph node volume. LMP1 stimulated IL-13 positive expression in CD4 + T cells and smoking history affects the disease progression.
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Objective:To investigate the relationship between arterial blood partial pressure of carbon dioxide and neurological outcome after cardiopulmonary resuscitation.Methods:The clinical data of 116 patients who underwent cardiopulmonary resuscitation admitted to the Intensive Care Unit and Emergency Department of the Second People's Hospital of Hefei from January 2018 to January 2020 were retrospectively analyzed. According to the average arterial blood partial pressure of carbon dioxide within 24 hours after admission, patients were divided into normal (35 mmHg ≤ PaCO 2 ≤ 55 mmHg, 1 mmHg = 0.133 kPa, n = 44), hypercapnia (PaCO 2 > 55 mmHg, n = 51), and hypocapnia (PaCO 2 < 35 mmHg, n = 21) groups. ICU stay, in-hospital mortality, and neurological outcome at discharge were compared among groups. A logistic regression analysis model was established. The relationship between PaCO 2 and neurological outcome was determined. Results:There were no significant differences in age, sex, cardiac arrest time, acute physiological and chronic health evaluation II score at admission, 1-hour mean arterial pressure, location of cardiac arrest, and initial heart rhythm among the three groups (all P > 0.05). ICU stay in the normal group [(7.23 ± 2.55) days] was significantly higher than that in the hypercapnia [(12.21 ± 4.12) days] and hypocapnia [(11.78 ± 4.72) days] groups ( t = 6.48, 4.59, both P < 0.01). In-hospital mortality in the normal group was 38.6% (17/44), which was significantly lower than 60.8% (31/51) in the hypercapnia group and 66.7% (14/21) in the hypocapnia group ( χ2 = 4.63, 4.47, both P < 0.05). The good neurological outcome rate in the normal group was 55.6% (15/44), which was significantly higher than 25.0% (5/51) in the hypercapnia group and 28.6% (2/21) in the hypocapnia group ( χ2 = 8.38, 5.14, both P < 0.05). Multivariate logistic regression analysis showed that cardiac arrest time, 1-hour mean arterial pressure, acute physiological and chronic health evaluation II score, and PaCO 2 are important factors for neurological outcomes of resuscitated patients at discharge (all P < 0.01). Conclusion:Within 24 hours after cardiopulmonary resuscitation, maintaining a normal PaCO 2 level can help improve the neurological outcome of patients at discharge.
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Objective:To investigate the feasibility and effectiveness of the blended teaching model for diagnostic radiology based on BOPPPS classroom reconstruction, i.e., bridge-in, objective, pre-assessment, participatory-learning, post-assessment, and summary.Methods:The undergraduate students in the classes of 2017 and 2018 in Department of Medical Imaging were selected as research subjects. The students in the class of 2018 were established as observation group and received the innovative blended teaching model based on BOPPPS classroom reconstruction, and those in the class of 2017 were established as control group and received teaching with traditional theoretical lectures. At the end of the course, 80 students were randomly selected from the observation group and the control group for performance analysis and teaching evaluation. SPSS 26.0 was used to perform the t-test. Results:The observation group had a total score of (82.66±6.18), while the control group had a total score of (76.47±5.42), and compared with the control group, the observation group had significantly higher scores of homework score, course discussion, and final examination ( P<0.05). Compared with the control group, the observation group had significantly higher scores of "understanding of the basic knowledge of imaging", "improvement of comprehensive diagnostic thinking ability", "stimulating the interest in learning and expanding horizons", and "cultivating clinical competence" in the self-evaluation survey ( P<0.05). Conclusion:The blended teaching model based on BOPPPS classroom reconstruction is suitable for the teaching of radiology diagnostics. It not only enriches teaching means and methods and enhances classroom participation and interaction, but also expands teaching space and teaching content.
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Objective:To investigate the efficacy and application value of vacuum sealing drainage (VSD) in high-risk incision after bone and soft tissue tumor surgery.Methods:From January 2020 to September 2022, 22 patients with high-risk incisions after bone and soft tissue tumor resection in Shengjing Hospital, China Medical University were treated with VSD. The postoperative negative pressure was set at 0.025 MPa (188 mmHg, 1 mmHg = 0.133 kPa), and the VSD device was removed on the 7th day after operation. After removal, the wound healing and the incidence of related complications were observed.Results:After removing the VSD, 20 patients with high-risk incisions reached the standard of grade A healing, the rate of grade A healing was 90.91%, and 2 patients had incision wound necrosis, and the incision healed were improved after dressing change. The patients were followed up for 6 - 12 months, with an average time of 10 months. The wound healing of all patients reached the standard of grade A healing, and no long-term complications occurred.Conclusions:VSD technique has good clinical effect and can be applied to various high-risk incisions after bone and soft tissue tumor surgery, which can effectively prevent the occurrence of incision complications.
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Objective:To analyze the disease spectrum of lysosomal storage disorders(LSDs) and explore the prevalent distributions of different LSD types in one center in Shanghai.Methods:A retrospective analysis was made.A total of 5 476 suspected LSD patients, including 3 415 males and 2 061 females, with a median age of 4 years(1 day to 72 years), were collected from Xinhua Hospital, Shanghai Jiaotong University School of Medicine from August 2008 to May 2022.The activity of different lysosomal enzymes was detected by fluorescent and biochemical methods.Results:A total of 1 520 patients were diagnosed with LSDs, including 972 males and 548 females, with a median age of 4 years(1 day to 59 years), involving 19 different subtypes.Mucopolysaccharidosis(MPS) was the most common type among LSDs, with a frequency of 45.46%(691/1 520), followed by sphingolipidoses [33.88%(515/1 520)] and glycogen storage disease type Ⅱ [16.05%(244/1 520)] successively.MPS Ⅱ was the most common type in MPS, with a frequency of 45.73%(316/691), followed by MPS ⅣA [22.87%(158/691)]. Niemann-Pick A/B, Gaucher, and Krabbe diseases were common in Sphingolipidoses patients, with frequencies of 37.09%(191/515), 34.37%(177/515), and 10.29%(53/515), respectively.Conclusions:LSDs are common genetic metabolic diseases, especially MPS and sphingolipidoses.Newborn screening for LSDs should be carried out timely so that the patients can be treated early and their prognosis can be improved.
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Precancerous lesions of gastric cancer (PLGC) is a pathological change accompanied by intestinal metaplasia and dysplasia on the basis of chronic atrophic gastritis. It is also an important stage of "inflammation-cancer transformation" on gastric mucosa. Paying attention to the intervention of PLGC has important value and significance for the secondary prevention of gastric cancer. PLGC has the characteristics of occult onset, toxin damaging collaterals, and long course of disease, which is highly consistent to the pathogenesis characteristics of incubative pathogenic factors. Based on the relevance of incubative pathogenic factors and PLGC, treatment of PLGC from the perspective of incubative pathogenic factors should be mainly strengthening the spleen and stomach, and combined with the methods of regulating qi and dissipating dampness, and removing blood stasis and detoxification. It should also pay attention to the prognosis.Paying attention to the body-mind treatment can reduce the re-occurrence , so as to provide a new way of thinking for treating PLGC from incubative pathogenic factors.
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Objective:The mechanism of Indigo Naturalis in the treatment of ulcerative colitis (UC) was predicted by GEO chip combined with network pharmacology, and preliminarily verified by molecular docking. Methods:The main active components and targets of Indigo Naturalis were obtained by searching TCMSP, SymMap database, SwissTargetPrediction and Pharmmapper. The UC disease targets were obtained from DrugBank database, OMIM database, TTD database, Disgenet database and GEO gene chips. Venn diagram was used to show drug-disease common targets. The protein-protein interaction (PPI) network of intersection targets was analyzed by String platform, and Cytoscape 3.8.2 software was used to construct the PPI network of components and disease targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the core targets. AutoDock Vina 1.2.1 was used for molecular docking, and the results were visualized by Discovery studio Visualizer. Results:A total of 10 active components and 184 compound targets of IN-UC, of which 42 were core targets, were enriched and analyzed by GO and KEGG. The therapeutic effect of Indigo Naturalis on UC may involve activation of various process, such as reactive oxygen species metabolism, heme binding, protein phosphatase binding, secretory granule exocytosis, cytoplasmic vesicles, cell focal adhesion and cell substrate connection, and regulates PI3K/Akt signal pathway, human cytomegalovirus infection signal pathway, EB virus infection signal pathway HF1 signaling pathway and insulin resistance signaling pathway to treat UC. Conlusion:Indigo Naturalis has the characteristics of multi-component, multi target and multi pathway in the treatment of ulcerative colitis. Through PTGS2, CAT and other core targets, it can regulate PI3K/Akt signal pathway, human giant cell signal pathway, HIF-1 signal pathway to play a therapeutic role.
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ObjectiveTo explore the association between daily executive function and core symptoms， the symptoms of attention deficit hyperactivity disorder （ADHD） in children with autism spectrum disorder （ASD）， and the moderating effect of theory of mind and other cognitive abilities on this association. MethodsChildren aged 6-12 years with ASD were recruited， and 86 children were identified according to the inclusion and exclusion criteria. Wechsler Intelligence Test for Children， Fourth Edition （WISC-Ⅳ）， Strange Story Test （SST） and Behavior Rating Inventory of Executive Function （BRIEF） were used to evaluate children's cognitive ability. Swanson Nolan and Pelham-Version Ⅳ Scale （SNAP-Ⅳ）， Social Responsiveness Scale （SRS）， and Repetitive Behavior Scale-Revise （RBS-R） were used to assess the severity of ADHD symptoms， social impairment， and repetitive stereotyped behavior. Multiple linear regression was used to explore the association between daily executive function and ADHD symptoms， social impairment， repetitive stereotyped behaviors. ResultsAfter controlling for the score of strange stories， verbal comprehension index （VCI） and other factors， the full scale score and each index of BRIEF were positively correlated with full scale score of SNAP （b = 0.619-0.741， b’ = 0.637-0.755）， SRS （b = 0.928-1.200， b’ = 0.417-0.513） and RBS-R （b = 0.326-0.525， b’ = 0.339-0.520） in children with ASD （P< 0.05）， and the SNAP total score was more strongly correlated with the full scale BRIEF score and each index score （b’ = 0.637-0.755，P< 0.01）. In addition to daily executive function， strange stories score （b = -2.218- -1.839） and age （b = 3.181-4.037） were also the important factors affecting the social function of children with ASD （P< 0.01）. There were no moderating effects of strange stories score and age on the association between BRIEF score and full scale score of SNAP， SRS， and RBS-R（P> 0.05）. ConclusionThe deficits of daily executive function in school-aged ASD children are significantly associated with core symptoms and ADHD symptoms， and the association is independent of other cognitive domains， such as theory of mind and verbal comprehension intelligence quotient.
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Aim To investigate the effect of PI3K/AKT/NF-κB signaling pathway in the treatment of physicion-8-O-β-D-monoglu-coside(PMG) on acute liver injury induced by carbon tetracloride(CCl 4) in mice . Methods Mice were randomly assigned into control group, model group, PMG low-dose, medium-dose and high-dose groups and Bifendate groups. After the continuous intervention with PMG for three days, CCl 4oil solution was intraperitoneally injected to establish acute liver injury mouse models, and samples were collected sixteen hours later. HE staining was used to observe the pathological changes of liver tissue. Hoechst 33342 staining was used to detect the number of apoptotic hepatocytes. Western blot was employed to detect the expression levels of caspase-3, PI3K, p-PI3K, AKT, p-Akt, IκB, p-IκB total protein and the nuclear protein NF-κB p65 in mouse liver tissue. The proportion of Th17 cells in mouse liver tissue was detected by FACS. Results After three days of PMG treatment, the pathological injury of liver tissue was relieved, the apoptosis of liver cells and the protein levels of caspase-3(P<0.01) were induced compared with model group.PMG could significantly decrease the nuclear expression of NF-κB p65 in the liver of mice with acute liver injury(P<0.05 or P<0.01). The phosphorylation levels of PI3K, AKT and IκB significantly decreased by PMG(P<0.05 or P <0.01). Otherwise, the proportion of Th17 cells in liver tissue was significantly reduced after PMG treatment(P<0.01). Conclusion PMG can alleviate CCl4 - induced acute liver injury through PI3K/AKT/NF-κB signaling pathway.
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OBJECTIVE@#To explore the molecular mechanisms of Porphyromonas gingivalis infection-induced umbilical vein endothelial barrier dysfunction in vitro.@*METHODS@#Human umbilical vein endothelial cells (HUVECs) were cultured in vitro, and after the formation of the endothelial barrier, the cells were infected with P. gingivals at a multiplicity of infection (MOI). The transepithelial electrical resistance (TEER) of the cell barrier was measured, and FITC-dextran trans-endothelial permeability assay and bacterial translocation assay were performed to assess the endothelial barrier function. The expression levels of cell junction proteins including ZO-1, occludin and VE-cadherin in the cells were examined by qRT-PCR and Western blotting.@*RESULTS@#In freshly seeded HUVECs, TEER increased until reaching the maximum on Day 5 (94 Ωcm2), suggesting the formation of the endothelial barrier. P. gingivals infection caused an increase of the permeability of the endothelial barrier as early as 0.5 h after bacterial inoculation, and the barrier function further exacerbated with time, as shown by significantly lowered TEER, increased permeability of FITC-dextran (40 000/70 000), and increased translocation of SYTO9-E. coli cross the barrier. MTT assay suggested that P. gingivals infection did not significantly affect the proliferation of HUVECs (P>0.05), but in P. gingivalsinfected cells, the expressions of ZO-1, occludin and VE-cadherin increased significantly at 24 and 48 h after bacterial inoculation (P < 0.05).@*CONCLUSION@#P. gingivals may disrupt the endothelial barrier function by down-regulating the expressions of the cell junction proteins (ZO-1, occludin, VE-cadherin) and increasing the permeability of the endothelial barrier.
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Humans , Cadherins/metabolism , Escherichia coli/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Occludin , Porphyromonas gingivalis/metabolism , Umbilical Veins/metabolismABSTRACT
OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with Rubinstein-Taybi syndrome (RSTS).@*METHODS@#A child who was admitted to the Children's Hospital of Soochow University on October 3, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing of his family members and bioinformatic analysis.@*RESULTS@#The patient, a 9-year-and-４-month-old boy, had manifested unique facies, microcephaly, broad toes, growth retardation, and intellectual impairment. WES revealed that he has harbored a heterozygous c.3604G>T (p.E1202*) variant in exon 20 of the EP300 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant was not found in the Shenzhou Genome data Cloud, ExAC, 1000 Genomes and gnomAD databases．Analysis with SIFT, PolyPhen-2 and CADD online software has predicted the variant to be harmful. Based on the guidelines formulated by the American College of Medical Genetics and Genomics, the variant was rated as pathogenic (PVS1＋PS2＋PM2_Supporting) .@*CONCLUSION@#The heterozygous c.3604G>T variant of the EP300 gene probably underlay the RSTS type 2 in this child. Above finding has also expanded the variation spectrum of the EP300 gene.