Telmisartan loading thermosensitive hydrogel repairs gut epithelial barrier for alleviating inflammatory bowel disease.

Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.

Hedscandines A-C, three undescribed indole alkaloids from Hedyotis scandens with their anti-MRSA activity.

Hedscandines A-C (1-3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 µg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death.

Acupuncture combined with pelvic floor rehabilitation training for postpartum stress urinary incontinence: protocol for a systematic review and meta-analysis.

Introduction: The purpose of this study is to systematically evaluate the efficacy and safety of acupuncture combined with pelvic floor rehabilitation training in the treatment of postpartum stress urinary incontinence, and to promote the further promotion and application of acupuncture in the field of rehabilitation. Methods and analysis: Randomized controlled trials (RCTs) of acupuncture combined with pelvic floor rehabilitation in the treatment of postpartum stress urinary incontinence will be searched in PubMed, Web of Science (WOS), Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang (WF), and VIP databases. The clinical trial Registry (ClinicalTrials.gov and Chinese clinical trial Registry) will also be searched. The search period is limited to July 1, 2023, and the language limit of this systematic review is Chinese and English. The primary outcome is clinical effective rate. International Consultation on Incontinence Questionnaire-Short Form (ICI-Q-SF), 1-h pad test, pelvic floor muscle potential value, incidence of adverse events are secondary outcomes. A meta-analysis will be performed using RevMan 5.4 statistical software. If feasible, subgroup analysis and sensitivity analysis will be performed to address potential causes of inconsistency and heterogeneity. The risk of bias will be assessed using the approach recommended by Cochrane Handbook for Systematic Reviews of Interventions, and the quality of evidence will be assessed using GRADE. This Protocol has been developed in accordance with the guideline of Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015. Discussion: Acupuncture combined with pelvic floor rehabilitation training can effectively promote the rehabilitation of postpartum stress urinary incontinence patients, and provide a reference for the clinical application of integrated Chinese and Western medicine treatment in the field of rehabilitation. Systematic review registration: PROSPERO CRD42023455801.

circAP1M2 activates ATG9A-associated autophagy by inhibiting miR-1249-3p to promote cisplatin resistance in oral squamous cell carcinoma.

Cisplatin (CDDP) is the first-line chemotherapeutic agent for oral squamous cell carcinoma (OSCC). Susceptibility to drug resistance during treatment is a significant challenge in enhancing the therapeutic efficacy of OSCC. Autophagy is an essential element to guarantee the cancer cells' survival under chemo-stress conditions. We established a cisplatin-resistant OSCC cell line (CAL27/CDDP) and showed that circAP1M2 is a remarkably upregulated circular RNA in OSCC. Knockdown of circAP1M2 contributes to reversing cisplatin chemoresistance in vivo, while enhanced autophagic activity in cisplatin-resistant OSCC cells contributes to chemoresistance. Mechanistically, we showed that circAP1M2 induces autophagy-associated cisplatin resistance via the miR-1249-3p-ATG9A axis in OSCC cells. This study provides insights into the specific influence of a newly identified circular RNA circAP1M2 in OSCC regarding drug abuse and the treatment of a broad range of cancers that can benefit from cisplatin.

Individual and dyadic network analyses of depressive symptoms in Chinese postpartum couples: A cross-sectional study.

BACKGROUND: The network approach to psychopathology is symptom oriented and may open new possibilities for intervention development and health care practices in postpartum depression. OBJECTIVE: To investigate the individual and dyadic symptom network of postpartum depression in Chinese mothers and fathers in the very early postpartum period. DESIGN: A cross-sectional study was conducted. SETTINGS AND PARTICIPANTS: A total of 457 couples in the 2∼3 days postpartum period was recruited consecutively from a hospital in Guangzhou, China from September 2020 to April 2021. METHODS: The Edinburgh Postnatal Depression Scale and socio-demographic and obstetric data sheet were used to collect data. We estimated the individual symptom networks of postpartum mothers and fathers separately and a dyadic symptom network that consisted of symptoms of both spouses. Network characteristics including global strength and node centralities were analyzed and systematically compared. RESULTS: Strength centralities in the individual networks showed acceptable stability [Correlation stability coefficient (CS) for mothers = 0.60; CS for fathers = 0.52]. The central depressive symptoms in mothers were Crying (Zstrength = 1.32), Overwhelmed (Zstrength = 1.01) and Sad mood (Zstrength = 0.93). The central depressive symptom in fathers was Sad Mood (Zstrength = 1.35). The symptom "Crying" had a distinctive link to thoughts of self-harm in fathers. The symptom network of mothers (global strength = 4.15) was more interconnected than that of fathers (global strength = 3.74). There was a statistically significant but unstable within-couple connection of thoughts of self-harm (CS = 0.21). CONCLUSIONS: Postpartum mothers are more vulnerable to activation spreads of depressive symptoms than postpartum fathers. Symptoms including "Sad mood", "Overwhelmed" and "Crying" warrant the attention of health care providers. Investigations with larger sample sizes and gender-sensitive instruments are needed to further unfold the individual and dyadic symptom dynamics of postpartum depression.

Research progress on the role and mechanism of premature cellular senescence on wound healing in radiation-induced skin injury / 中华放射医学与防护杂志

Radiation skin injury can be induced by medical exposure, occupational exposure, and emergency exposure. Many relevant studies focused on the prevention and treatment of radiation-induced skin injury, but the underlying molecular mechanisms have not been fully clarified. It has been demonstrated that radiation-induced premature cellular senescence is involved in radiation skin injury. To discuss the relationship between radiation-induced premature cellular senescence and radiation-induced skin injury, this paper reviewed the mechanism of radiation-induced skin injury, the promotion of premature cellular senescence and related signal pathways, and the role of premature cellular senescence in wound healing.

The mediating effect of resilience on anxiety and subjective well-being in occupational population / 中华劳动卫生职业病杂志

Objective: To explore the current situation of anxiety, subjective well-being in occupational population and the mediating effect of resilience. Methods: From March 24th to 26th, 2020, a cross-sectional survey was conducted among occupational population aged ≥18 years old using online questionnaires. A total of 2134 valid questionnaires were obtained, with respondents from 30 provinces, autonomous regions, and municipalities directly under the Central Government. Their general demographic data, subjective well-being, anxiety, and resilience were collected. Pearson χ(2) test and Spearson correlation analysis were used for data analysis, and structural equation model was used to explore the mediating effect of resilience on anxiety and subjective well-being. Results: The age of the respondents ranged from 18 to 60 years old, with an average age of (31.19±7.09) years old, including 1075 (50.4%) women and 1059 (49.6%) men. The positive rates of low subjective well-being and anxiety were 46.5% (992/2134) and 28.4% (607/2134), respectively. Anxiety scores were significantly negatively correlated with subjective well-being scores and resilience scores (r(s)=-0.52, -0.41, P<0.05), while resilience was significantly positively correlated with subjective well-being (r(s)=0.32, P<0.05). Structural equation models showed that anxiety had a negative predictive effect on subjective well-being, while resilience not only had a positive predictive effect on subjective well-being, but also played a mediating role between anxiety and subjective well-being, with a mediating effect of 9.9%. Conclusion: The situation of anxiety and well-being in the occupational population is still not optimistic, and resilience has a mediating effect between anxiety and subjective well-being.

Research progress of RNA drugs delivery / 药学学报

Ribonucleic acid (RNA) medicines have strong therapeutic potential for numerous rare genetic illnesses and malignancies because of its exact programmability based on Watson-Crick base pairing principle and unique ability to regulate gene expression. However, RNA medicines still have limitations in many areas, including stability, half-life time, immunogenicity, organ selectivity, cellular uptake and endosomal escape efficiency despite their great therapeutic potentials. This review briefly introduced numerous RNA medications [mostly messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) and antisense oligonucleotide (ASO)] that have intrigued of researchers in recent years, as well as their action mechanism in vivo. A number of delivery techniques, such as chemical modification, ligands coupling and nanocarriers have been proposed. The manufacture and applications of lipid nanoparticle, polymer nanoparticle and exosomes were discussed in depth. The goal of this work is to give a theoretical foundation and design concepts for the development of effective and safe RNA delivery technology, as well as to facilitate RNA therapeutic clinical translation.

Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72 h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

The Characteristics of T Lymphocyte Reconstitution after Haploid Hematopoietic Stem Cell Transplantation in SAA and Its Relationship with aGVHD / 中国实验血液学杂志

OBJECTIVE@#To investigate the recovery characteristics of T cell subsets in patients with severe aplastic anemia (SAA) who received haploid hematopoietic stem cell transplantation(HSCT) and its relationship with acute graft-versus-host disease(aGVHD).@*METHODS@#The clinical data of 29 SAA patients who received haploid hematopoietic stem cell transplantation in the department of hematology, Shanxi Bethune Hospital from June 2018 to January 2022 were retrospectively analyzed. The absolute counts of CD3+T, CD4+T, CD8+T lymphocytes and the ratio of CD4+T/CD8+T lymphocytes in all patients before transplantation, 14, 21, 30, 60, 90 and 120 days after transplantation were analyzed. The proportion of T lymphocytes was compared in the non-aGVHD group, the grade Ⅰ-Ⅱ aGVHD group and the grade III-IV aGVHD group.@*RESULTS@#The counts of all T cells in 27 patients were far below the normal level at 14 and 21 days after transplantation, but there was obvious heterogeneity. There was a certain relationship between T cell immune reconstitution and conditioning regimen, age, and immunosuppressive treatment before transplantation. CD3+T cells showed a steady upward trend at 30, 60, 90, and 120 days after transplantation, and returned to the normal levels at 120 days after transplantation; faster recovery of CD4+T cells was closely related to aGVHD, which was at 30, 60, 90, 120 days after transplantation showed a slow upward trend, and which was still far below the normal level of 120 days after transplantation. CD8+T cell counts began to recover at 14 and 21 days after transplantation, and the recovery was earlier than the CD4+T cells, and its recovery speed was rapid 30 and 60 days after transptantation, which showed an upward trend and exceeded the normal levels 90 days after transplantation. Since CD8+ T cells reconstituted quickly, while the CD4+ T cells reconstitution was slowly, which made the long-term CD4+T/CD8+T cell ratio after transplantation was inverted . Compared with the non-aGVHD group, the absolute counts of CD3+T, CD4+T, and CD8+T cells in the aGVHD group were significantly higher than those in the non-aGVHD group at each time period after transplantation. In the aGVHD group, grade Ⅲ-Ⅳ aGVHD occurred more frequently in the early post-transplantation period (within 14-21 days), the grade Ⅰ-Ⅱ aGVHD group mostly occurred within 30-90 days after transplantation, and CD3+T, CD4+T, CD8+T cell counts in the grade Ⅲ-Ⅳ aGVHD group were significantly higher than those in the grade Ⅰ-Ⅱ aGVHD group; and the greater the proportion of CD4+T, the more severe the degree of aGVHD.@*CONCLUSION@#The speed of T cell immune reconstitution after SAA haploid transplantation is different, which is related to the conditioning regimen, age, and immunosuppressive therapy before transplantation. The rapid recovery of CD4+ T cells is closely related to the occurrence of aGVHD.

Establishment of a risk model for severe adenovirus pneumonia and prospective study of the timing of intravenous immunoglobulin therapy in children / 中国当代儿科杂志

OBJECTIVES@#To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP.@*METHODS@#Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment.@*RESULTS@#Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (P>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (P<0.05).@*CONCLUSIONS@#The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.

The Experience Among College Students with Social Anxiety Disorder in Social Situations: A Qualitative Study.

Background: Few individuals have focused on the experience of students during social events, especially among college students with social anxiety disorder. This study aimed to explore the anxiety experience among college students with social anxiety disorder in social situations. Methods: This qualitative interpretive study was conducted on college students who were diagnosed with social anxiety disorder (SAD) and recruited from two colleges in Heilongjiang Province, China. A total of 7 participants were selected by purposive sampling with maximum variability. Data were collected through semistructured individual interviews, and data analysis was performed by using Colaizzi's 7-step analysis method. Results: The findings from the analysis of the interviews were classified into 4 themes and several main categories, including distorted self-awareness (3 main categories), fear of negative reaction from others (2 main categories), adverse reaction of body and mind (4 main categories) and strong desire to seek treatment. Conclusion: In our study, we sought to understand the anxiety experience among college students with social anxiety disorder in social situations. The study results provide a reference for psychologists and clinical medical staff and establish a scientific basis for the prevention and intervention of social anxiety disorder.

Asymmetric and time-varying linkages between carbon emissions, globalization, natural resources and financial development in China.

In the real world, economic covariates follow asymmetric and time-varying patterns. Therefore, it is imperative to integrate these effects while estimating environmental and economic relationships. Although prevailing literature reveals various emissions-deriving and eliminating factors, however, there is a dearth of empirical evidence that estimates the asymmetric and time-varying effect of globalization, natural resources, and financial development from a multidimensional perspective in China. In doing so, we employ the nonlinear autoregressive distributed lag (NARDL) and cross-wavelet modeling framework to explore the long- and short-run nonlinear and time-variant association between globalization, natural resources, financial development, and carbon emissions from 1980 to 2017. The NARDL method has the benefit of discriminating the long-term and short-term asymmetric carbon emission responses due to a positive and negative shock in our primary variables of interest. Mainly, the findings of NARDL estimations confirm that positive shocks in globalization and financial developments have a significant positive impact on carbon emissions, whereas negative shock in natural resources has a significant positive impact on carbon emissions. Similarly, the outcomes of continuous wavelet transformation and wavelet transformation coherence confirm the causal linkages between covariates; however, this effect varies across different time and frequency domains. These results imply that environmental researchers should consider asymmetric transmission channels and time-frequency associations among variables to devise long-term sustainable policies.

Changes of gut microbiota and its effect on glucose tolerance in a novel mice model of insulin resistance (eLtaS trans) / 中华内分泌代谢杂志

Objective:To investigate the correlation between insulin resistance and alterations in gut microbiota using the animal model of insulin resistance(eLtaS transgenic mice).Methods:Glucose tolerance was measured in eLtaS trans mice and wild-type (WT) mice. Faecal samples of mice were collected for metagenomics and 16S rDNA sequencing. Alterations of gut microbiota in eLtaS trans mice were further analyzed. Faeces from eLtaS trans mice were transplanted into WT mice by " dirty cage" sharing experiment, and glucose tolerance of mice was measured at different time points after transplantation. Results:Significant differences in composition and function of gut microbiota were observed between eLtaS trans mice and WT mice( P=0.028). Compared with WT mice, the diversity of gut microbiota in eLtaS trans mice increased evidently, moreover the relative abundance of Phylum Firmicutes in eLtaS trans mice significantly increased( P<0.001). However, the relative abundance of Phylum Bacteroides and Phylum Verrucomicrobia decreased visibly( P=0.042, P=0.033). The relative abundance of Akkermansia muciniphila and Parabacterides distasonis related to metabolic diseases decreased significantly in eLtaS trans mice( P=0.033, P=0.013). The gut microbiota of eLtaS trans mice was clearly different from that of WT mice in carbohydrate metabolism, lipid metabolism, biosynthesis of other secondary metabolites, metabolism of other amino acids, energy production and transformation. The glucose tolerance of WT mice was impaired at 7th, 8th and 9th week after faecal transplantation, and recovered at 1 week after cessation of faecal transplantation. Conclusion:Insulin resistance leads to obvious changes of gut microbiota in mice, meanwhile the gut microbiota of insulin resistance mice can further induce impaired glucose tolerance.

Mechanism of the influence of CPT1 on the proliferation of rat intestinal epithelial cells IEC-6 after 60Co γ-ray irradiation / 中华放射医学与防护杂志

Objective:To investigate the changes of CPT1A and CPT1B protein expression in rat intestinal epithelial cells (IEC-6) after 60Co γ-ray irradiation, and the mechanism of the influence of carnitine palmitoyltransferase 1 (CPT1) on the proliferation of irradiated IEC-6 cells. Methods:IEC-6 cells were cultured in serum-normal medium or in serum-starved medium overnight, and pretreated with 20 μmol/L palmitic acid (PA) before irradiation with 0, 5, 10, and 15 Gy. At 24 h after irradiation, the cellular protein was collected for the measurement of CPT1A and CPT1B proteins by Western blot. The influences of ETO, an inhibitor of CPT1, on the survival and proliferation of irradiated IEC-6 cells were analyzed by colony formation assay and CCK-8 assay. The protein expressions and phosphorylation levels of the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) in 5 Gy irradiated IEC-6 cells pre-treated with ETO were analyzed by Western blot at 48 h after radiation.Results:When IEC-6 cells were cultured in serum-normal medium together with PA, the protein level of CPT1A was significantly increased after 15 Gy irradiation ( t=-2.82, P<0.05). When IEC-6 cells were cultured in serum-starved medium, the protein level of CPT1A was significantly increased at 5, 10, and 15 Gy ( t=-3.28, -8.72, -8.67, P<0.05). When IEC-6 cells were cultured in serum-starved medium together with PA, the protein levels of CPT1A were significantly increased at 5, 10 and 15 Gy ( t=-10.69, -7.02, -8.23, P<0.05), the protein levels of CPT1B were significantly increased at 10 and 15 Gy ( t=-3.73, -5.05, P<0.05). After irradiation, the survival and proliferation of IEC-6 cells in ETO group were significantly lower than those in control group ( t=5.46, 13.22, P<0.05), and the protein level of ERK1/2 and p-JNK in ETO group were significantly lower than those in control group ( t=4.01, 3.29, 10.68, 14.44, P<0.05). Conclusions:CPT1 promoted radiation-induced IEC-6 injury cells survival and proliferation by enhancing the expression level of ERK1/2 protein and the activity of JNK.

Clinical application of dense fine spot anti-nuclear antibody in children with autoimmune diseases / 中华实用儿科临床杂志

Objective:To analyze the differences of the clinical characteristics and laboratory indexes in children with positive dense fine spot (DFS) type anti-nuclear antibody, and thereby to explore the value of positive DFS in the diagnosis of immunological diseases.Methods:Among 9 613 cases who were routinely tested for antinuclear antibody (ANA) from August 2017 to February 2020, there were 197 cases with DFS positive, who were subjected to a retrospective analysis.These patients were divided into the autoimmune diseases (AID) group (39 cases) and the non-AID group (158 cases) according to clinical diagnosis.Healthy children in the same physical examination were used as healthy control group (40 cases). T test was applied to analyze the differences of humoral immunity markers between AID and non-AID groups.What′s more, DFS positive patients in different clinical departments, initial symptom and the part of body were further compared. Results:Among 9 613 children tested for autoantibodies, 2 654 (27.61%) were ANA positive, with the highest detection rate of the spotted type and 197 DFS positive cases, accoun-ting for 7.42% of ANA positive children; 97 DFS positive male patients accounted for 8.20% (97/1 183 case) of ANA positive male patients, 100 DFS positive female patients accounted for 6.80% (100/1 471 cases) of ANA positive female patients, and there was no significant difference in the positive rate.The departments with high positive ANA detection included the nephrology department (27.88%) and the rheumatology department (24.83%). The departments with a higher ANA positive rate in DFS positive children included the gastroenterology department (13.25%) and the infectious department (11.76%). Among the children with DFS antibody positive, 39 cases had AID, among which 38 cases had organ-specific AID, and juvenile idiopathic arthritis (JIA) had the highest detection rate in 13 cases.The diseases with a high DFS positive rate in 158 non-AID cases included allergic purpura (46 cases). Serum immunoglobulin (IgG) level in the AID group was significantly lower than this in the non-AID group, serum IgM and C 4 levels in AID children were significantly lower than those in the non-AID group and healthy control group, and the serum IgA level of DFS positive group was significantly higher than that of children in the healthy control group.All children with DFS antibody positive had no specific autoantibodies. Conclusions:DFS antibody positive is important for the diagnosis of systemic AID in children.The combined detection with the DFS, other autoimmunity antibody index, humoral immune function index contributes to the early differential diagnosis of autoimmune diseases in children.

Discussion on Design of Comprehensive Verification and Evaluation Schemes for Electrocardiogram Medical Electronic Instruments / 中国医疗器械杂志

This study introduced the current testing content and standards of ECG medical electronic instruments, combined with actual clinical needs, and discussed the comprehensive verification and evaluation protocol for ECG medical electronic instruments. The protocol mainly includes hardware performance testing, automatic diagnostic function testing and clinical application evaluation. The protocol emphasizes the clinical practicality and importance of the comprehensive verification and evaluation program, and provides a reference for the institutions involved in the program.

Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation / 中华内科杂志

Objective:To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily.Methods:The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test.Results:A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively ( P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively ( P<0.001, P=0.001). Conclusion:The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

Reducing neuroinflammation and improving neurobehavioral functions: the protective roles of resveratrol for germinal matrix hemorrhage in neonatal rat model / 中国新生儿科杂志

Objective:To study the roles of resveratrol in reducing neuroinflammation and improving neurobehavioral functions after germinal matrix hemorrhage (GMH) in neonatal rat model.Methods:GMH model was established intraparenchymally injecting bacterial collagenase in 7-day-old SD rats. 108 rats were randomly assigned into 18 groups (6 in each group), including 4 sham groups, GMH (12 h, 24 h, 72 h, 7 d) groups, 3 GMH+vehicle (dimethylsulfoxide, DMSO) groups, 5 GMH+resveratrol (10 mg/kg, 100 mg/kg, 1 000 mg/kg) groups and 2 GMH+resveratrol+EX527 (SIRT1 inhibitor) groups. Negative geotaxis and righting reflex tests were used to evaluate the short-term neurobehavior. Water maze, foot fault and Rotor-Rod tests were used to assess the long-term neurobehavior. Immunofluorescence was used to quantify the IL-1β and MPO positive cells (inflammatory markers) in peri-hematoma area. Western blot was used to evaluate the expression of relevant proteins in the brain.Results:Endogenous sirtuin-1(SIRT1) decreased to the lowest level at 24 h and then increased gradually. Phosphorylated NF-κB increased at 12 h, peaked at 72 h and returned to normal level at 7 d after GMH. Compared with the control group and other doses groups, GMH treated with resveratrol (100 mg/kg) had higher short-term behavioral scores at 48 h and 72 h. Compared with the control group, the resveratrol (100 mg/kg) group also had higher scores in water maze, foot fault and Rotor-Rod tests 22 days later. Immunofluorescence showed less positive IL-1β and MPO cells around hematoma in GMH+resveratrol group than both GMH+vehicle group and GMH+resveratrol+EX527 group. Western blot indicated that IL-1, TNF-α and IL-6 expressions were decreased in GMH+resveratrol group and Ex527 could offset the effects of resveratrol.Conclusions:Resveratrol (optimal dose: 100 mg/kg) can improve the short-term and long-term neurobehavioral functions of neonatal GMH rats. It can reduce GMH cells with positive inflammatory markers around the hematoma, possibly via inhibition of the SIRT1/NF-κB pathway. Resveratrol may be promising for the treatment of GMH patients.

Effect of herb-partitioned moxibustion in improving tight junctions of intestinal epithelium in Crohn disease mediated by TNF-α-NF-κB-MLCK pathway / 针灸推拿医学（英文版）

Objective: To explore the effect of herb-partitioned moxibustion (HPM) on tight junctions (TJs) of intestinal epithelial cells in Crohn disease (CD) mediated by tumor necrosis factor-α (TNF-α)-nuclear factor kappa B (NF-κB)-myosin-light- chain kinase (MLCK) pathway. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an HPM group and a mesalazine (MESA) group, with 12 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was administered to establish CD models. When the model was confirmed a success, the HPM group rats were treated with HPM at Tianshu (ST 25) and Qihai (CV 6), while the MESA group rats were given MESA solution by lavage. When the intervention finished, the colonic epithelial tissues were separated, purified and cultured in each group to establish the intestinal epithelial barrier model in vitro, and TNF-α was added (100 ng/mL) in the culture medium and maintained for 24 h to establish an increased epithelial permeability model. Transepithelial electrical resistance (TEER) was used to examine the permeability of the barrier; Western blot was used to observe the expressions of the proteins related to TJs of intestinal epithelial cells mediated by TNF-α-NF-κB-MLCK pathway; immunofluorescence staining was used to observe the expressions and distributions of tight junction proteins in the intestinal epithelium. Results: After TNF-α induction, compared with the MC+TNF-α group, the TEER value increased significantly in the HPM+TNF-α and MESA+TNF-α groups (both P<0.001); the expressions of nuclear factor kappa B (NF-κB) p65, MLCK, myosin light chain (MLC), tumor necrosis factor receptor-associated factor 6 (TRAF6) and receptor interaction protein-1 (RIP1) decreased significantly (P<0.01 or P<0.05), and the expression of zinc finger protein A20 (A20) increased significantly (P<0.01); the expressions of occludin, claudin-1, zonula occludens protein 1 (ZO-1) and F-actin also increased significantly (all P<0.01). Compared with the MESA+TNF-α group, the expressions of MLC, occludin, claudin-1, ZO-1 and F-actin increased significantly in the HPM+TNF-α group (P<0.01 or P<0.05). Conclusion: HPM can protect or repair the damage of intestinal epithelial barrier in CD rats, which may be achieved through modulating the abnormal TJs in intestinal epithelium mediated by TNF-α-NF-κB-MLCK pathway.