The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

Objective:To investigate the dynamic expression of DNA damage repair protein Nijmegen breakage syndrome protein 1(NBS1) in the neonatal rats with bronchopulmonary dysplasia(BPD), and its influence on the development and progression of BPD.Methods:Newborn rats were randomly divided into the BPD model group( n=50) and the control group( n=50) within 12 h after birth.The inhaled oxygen concentration was 80%-85% in the model group, and the control group inhaled air.In the two groups, lung tissue samples were collected on days 1, 3, 7, 10 and 14, and isolated, purified and cultured alveolar epithelial type Ⅱ cells(AEC Ⅱ). We observed pulmonary morphological changes under light microscope and evaluated alveolar development degree by radiate alveolar counts(RAC). Immunohistochemistry and cell immunofluorescence were used to observe the localization and expression of NBS1.Western blot and real-time quantitative PCR were used to detect the expression level of NBS1. Results:Compared with the control group, the RAC value in the model group was decreased significantly from 7 d after birth(control group 7.58±1.24, model group 5.42±1.24, P<0.01). Immunohistochemistry showed that NBS1 protein was mainly located in the nucleus of alveolar epithelial cells.In the model group, NBS1 was mainly expressed in the nucleus on the 1st day.With the prolonged exposure time, the number of cytoplasmic staining cells increased and the expression in the nucleus decreased.Cell immunofluorescence farther showed that NBS1 protein was mainly located in the nucleus in AEC Ⅱ.Compared with the control group, cytoplasmic staining in model group was enhanced from 3 d, while nuclear staining was gradually weakened, and was mainly located in the cytoplasm at 14 d. Western blot results showed that the expression of NBS1 protein in the model group peaked at 1 d compared to the control group(control group 0.72±0.29, model group 1.28±0.22, P<0.01), and then gradually decreased, with lower expression at 14 d compared to the control group(control group 0.73±0.19, model group 0.49±0.11, P<0.05). Similarly, the mRNA expression level of NBS1 in the model group peaked at 1 d compared to the control group(control group 1.00±0.00, model group 1.18±0.06, P<0.01), and then gradually decreased, with lower expression at 14 d than that in the control group(control group 1.07±0.13, model group 0.76±0.11, P<0.05). Conclusion:In the neonatal rats with BPD, the down-regulation expression and nuclear enrichment disorder of NBS1 may affect the DNA damage response and be one of the mechanisms mediating the onset of oxidative stress damage in BPD.

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Objective:To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen.Methods:From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin′an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ 2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results:The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [ OR (95% CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [ OR (95% CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [ OR (95% CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion:The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

Objective:To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen.Methods:From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin′an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ 2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results:The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [ OR (95% CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [ OR (95% CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [ OR (95% CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion:The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

Objective To investigate the association between serum 25(OH) D levels and the inci-dence of early-onset sepsis(EOS) in the very low birth weight infants(VLBWI) and the gestational age be-low 34 weeks. Methods The cord blood of 159 VLBWI were collected between January and December 2017,including 31 clinically diagnosed EOS and 128 non-EOS patients. Serum 25(OH)D<10 ng/ml was de-fined as severe vitamin D deficiency,25(OH)D 10 to 20 ng/ml as vitamin D deficiency,25(OH)D 20 to 30 ng/ml as vitamin D insufficiency and 25(OH)D >30 ng/ml as vitamin D sufficiency. Results There were no differences in gender,gestational age,birth weight and Apgar score between the EOS group and the non-EOS group(P>0. 05). Serum 25(OH) D was(9. 08 ± 4. 21) ng/ml in the EOS group and(11. 91 ± 5. 37) ng/ml in the non-EOS group(P＝0. 007). The rate of severe vitamin D deficiency was 67. 7%(21/31)in the EOS group and 41. 4%(53/128) in the non-EOS group. The rate of vitamin D deficiency was 32. 3%(10/31)in the EOS group and 52. 3%(67/128)in the non-EOS group. But there was no difference of vitamin D deficiency distribution in the two groups(P＝0. 152). The cut-off value of serum 25(OH)D level in predic-ting EOS was 10. 06 ng/ml. Conclusion The incidence of vitamin D deficiency is as high as 95%,calling for urgent attention on vitamin D supplementation in those VLBWI. Low 25(OH)D level( <10 ng/ml)might be predictive of EOS.

Aim Drug repositioning is to find new indications for existing drugs,however,potential drug-disease relationships are often hidden in millions of unknown relationship.With the analyzing of medical big data,we predict the potential drug-dis-ease relationships.Methods Based on the assumption that similar drugs tend to have similar indications,we applied a rec-ommendation-based strategy to drug repositioning.First,we col-lected the information of known drug-disease therapeutic effect, side effect,drug characters and disease characters;second,we calculated the drug-drug similarity measurements and disease-disease similarity measurements;last,we used a collaborative filtering (CF)method to predict unknown drug-disease relation-ships based on the known drug-disease relationships by integra-ting the similarity measurements,and built a ranking list of pre-diction results.Results The experiments demonstrated that a-mong the TOP 500 of the list,1 2.8% were supported by clinical experiments or review,and 20% were supported by model or-ganism or cell experiments.Conclusion Compared to the clas-sification model and random sampling results,the CF model can effectively reduce the false positives.

Objective To investigate the correlation between brain injury and premature infants with bronchopulmonary dysplasia (BPD)and to analyze the risk factors of brain injury in premature infants with BPD based on MRI changes.Methods A total of 1 13 premature infants diagnosed with BPD were studied as case group from January 2010 to December 2014 at the neonatal ward of Shengjing Hospital of China Medical University.One hundred and sixty-two premature infants without BPD were selected as control group.There were no significant differences in gestational age and birth weight between the two groups.All cases were per-formed MRI examination in hospital.The occurrence of brain injuries(white matter injury and intracranial hemorrhage)were compared based on MRI changes between the two groups,and the risk factors of brain in-jury in case group were analyzed.Results The case group and control group were performed MRI on (33.73 ±16.00)d,(24.40 ±12.29)d after birth respectively.The ratio of brain injury,intracranial hemor-rhage,cerebral white matter damage and severe brain injury of case group was higher than those of the control group(48.7% vs.32.7%,3 1.9% vs.21.6%,31.9% vs.21.6%,16.8% vs.8.6%,respectively).The differences were significant in the ratio of brain injury and severe brain injury (P =0.008,P =0.040,respec-tively).Logistic regression analysis showed that postnatal infection was a risk factor for brain injury of the case group(OR =2.21 ,95%CI 1.04 ~4.72,P ﹤0.05).Conclusion More brain injury(including the white matter injury and intracranial hemorrhage)and severe brain injury(including grade III ~IV intraventricular hemorrhage and periventricular leukomalacia)are detected in premature infants with BPD.Postnatal infection is a risk factor of brain injury for premature infants with BPD.

Objective To investigate the early MRI performance and the evolution of premature infants who developed into periventficular leucomalacia (PVL) eventually.Methods Twelve premature infants diagnosed as PVL by MRI in the department of neonatology in Shengjing Hospital of China Medical University from Jan 2010 to Dec 2013 were selected,all of the cases underwent conventional MRI and diffusion-weighted imaging (DWI) examination twice,the first examinations were finished in 2 to 7 days (mean 5.5 d) after birth and the second examinations were taken in 17 to 23 days(mean 20.3 d).Results The first examination showed:all cases performed high signal intensity of periventricular matter,including 6 diffuse and symmetrical,3 linear and 3 clustered high signal.However,only 5 of the 12 cases showed slightly high signal on T1 weighted image with low signal on T2 weighted image on conventional MRI,the other 7 cases showed no change;for the reexamination:foci of different numbers and sizes showed up in all cases,with the performance of low signal on T1 weighted image,high signal on T2 weighted image and low signal on DWI correspondingly.Conclusion DWI is superior to conventional MRI in finding and forecasting PVL;diffuse white matter damage have more probability to develop into PVL,severe local white matter damage such as multi-clustered and linear damage also can develop into PVL.