Clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 Omicron variant infection / 中华传染病杂志

Objective:To investigate the clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection in Shanghai City.Methods:A field investigation among the pediatric cases with Omicron variant infection and their household contacts from April 4 to April 30, 2022 in Children′s Hospital of Fudan University was conducted. The informations on case finding, clinical manifestations and SARS-CoV-2 vaccination status were collected. The epidemiological and clinical characteristics were compared between pediatric cases and adult cases. The independent sample t test or chi-square test was used for statistical analysis, and the relative risk ( RR) and 95% confidence interval (95% CI) were used to evaluate the protective effect of vaccination on the infection of Omicron variant. Results:There were 1 274 family members in 297 families including 370 children and 904 adults of whom 1 110(87.13%) were infected with Omicron variant, with 989(89.10%) symptomatic and 121(10.90%) asymptomatic. There were 355 children infected with Omicron variant, of whom 337(94.93%) were symptomatic, and the main manifestations were fever (96.74%(326/337)) and cough (40.36%(136/337)). Only one pediatric case with Rett syndrome developed critically severe pneumonia. A total of 194 pediatric cases had imaging examination, 64(32.99%) showed pulmonary inflammatory lesions. There were 755 adult cases infected with Omicron variant, of whom 652(86.26%) reported symptoms, and the main manifestations were fever (73.16%(477/652)) and cough (49.85%(325/652)). Among symptomatic cases, fever was more common in pediatric cases than in adult cases, while cough was more common in adult cases than in pediatric cases, and the differences were both statistically significant ( χ2=80.87 and 8.04, respectively, both P<0.01). The fever spike was higher in pediatric cases than in adult cases ((39.3±0.7) ℃ vs (38.6±0.6) ℃), and the difference was statistically significant ( t=9.85, P<0.001). The interval from the onset of symptoms to cycle threshold (Ct) value of the nucleic acid of Omicron variant≥35 was longer in pediatric cases than in adult cases ((13.0±3.1) d vs (10.9±3.6) d), and the difference had statistically significance ( t=2.97, P=0.004). Among 160 children aged 3 to 18 years, 54 (33.75%) received two-dose vaccination. Among the 904 adults, 388 (42.92%) received two-dose vaccination and 293 (32.41%) received a booster dose. In the adult cases, the risk of symptomatic infection was reduced by only 8% ( RR=0.92, 95% CI 0.86 to 0.98, P=0.014) following two-dose vaccination, and the risks of fever and cough following booster vaccination were reduced by 42%( RR=0.58, 95% CI 0.49 to 0.67, P=0.001) and 50% ( RR=0.50, 95% CI 0.34 to 0.78, P=0.001), respectively. Conclusions:Secondary attack rate and symptomatic rate of household infection are high in the context of the Omicron variant outbreak in Shanghai. Symptomatic infection is common in children and adults in household setting. Fever is the most common symptom and fever duration is short. Booster vaccination may provide certain protection against common symptoms caused by Omicron variant infection.

Seroprevalence of serum measles antibody in children with tumor after chemotherapy / 中华传染病杂志

Objective:To investigate the serum measles antibody in children with tumor and to provide the clinical evidence for measles vaccination strategy for this special population.Methods:From January 2016 to December 2018, the blood samples of children who were diagnosed with hematological malignancy or solid tumors and received chemotherapy in the Department of Hematology or Oncology Surgery of Children′s Hospital of Fudan University were collected. Enzyme-linked immunosorbent assay was used to quantitatively detect the level of measles IgG antibody, and dynamically monitor the changes of measles antibody level during chemotherapy. Kruskal-Wallis test and chi-square test were used for statistical analysis.Results:A total of 441 children with tumors were enrolled, with the positive rate of measles antibody of 79.1%(349/441), and only 43.3%(191/441) of children had the protective level of IgG antibody. There was a statistically significant difference of the antibody protection rate in children aged<eight months old, eight months old to <two years old, two years old to <six years old, and ≥six years old ( χ2=15.647, P<0.01). There was no statistically significant difference of the protection rate of serum measles antibody between children aged two to <six years and≥six years (43.8%(95/217) vs 41.1%(58/141), P>0.05). The protection rate of serum measles antibody in children with hematological malignancy and solid tumor were 45.6%(78/171) and 41.9%(113/270), respectively, and there was no statistically significant ( P>0.05). There were 16.3%(16/98) of children who were observed to lose the pre-existing protective antibody during chemotherapy. There was no statistically significant difference of the protection rate of serum among children who had finished chemotherapy <six months, six months to <one year, one year to <two years, and ≥two years ( P>0.05). Conclusions:Serum measles antibody is below the protective level in more than 50% of children with malignancy after chemotherapy. Chemotherapy can compromise the protective antibody against measles. It is recommended for this special population to re-schedule measles vaccine after individualized evaluation to acquire the immuneprotection against measles.

A case-control study on diarrheagenic E .coli infection in children / 中华传染病杂志

Objective To understand the regional epidemiology and antibiotic resistance pattern of diarrheagenic E .coli infection in children ,and to clarify the pathogenic association between diarrheagenic E .coli infection and childhood diarrhea .Methods Totally 680 diarrheal children in the outpatient setting and 680 non-diarrheal control children were enrolled prospectively .The stool samples were collected and the potential enteric pathogens were detected .Minimal inhibitory concentration (MIC) method was used to determine the antimicrobial susceptibility for diarrheagenic E .coli isolates .Results The isolation rates of diarrheagenic E .coli in diarrhea group and control group were 15 .6％ and 13 .1％ ,respecitvely ,and diarrheagenic E .coli was the most commonly detected enteric bacteria .Multivariate logistic regression analysis adjusted for age suggested no clinical association between diarrhea and infection with enteropathogenic E .coli (EPEC) (aOR=1 .2 ,95％ CI:0 .8-1 .8) ,enteroadhesive E .coli (EAEC) (aOR=1 .1 ,95％ CI:0 .7 -1 .6) and enterotoxigenic E .coli (ETEC) (aOR= 1 .8 ,95％ CI:0 .5 -6 .2) . Among 199 diarrheagenic E .coli strains ,the rates of resistance to ampicillin ,tetracycline ,trimethoprim-sulfamethoxazole ,azithromycin ,and ceftriaxone were 63 .8％ ,55 .8％ ,48 .2％ ,34 .2％ and 26 .6％ , respectively ,while the rates of resistance to ciprofloxacin , amoxicillin-clavulanate and cefoxitin were 4 .5％ ,1 .5％ and 0 .5％ ,respectively .Conclusions Diarrheagenic E .coli is the most common enteric bacteria detected in the stool samples from children with and without diarrhea in this study . The pathogenic role of infections with EPEC ,EAEC and ETEC in childhood diarrhea is not determined .EHEC and EIEC are rarely detected and further studies are needed to clarify the pathogenic association between infection with EHEC ,EIEC and childhood diarrhea .

Transforming growth factor-β1 induced cellular proliferation and collagen synthesis was mediated by reactive oxygen species in pulmonary fibroblasts / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>This study will explore whether reactive oxygen species (ROS) is involved in TGF-β1-induced JNK activation, pulmonary fibroblast proliferation and collagen type I and III synthesis.</p><p><b>METHODS</b>Pulmonary fibroblasts were randomly divided into control (0.4% serum) and TGF-β1 (5 µg/L) groups to detect whether TGF-β1 could induce pulmonary fibroblast proliferation, synthesis of collagen I and III, phosphorylated-JNK (p-JNK) and 8-OHdG (indicator of ROS); while in the part to explore whether NAC (N-acetyl-L-cysteine, antioxidants) has the inhibitory role in TGF-β1-induced pulmonary fibroblast, it did control (0.4% serum), H2O2 (0.1 mmol/L, positive control), H2O2+NAC (10 mmol/L), TGF-β1 (5 µg/L), TGF-β1+NAC groups. Pulmonary fibroblast proliferation, 8-OHdG levels, expressions of JNK and collagen I and III were used by MTT assay, immunofluorescence and western blot respectively.</p><p><b>RESULTS</b>In the experiments to detect the effect of TGF-β1 on pulmonary fibroblasts, compared with control, TGF-β1 significantly stimulated pulmonary fibroblast proliferation and increased collagen I and III protein, p-JNK and 8-OHdG levels. In the next experiments to explore whether NAC has the inhibitory role in TGF-β1-induced pulmonary fibroblasts, compared with control, pulmonary fibroblast proliferation and the levels of collagen I and II, p-JNK, 8-OHdG were all significantly increased in H2O2 and TGF-β1 groups; while these changes were markedly blocked with the treatment of NAC.</p><p><b>CONCLUSION</b>TGF-β1 induces pulmonary fibroblasts to generate ROS, which contributes to JNK activation and pulmonary fibroblast proliferation as well as collagen synthesis, while ROS inhibition suppresses this effet of TGF-β1 in pulmonary fibroblasts.</p>

Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast differentiation by regulating acetylated tubulin α in silicotic rat model / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the inhibition effect and mechanism of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP)on myofibroblast differentiation via regulating acetylated tubulin α (Ac-Tub α)in vivo and in vitro.</p><p><b>METHODS</b>Silicotic model were made by SiO2 douched and divided into 6 groups as follows: control (4w, 8w)group, silicotic model (4w, 8w)group and post-or pre-treatment by Ac-SDKP group. Pulmonary fibroblasts were divided into 5 groups: (1) control; (2) Ang II; (3) Ang II+Ac-SDKP; (4) Ang II+Valsartan; (5) Ang II+TCS histone deacetylase (HDAC)6 20b. The localization of Ac-Tub α and α-smooth muscle actin (SMA) were observed by immunohistochemical (IHC) and immunofluorescence staining. The protein levels of Ac-Tub α, α-SMA, collagen type I (col I) and HDAC6 were measured by western blot.</p><p><b>RESULTS</b>In silicotic nodules and interstitial fibrosis area, positive expression of α-SMA, a classical marker of myofibroblast, was ob-served by IHC, accompanied with absence expression of Ac-Tub α. Furthermore, Ac-SDKP post-treatment could attenuate the levels of col I, α-SMA and HDAC6 to 48.39%, 52.63% and 70.18% compared with the silicotic 8w group respectively. And in Ac-SDKP pre-treatment group, compared with the silicotic 8w group, these protein levels were decreased to 32.26%, 64.91% and 54.39% respectively (P<0.05). The up-regulation of Ac-Tub α was found in Ac-SDKP post-and pre-treatment and increased to 3.00 and 2.90 folds compared with the silicotic 8w group. Compared with control group, the levels of α-SMA, HDAC6 and col I in Ang II group were up-regulated to 1.66, 3.56 and 4.00 folds accompanied with down-regulation of Ac-Tub by 44.44% (P<0.05). Pre-treatment with Valsartan, TCS HDAC6 20b or Ac-SDKP could inhibited all this changes induced by Ang II in vitro.</p><p><b>CONCLUSION</b>Ac-SDKP can inhibit the myofibroblast differentiation and collagen deposition via sup-press HDAC6 and up-regulate the expression of Ac-Tub α in vivo and in vitro.</p>

Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast differentiation of MRC-5 human fetal lung fibroblasts inuced by Ang II / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on myofibroblast differentiation of MRC-5 human fetal lung fibroblasts induced by angiotensin (Ang) II.</p><p><b>METHODS</b>The study was divided into 2 step: (1) MRC-5 human fetal lung fibroblasts was induced for 48 h at different dose of Ang II and at different time point by 100 nmol/L Ang II. Then the expression of collagen type I and α-smooth muscle actin (α-SMA) were mesaured by western blot. (2) MRC-5 human fetal lung fibroblasts were divided into 4 group: (1) control, (2) Ang II, (3) Ang II+Ac-SDKP, (4) Ang II+8-Me-cAMP (a specific activator of Epac). The α-SMA expression was observed by immnocytochemical stain. The protein expression of collagen type I, α-SMA, serum response factor (SRF), myocardin-related transcription factor (MRTF)-A, exchange protein directly activated by cAMP (Epac) 1, 2 were measured by Westen blot.</p><p><b>RESULTS</b>Myofibroblast differentiation could be induced by Ang II from MRC-5 cells with a dose- and time-dependent manner. The up-regulation of SRF and MRTF-A were observed in MRC-5 cells induced by Ang II and accompanied with collagen I and α-SMA increased. Pre-treatment with 8-Me-cAMP or Ac-SDKP could attenuated all this changes induced by Ang II, and promoted the expression of Epac1.</p><p><b>CONCLUSION</b>Ac-SDKP can inhibit the myofibroblast differentiation of MRC-5 cells induced by Ang II via Epac1 activating.</p>

Anti-fibrotic role of AcSDKP through inhibition of P38MAPK pathway activity mediated transforming growth beta receptors in rat with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the distribution and expression of transforming growth factor beta (TGF-β) receptors I and II, p38 mitogen-activated protein kinase (p38 MAPK), and type I and type III collagen in the lungs of rats with silicosis and cultured pulmonary fibroblasts, and to investigate the relationship of the anti-fibrosis effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) with its inhibition of TGF-β receptor-mediated p38 MAPK pathway activity.</p><p><b>METHODS</b>Rats were randomly divided into control group, silicosis model group, and AcSDKP treatment group (n = 10 for each group). For the model group and AcSDKP treatment group, rats were intratracheally instilled with silica to establish a silicosis model. Cultured pulmonary fibroblasts from neonatal rats were divided into control group, TGF-β1 stimulation group, TGF-β receptor inhibition group, p38 MAPK pathway inhibition group, and AcSDKP treatment group. The protein expression of TGF-β receptors I and II, p38 MAPK, and type I and type III collagen were determined by immunohistochemistry and Western blot. The mRNA expression of TGF-β receptors I and II were determined by real-time PCR. The distribution and nuclear translocation of phospho-p38 MAPK in cultured fibroblasts were determined by laser scanner confocal microscopy.</p><p><b>RESULTS</b>In the AcSDKP treatment group, AcSDKP reduced the expression of TGF-β receptors I and II, phospho-p38 MAPK, and type I and type III collagen to 86.12%, 41.01%, 42.63%, 89.05%, and 52.71%, respectively, of those of the silicosis model group (P < 0.05). In cultured fibroblasts, AcSDKP reduced the mRNA expression of TGF-β receptors I and II to 42.26% and 54.33%, respectively, of those of the TGF-β1 stimulation group; the protein expression of TGF-β receptors I and II, phospho-p38 MAPK, and type 1 and type III collagen was reduced to 58.14%, 51.40%, 45.6%, 58.04%, and 44.74%, respectively, of those of the TGF-β1 stimulation group. The phospho-p38 MAPK translocation from plasma to the nucleus was also inhibited; the nucleus/plasma ratio of p38 MAPK and the protein expression of type I and type III collagen were reduced to 68.60%, 58.04%, and 44.74%, respectively, of those of the TGF-β stimulation group (P < 0.05).</p><p><b>CONCLUSION</b>AcSDKP can inhibit the expression of collagen through inhibition of TGF-β receptor-mediated p38 MAPK pathway activity, and is thus able to exert anti-fibrosis effect in rats with silicosis.</p>

Comparative proteomic analysis on anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in rats with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To perform a comparative proteomic analysis for identification of pulmonary proteins related to the progression of silicosis and anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP).</p><p><b>METHODS</b>Bronchial instillation of SiO₂powder (for 4 or 8 weeks) was applied in rats to establish a silicosis model. Ac-SDKP treatment was performed before (prevention group) or after (treatment group) SiO₂instillation. The control group was treated by bronchial instillation of sodium chloride solution of the same volume as SiO₂powder for 4 or 8 weeks. Proteins in lung tissue were separated by two-dimensional gel electrophoresis and stained with colloidal Coomassie brilliant blue. The gel images were scanned with the Lab Scan III system and analyzed with Imagemaster 6.0. The protein spots with significant differences between two groups (i.e., P value was less than 0.05 in One-way ANOVA) and with a change in volume over 30% were defined as differential proteins. Comparison was performed between the silicosis group and control group after 4 or 8 weeks, between the Ac-SDKP treatment group and silicosis group after 8 weeks, and between the Ac-SDKP prevention group and silicosis group after 8 weeks. The differentially expressed proteins were subjected to in-gel digestion with trypsin and MALDI-TOF-MS and Mascot search engine analysis to identify these proteins.</p><p><b>RESULTS</b>Thirty-three differential proteins were identified. In comparison with the control group (4 weeks), the silicosis group (4 weeks) had 17 up-regulated proteins and 11 down-regulated proteins. In comparison with the control group (8 weeks), the silicosis group (8 weeks) had 16 up-regulated proteins and 12 down-regulated proteins. In comparison with the silicosis group (8 weeks), the Ac-SDKP treatment group had 5 up-regulated proteins and 6 down-regulated proteins, and the Ac-SDKP prevention group had 8 up-regulated proteins and 10 down-regulated proteins.</p><p><b>CONCLUSION</b>Critical regulatory proteins related to silicotic fibrosis and anti-silicotic effect of Ac-SDKP have been identified. These proteins may play an important role in proliferation, apoptosis, inflammation, epithelial-mesenchymal transition, and signal transduction in silicosis.</p>