Development of nanobodies targeting hepatocellular carcinoma and application of nanobody-based CAR-T technology.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients' cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative. METHODS: In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation. RESULTS: Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo. CONCLUSIONS: In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

Emergence and high prevalence of unusual rotavirus G8P[8] strains in outpatients with acute gastroenteritis in Shanghai, China.

Group A rotavirus (RVA) is considered an important cause of acute gastroenteritis (AGE) in all age groups, especially in children. We investigated the epidemiology of RVA in outpatients aged ≤ 16 years at the Children's Hospital of Fudan University, Shanghai, China. In this study, 16.6% (246/1482) were infected with RVA. The detection rate of RVA was significantly higher in the year of 2021 (20.3%, 147/725) compared to the year of 2020 (14.5%, 77/531) and 2022 (9.7%, 22/226) (p = 0.000). RVA infection was prevalent in all seasons from 2020 to 2022, with a different monthly distribution observed in different years. Among 246 RVA-positive samples, 14 different RVA genotypes were detected with different frequencies. Overall, G9P[8] (45.5%, 112/246) was the most common RVA genotype, followed by G8P[8] (37.4%, 92/246) and G3P[8] (4.1%, 10/246). The prevalence of G/P combinations varied from 2020 to 2022. G9P[8] was the most prevalent circulating genotype in 2020 (68.2%, 15/22) and 2021 (57.8%, 85/147). However, G8P[8] (68.8%, 53/77) suddenly became the most prevalent genotype in 2022 after being first identified in 2020 and prevalent in 2021. The G8 strains detected in the study were all clustered to DS-1-like G8 strains with the closest genetic distance to strains circulating in Southeast Asia. Our study demonstrated the diversity of circulating RVA genotypes in Shanghai. The sudden emergence and high prevalence of unusual G8P[8] strains deserve more concern and indicate the need for continuous surveillance of RVA in children with AGE in the future to refine future vaccine strategy.

Distinct clinical features of transplanted children with Parvovirus B19 infection.

BACKGROUND: The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven't been comprehensively described. METHODS: We searched the medical records of all the transplant recipients who attended the Children's Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children. RESULTS: A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system. CONCLUSIONS: Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern.

Adverse outcomes in subsequent pregnancies in women with history of recurrent spontaneous abortion: A meta-analysis.

OBJECTIVE: This study aimed to investigate the association between a history of recurrent spontaneous abortion (RSA) and adverse outcomes in women with spontaneous conception. METHODS: A search strategy from the inception to March 3, 2023 was run in PubMed, Embase, Cochrane Library, and Web of Science databases. The odds ratio (OR), and the 95% confidence interval (CI) or point estimation were used as the evaluation indexes. Each outcome measure tested was assessed for heterogeneity using the Cochran Q test. Sensitivity analyses were performed to test the credibility of the meta-analysis results. RESULTS: Fifteen studies involving 1 475 389 pregnant women were included. A history of RSA was associated with gestational diabetes (OR: 2.21, 95% CI: 1.70-2.87, p < 0.001), preeclampsia (OR: 2.06, 95% CI: 1.49-2.86, p < 0.001), placenta previa (OR: 1.82, 95% CI: 1.09-3.02, p = 0.021), placental abruption (OR: 1.67, 95% CI: 1.36-2.06, p < 0.001), miscarriage (OR: 6.37, 95% CI: 3.83-10.57, p < 0.001), preterm birth (OR: 1.80, 95% CI: 1.36-2.37, p < 0.001), cesarean section (OR: 1.47, 95% CI: (1.13-1.91, p = 0.004), perinatal death (OR: 2.24, 95% CI: 1.39-3.60, p = 0.001), and neonatal intensive care unit admission (OR: 1.39, 95% CI: 1.01-1.92, p = 0.047). However, the associations of a history of RSA with gestational hypertension, small for gestational age, fetal anomalies, fetal growth restriction, and postpartum hemorrhage were not observed. CONCLUSION: This meta-analysis indicates a history of RSA was associated with increased risks of several adverse outcomes in pregnant women with spontaneous conception.

Pan-Genomic Analysis Identifies the Chinese Strain as a New Subspecies of Xanthomonas fragariae.

Xanthomonas fragariae is classified as a quarantine pathogen by the European and Mediterranean Plant Protection Organization. It commonly induces typical angular leaf spot (ALS) symptoms in strawberry leaves. X. fragariae strains from China (YL19, SHAQP01, and YLX21) exhibit ALS symptoms in leaves and more severe symptoms of dry cavity rot in strawberry crowns. Conversely, strains from other countries do not cause severe dry cavity rot symptoms in strawberries. After employing multilocus sequence analysis (MLSA), average nucleotide identity (ANI), and amino acid identity (AAI), we determined that Chinese strains of X. fragariae are genetically distinct from other strains and can be considered a new subspecies. Subsequent analysis of 63 X. fragariae genomes published at NCBI using IPGA and EDGAR3.0 revealed the pan-genomic profile, with 1,680 shared genes present in all 63 strains, including 71 virulence-related genes. Additionally, we identified 123 genes exclusive to all the Chinese strains, encompassing 12 virulence-related genes. The qRT-PCR analysis demonstrated that the expression of XopD, XopG1, CE8, GT2, and GH121 out of 12 virulence-related genes of Chinese strains (YL19) exhibited a constant increase in the early stages (6, 24, 54, and 96 hours postinoculation [hpi]) of strawberry leaf infected by YL19. So, the presence of XopD, XopG1, CE8, GT2, and GH121 in Chinese strains may play important roles in the early infection process of Chinese strains. These findings offer novel insights into comprehending the population structure and variation in the pathogenic capacity of X. fragariae.

Emergence of GII.4 Sydney[P16]-like Norovirus-Associated Gastroenteritis, China, 2020-2022.

Newly evolved GII.4 Sydney[P16] norovirus with multiple residue mutations, already circulating in parts of China, became predominant and caused an abrupt increase in diagnosed norovirus cases among children with gastroenteritis in Shanghai during 2021-2022. Findings highlight the need for continuous long-term monitoring for GII.4 Sydney[P16] and emergent GII.4 norovirus variants.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. STUDY DESIGN: We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. RESULTS: A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to ≤4 years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to ≤2 years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. CONCLUSIONS: A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Surveillance and epidemiological characterization of human adenovirus infections among outpatient children with acute gastroenteritis during the COVID-19 epidemic in Shanghai, China.

BACKGROUND: Human adenovirus (HAdV) has been recognized as one of the common enteric viruses associated with acute gastroenteritis (AGE) in children. The aim of this study was carried out to illustrate the epidemiological characterization of HAdV Infections among children younger than 15 years in Shanghai during COVID-19. METHODS: During May 2020 and April 2022, 1048 fecal samples were collected from children ≤ 15 years diagnosed with AGE in the Children's Hospital of Fudan University. HAdV was identified by PCR and sequenced with specific primers. All the obtained sequences were analyzed by MEGA (version 6.0). Demographic information and clinical features data were also collected and analyzed. RESULTS: In total, 97 (9.3%, 97/1048) samples were detected to be HAdV during May 2020 and April 2022. We found an atypical upsurge in HAdV infection in the year 2021 after a major suppression in the year 2020. Approximately 84.5% (82/97) of HAdV-infected children were aged 0-60 months. Among the 97 HAdV-positive samples, only two species and five genotypes were detected. HAdV-F (88.7%, 86/97) was the most prevalent species and HAdV-F41 (87.6%, 85/97) was the most common genotype. Diarrhea, vomiting, and fever were the main clinical manifestations in children infected with HAdV. The children aged from 0 to 12 months showed simpler patterns of clinical presentation than those of children older than 13 months. CONCLUSIONS: Our findings described the epidemiological changes of HAdV infection in children with AGE during the COVID-19, which further underscored the importance of continuous surveillance of HAdV at both local and global scales.

Discrepancy between two invasive blood pressure measurements in patients receiving intra-aortic balloon pump therapy.

BACKGROUND: Hemodynamic monitoring is imperative for patients with cardiogenic shock undergoing Intra-aortic Balloon Pump (IABP) therapy. Blood pressure monitoring encompasses non-invasive, invasive peripheral arterial pressure (IPAP), and invasive central aortic pressure (ICAP) methods. However, marked disparities exist between IPAP and ICAP. This study examined the discrepancies between IPAP and ICAP and their clinical significance. METHODS: A retrospective analysis was conducted on cardiogenic shock patients who underwent IABP therapy and were admitted to the Coronary Care Unit (CCU) of a tertiary hospital in China from March 2017 to November 2022. The Bland-Altman plot illustrated the discrepancy between IPAP and ICAP. A clinically significant difference between ICAP and IPAP measurements was defined as ≥ 10 mmHg, which could necessitate alterations in blood pressure management according to current guidelines that recommend maintaining a mean arterial pressure (MAP) ≥ 70 mmHg. RESULTS: In total, 162 patients were included in the final analysis. In patients without vasopressors, the difference between ICAP and IPAP was 5.73 mmHg (95% limits of agreement [LOA], -16.98 to 28.44), whereas, in patients with vasopressors, it was 4.36 mmHg (95% LOA, -17.31 to 26.03). ICAP measurements exceeded IPAP in patients undergoing IABP therapy. However, the difference was not statistically significant between the two groups. Multivariate logistic regression revealed that higher serum lactate levels (Odds ratio [OR], 1.14; 95% confidence interval [CI], 1.03-1.27; p = 0.013) and age ≥ 60 years (OR, 13.20; 95% CI, 1.50-115.51; p = 0.020) were associated with an increased likelihood of a clinically significant MAP discrepancy. Conversely, a history of coronary heart disease was associated with a decreased likelihood (OR, 0.34; 95% CI, 0.13-0.90; p = 0.031). CONCLUSIONS: Notable discrepancies between ICAP and IPAP measurements exist in cardiogenic shock patients undergoing IABP therapy. ICAP exceeds IPAP, and factors such as age ≥ 60 years, elevated lactic acid levels, and absence of coronary heart disease contribute to this discrepancy. Enhanced vigilance is warranted for these patients, and the consideration of peripheral invasive monitoring in conjunction with IABP therapy is advised.

Flagella-Driven Motility Is Critical to the Virulence of Xanthomonas fragariae in Strawberry.

Xanthomonas fragariae (X. fragariae) is the causal agent of angular leaf spots (ALS) in strawberry plants. Recently, a study in China isolated X. fragariae strain YL19, which was observed to cause both typical ALS symptoms and dry cavity rot in strawberry crown tissue; this was the first X. fragariae strain to have both these effects in strawberry. In this study, from 2020 to 2022, we isolated 39 X. fragariae strains from diseased strawberries in different production areas in China. Multilocus sequence typing (MLST) and phylogenetic analysis showed that X. fragariae strain YLX21 was genetically different from YL19 and other strains. Tests indicated that YLX21 and YL19 had different pathogenicities toward strawberry leaves and stem crowns. YLX21 did not cause ALS symptoms, rarely caused dry cavity rot in strawberry crown after wound inoculation, and never caused dry cavity rot after spray inoculation, but it did cause severe ALS symptoms after spray inoculation. However, YL19 caused more severe symptoms in strawberry crowns under both conditions. Moreover, YL19 had a single polar flagellum, while YLX21 had no flagellum. Motility and chemotaxis assays showed that YLX21 had weaker motility than YL19, which may explain why YLX21 tended to multiply in situ within the strawberry leaf rather than migrate to other tissues, causing more severe ALS symptoms and mild crown rot symptoms. Taken together, the new strain YLX21 helped us reveal critical factors underlying the pathogenicity of X. fragariae and the mechanism by which dry cavity rot in strawberry crowns forms.

Systemic Colonization of Xanthomonas fragariae Strain YL19 Causing Dry Cavity Rot of Strawberry Crown Tissue in China.

Xanthomonas fragariae usually causes angular leaf spot (ALS) of strawberry, a serious bacterial disease in many strawberry-producing regions worldwide. Recently, a new strain of X. fragariae (YL19) was isolated from strawberry in China and has been shown to cause dry cavity rot in strawberry crown. In this study, we constructed a green fluorescent protein (GFP)-labeled Xf YL19 (YL19-GFP) to visualize the infection process and pathogen colonization in strawberries. Foliar inoculation of YL19-GFP resulted in the pathogen migrating from the leaves to the crown, whereas dip inoculation of wounded crowns or roots resulted in the migration of bacteria from the crowns or roots to the leaves. These two invasion types both resulted in the systematic spread of YL19-GFP, but inoculation of a wounded crown was more harmful to the strawberry plant than foliar inoculation. Results increased our understanding of the systemic invasion of X. fragariae, and the resultant crown cavity caused by Xf YL19.

[Cost-effectiveness analysis of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in treatment of chronic rhinosinusitis].

This study aims to evaluate the effectiveness and economic efficiency of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of chronic rhinosinusitis(CRS). The randomized controlled trial(RCT) of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS was searched against EMbase, PubMed, Cochrane Library, CNKI, VIP, SinoMed, and Wanfang. The efficacy, nasal mucociliary transport time, and safety of the therapy above in the treatment of CRS were analyzed with single-group rate and Meta-analysis, and the economy and sensitivity were evaluated from the perspective of payer. A total of 9 RCTs were included, including 1 145 patients. Meta-analysis showed that compared with Triamcinolone Acetonide Nasal Spray alone, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS patients increased the effective rate(RR=1.17, 95%CI[1.11, 1.24], P<0.000 01) and shortened the nasal mucociliary transport time(MD=-3.32, 95%CI[-5.86,-0.78], P=0.01), there was no significant difference in the incidence of adverse reactions between the two groups. The incremental cost-effectiveness analysis showed that the treatment costs of the control group and the observation group were 44.15 yuan and 1 044.96 yuan, respectively. In the Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray treatment group, 75.48 yuan was spent to improve the effective rate of CRS by 1%. The one-way sensitivity analysis indicated the days of treatment, the RR of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray, the price of unit preparation of Biyuan Tongqiao Granules, and the effective rate of Triamcinolone Acetonide Nasal Spray alone had great influence on the incremental cost-effectiveness ratio. In conclusion, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray improves the therapeutic effect on CRS. The probabilistic sensitivity analysis showed that when the willingness to pay was greater than 7 920 yuan(less than 0.1 of GDP per capita 8 098 yuan), the combined therapy was economically superior to the control. Due to the limited number of articles published, it is necessary to carry out a real-world clinical trial of Biyuan Tongqiao Gra-nules and Triamcinolone Acetonide Nasal Spray in the treatment of CRS, so as to compare the cost-effectiveness of Biyuan Tongqiao Granules and Triamcinolone Acetonide Nasal Spray.

The changing pattern of common respiratory and enteric viruses among outpatient children in Shanghai, China: Two years of the COVID-19 pandemic.

Nonpharmaceutical interventions (NPIs) taken to combat the coronavirus disease 2019 (COVID-19) pandemic have not only decreased the spread of severe acute respiratory syndrome coronavirus 2 but also have had an impact on the prevalence of other common viruses. This study aimed to investigate the long-term impact of NPIs on common respiratory and enteric viruses among children in Shanghai, China, as NPIs were relaxed after June 2020. The laboratory results and clinical data of outpatient children with acute respiratory tract infections (ARTI) and acute gastroenteritis (AGE) were analyzed and compared between the post-COVID-19 period (from June 2020 to January 2022) and pre-COVID-19 period (from June 2018 to January 2020). A total of 107 453 patients were enrolled from June 2018 to January 2022, including 43 190 patients with ARTI and 64 263 patients with AGE. The positive rates of most viruses decreased during the post-COVID-19 period, with the greatest decrease for influenza A (-0.94%), followed by adenoviruses (AdV) (-61.54%), rotaviruses (-48.17%), and influenza B (-40%). However, the positive rates of respiratory syncytial virus (RSV) and enteric AdV increased during the post-COVID-19 period as the NPIs were relaxed. Besides this, in the summer of 2021, an unexpected out-of-season resurgence of RSV activity was observed, and the resurgence was more prominent among children older than 5 years. The effectiveness of the current relaxed NPIs in control of common respiratory and enteric viruses was variable. Relaxation of NPIs might lead to the resurgence of common viruses.

Development of a multiplex droplet digital PCR assay for detection of enterovirus, parechovirus, herpes simplex virus 1 and 2 simultaneously for diagnosis of viral CNS infections.

BACKGROUND: Enterovirus (EV), parechovirus (HPeV), herpes simplex virus 1 and 2 (HSV1/2) are common viruses leading to viral central nervous system (CNS) infections which are increasingly predominant but exhibit deficiency in definite pathogen diagnosis with gold-standard quantitative PCR method. Previous studies have shown that droplet digital PCR (ddPCR) has great potential in pathogen detection and quantification, especially in low concentration samples. METHODS: Targeting four common viruses of EV, HPeV, HSV1, and HSV2 in cerebrospinal fluid (CSF), we developed a multiplex ddPCR assay using probe ratio-based multiplexing strategy, analyzed the performance, and evaluated it in 97 CSF samples collected from patients with suspected viral CNS infections on a two-channel ddPCR detection system. RESULTS: The four viruses were clearly distinguished by their corresponding fluorescence amplitude. The limits of detection for EV, HPeV, HSV1, and HSV2 were 5, 10, 5, and 10 copies per reaction, respectively. The dynamic range was at least four orders of magnitude spanning from 2000 to 2 copies per reaction. The results of 97 tested clinical CSF specimens were identical to those deduced from qPCR/qRT-PCR assays using commercial kits. CONCLUSION: The multiplex ddPCR assay was demonstrated to be an accurate and robust method which could detect EV, HPeV, HSV1, and HSV2 simultaneously. It provides a useful tool for clinical diagnosis and disease monitoring of viral CNS infections.

Prevalence and genotypes distribution of group A rotavirus among outpatient children under 5 years with acute diarrhea in Shanghai, China, 2012-2018.

BACKGROUND: Group A rotavirus (RVA) remains the main causative agent of acute diarrhea among children under five years in countries that have not yet introduced the RVA vaccine worldwide. Long-term and continuous monitoring data on RVA infection in outpatient children were lacking in Shanghai. We investigated the prevalence and distribution of RVA genotypes in outpatient children with acute diarrhea in Shanghai from 2012 to 2018. METHODS: Stool specimens of outpatient children under five years were collected from the Children's Hospital of Fudan University in Shanghai, China. All the samples enrolled in this study were detected and characterized for the P and G genotypes of RVA were determined using the semi-multiplex RT-PCR technique. RESULTS: Of 1814 children enrolled with acute diarrhea and having specimens collected, 246 (13.6%) were infected with RVA. The highest frequency of RVA was observed in children younger than two years old (87.0%, 214/246). Year-round RVA transmission was observed and the RVA detection rate peaked every winter and troughed in summer. In this study, 12 different RVA strains were identified in children. G9P[8] (49.2%, 121/246) was detected as the most prevalent genotype, followed by G-P[8] (22.8%, 56/246), G3P[8] (11.4%, 28/246), and G9P- (4.9%, 12/246). Although RVA strains detected in this study varied with the time, G9P[8] has been the most predominant circulating genotype since 2012. Furthermore, 12.2% (30/246) RVA positive samples were co-infected with other diarrhea viruses. CONCLUSION: The present analysis showed that RVA was still a major cause of children with acute diarrhea in Shanghai from 2012 to 2018. A great diversity of RVA strains circulated in children with acute diarrhea with G9P[8] being the predominant genotype since 2012. Long-term and continuous monitoring of RVA genotypes is therefore indispensable to refine future vaccine strategy in Shanghai.

Human rhinoviruses prevailed among children in the setting of wearing face masks in Shanghai, 2020.

BACKGROUND: Human rhinovirus (HRV) is the predominant etiological agent of the common cold in children and adults. A recent study showed that the inhibitory effect of face masks on viral shedding of HRV was less prominent than that on other respiratory viruses. Considering that most Chinese people have worn face masks in public area since the outbreak of coronavirus disease 2019, we aimed to find out whether HRV prevailed among children in 2020 and demonstrate the details of the epidemiological features of HRV under such a special circumstance. METHODS: We summarized the incidences of various respiratory virus infections in patients who visited the Children's Hospital of Fudan University during 2018-2020, and genotyped HRV positive nasopharyngeal specimens collected from 316 inpatients and 72 outpatients that visited the hospital in 2020. RESULTS: There was a major prevalence of HRV among children in the latter half of 2020, with a clear seasonality that HRV-As prevailed in summer while HRV-Cs in autumn. HRV-As were more prone to cause severe lower respiratory tract infections (LRTI), while HRV-Cs were closely associated with childhood wheezing. The predominant genotypes were A11, A28, A47, A82, A101, C40 and C43. Notably, A21, A82 and A101 took up larger proportions in severe cases than in non-severe cases. CONCLUSIONS: Our findings described a major prevalence of HRVs among children in 2020, which highlight the unique transmitting pattern of HRV and help to narrow the targets for antiviral strategies.

Qualitative and quantitative study of fetal posterior fossa during the first trimester in a Chinese population.

BACKGROUND: To establish the normal reference ranges for parameters related to the fetal posterior fossa in the first trimester (11 ~ 13+6 weeks of gestation) and to analyze the relationship between them and crown-rump length (CRL) among the Chinese population. METHODS: Singleton pregnancies of 11 ~ 13+6 weeks (CRL:45 ~ 84 mm) with both parents from China were randomly selected from January 2021 to November 2021. The related parameters of the posterior fossa including cisterna magna (CM), intracranial translucency (IT), brain stem (BS), brain stem to the occipital bone (BSOB), and brain stem/brain stem to occipital bone (BS/BSOB) were evaluated and measured in nuchal translucency (NT) mid-sagittal section clearly by an experienced sonographer (operator 1). To assess the reproducibility of the measurements, we randomly selected 50 pregnant women. According to the blind method, operators 1 and 2 respectively screened and measured relevant parameters. In addition, operator 1 examined and measured relevant parameters again 2 h after the first. RESULTS: This study included 1663 fetuses. All fetuses can clearly show the three spaces of the fetal posterior fossa. The ICCs (95% CI) of intra-operator reproducibility of CM, IT, BS, BSOB, BS/BSOB were 0.981 (0.952 ~ 0.991, P < 0.001), 0.929 (0.866 ~ 0.961, P < 0.001), 0.970 (0.946 ~ 0.983, P < 0.001), 0.991 (0.974 ~ 0.996, P < 0.001), 0.939 (0.892 ~ 0.965, P < 0.001), respectively; The ICCs (95% CI) of inter-operator reproducibility 0.926 (0.860 ~ 0.960, P < 0.001), 0.810 (-0.083 ~ 0.940, P < 0.001), 0.820 (0.645 ~ 0.904, P < 0.001), 0.804 (0.656 ~ 0.888, P < 0.001), 0.772 (0.599 ~ 0.871, P < 0.001), respectively. There was a linear correlation between CRL and the parameters related to the posterior fossa (CM, IT, BS, BSOB, BS/BSOB). CM (mm) = -1.698 + 0.532 × CRL (cm) (r = 0.829, P < 0.001); IT (mm) = 0.701 + 0.179 × CRL (cm) (r = 0.548, P < 0.001); BS (mm) = 0.403 + 0.349 × CRL (cm) (r = 0.716, P < 0.001); BSOB (mm) = -0.277 + 0.719 × CRL (cm) (r = 0.829, P < 0.001); BS/BSOB = 0.747-0.021 × CRL (cm) (r = 0.196, P < 0.001). CONCLUSIONS: Qualitative and quantitative assessment of the fetal posterior fossa structure was feasible in the first trimester. We constructed the normal reference ranges of CM, IT, BS, BSOB, and BS/BSOB. Furthermore, CM, IT, BS, and BSOB were positively correlated with CRL, but BS/BSOB was negatively correlated with CRL.

Full recovery after prolonged resuscitation in a pediatric patient due to fulminant myocarditis: a case report with three-year follow-up.

BACKGROUND: Fulminant myocarditis (FM) is a common life-threatening disease in pediatric patients, which can result in sudden cardiac arrest (CA). Whether prolonged cardiopulmonary resuscitation (CPR) is beneficial to FM induced CA is unknown. CASE PRESENTATION: We reported the case of an 8-year-old child with FM. At 14:49 of the day after admission, the ECG monitoring indicated ventricular flutter. The patient was immediately given continuous external cardiac compression. Electric cardioversion (energy 30J) and electric defibrillation (energy 50 J, 100 J, 100 J) were given. Continuous chest compression was conducted until extracorporeal membrane oxygenation (ECMO) successfully placed at 19:30 P.M. The total duration of CPR was 291 min. Nine days later, the ECMO was removed; and 29 days later, the patient was discharged from hospital. In the three years of follow-up, the boy showed a full recovery without neurological sequela. At present, his daily activities have returned to normal and his academic performance at school is excellent. CONCLUSIONS: Prolonged CPR can be used in FM induced in-hospital CA in pediatric patients, especially during preparation for ECMO after the failure of standard resuscitation measures.

Clinicopathological characteristics of placental chorioangioma: A clinicopathological study of 77 cases.

OBJECTIVE: To explore clinicopathological characteristics, diagnosis, differential diagnoses, treatment, and prognoses of placental chorioangioma (PCA). METHODS: Placenta of 77 cases of PCA firmly diagnosed by pathology from 2009 through 2019 were collected, and clinicopathological characteristics of the patients were retrospectively analyzed. RESULTS: Seventy-seven patients were 20-41 (mean age, 28.8) years old at onset. Thirty patients showed pregnancy comorbidity. In one patient with the largest tumor (diameter, 16 cm), intrauterine fetal demise occurred at 33 weeks of gestation. Tumors were macroscopically manifested. The placental fetal surface showed a raised dark red to a pale pink nodule, quasi-round, with a maximum diameter of 0.2-16 cm. Microscopically, the tumors had a lot of capillaries and some interstitial loose connective tissue. One case was of atypical cellular chorioangioma. Immunophenotypically, CD34 (+) and Ki-67 proliferation indexes were less than 10%. CONCLUSIONS: Large PCA often accompanies pregnancy comorbidity. Atypical cellular chorangioma is rare and may be misdiagnosed as a malignant tumor. Therefore, improvement of understanding of such tumors can provide a basis for clinical diagnosis and intervention.

Impact of COVID-19 pandemic on the prevalence of respiratory viruses in children with lower respiratory tract infections in China.

BACKGROUND: The multifaceted non-pharmaceutical interventions (NPIs) taken during the COVID-19 pandemic not only decrease the spreading of the SARS-CoV-2, but have impact on the prevalence of other viruses. This study aimed to explore the prevalence of common respiratory viruses among hospitalized children with lower respiratory tract infections (LRTI) in China during the COVID-19 pandemic. METHODS: Respiratory specimens were obtained from children with LRTI at Children's Hospital of Fudan University for detection of respiratory syncytial virus (RSV), adenovirus (ADV), parainfluenza virus (PIV) 1 to 3, influenza virus A (FluA), influenza virus B (FluB), human metapneumovirus (MPV) and rhinovirus (RV). The data were analyzed and compared between the year of 2020 (COVID-19 pandemic) and 2019 (before COVID-19 pandemic). RESULTS: A total of 7107 patients were enrolled, including 4600 patients in 2019 and 2507 patients in 2020. Compared with 2019, we observed an unprecedented reduction of RSV, ADV, FluA, FluB, and MPV infections in 2020, despite of reopening of schools in June, 2020. However, the RV infection was significantly increased in 2020 and a sharp increase was observed especially after reopening of schools. Besides, the PIV infection showed resurgent characteristic after September of 2020. The mixed infections were significantly less frequent in 2020 compared with the year of 2019. CONCLUSIONS: The NPIs during the COVID-19 pandemic have great impact on the prevalence of common respiratory viruses in China. Meanwhile, we do need to be cautious of a possible resurgence of some respiratory viruses as the COVID-19 restrictions are relaxed.