Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective:To understand and compare the clinical characteristics of children and adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.5 and BA.2 subtypes in Shanghai City.Methods:The clinical data of 524 children hospitalized with coronavirus disease 2019(COVID-19) at the Children′s Hospital of Fudan University during the period of BA.5 predominance from December 1, 2022 to January 20, 2023 were collected, which included age, gender, clinical symptoms and laboratory examination results. And the clinical data of household close contacts were also collected. The clinical data of children and their household contacts infected with Omicron BA.2 subtypes during the period of BA.2 predominance from April 4 to April 30, 2022 were collected and compared.The clinical characteristic of critical and non-critical cases, child and adult cases during the period of BA.5 predominance were compared.Statistical analyses were conducted using independent samples t-test, Mann-Whitney U test, chi-square test or Fisher′s exact test. Results:The age of 524 hospitalized children was five days to 16 years old. Among them, 301(57.4%) were male and 223(42.6%) were female. Additionally, there were 29 critical cases (5.5%) and 495 non-critical cases (94.5%). Critical cases had significantly higher fever peak, more shortness of breath occurrence, more pneumonia and underlying diseases compared to non-critical cases, with statistically significant differences ( t=12.06, χ2=34.90, 10.04 and 31.10, respectively, all P<0.05). Regarding laboratory examinations, critical cases exhibited significantly higher frequencies of decreased lymphocyte count, elevated levels of C-reactive protein, procalcitonin and interleukin-6, abnormal liver function and kidney function, and abnormal creatine kinase isoenzyme compared to non-critical cases, with statistically significant differences ( χ2=8.18, Z=-4.61, Z=-4.28, Z=-5.13, χ2 =195.90, Fisher′s exact test and χ2=136.13, respectively, all P<0.05). Non-critical children cases infected with Omicron variant BA.5 subtype exhibited a higher proportion of symptomatic infections compared to adults. Among children, the occurrence rates of fever and gastrointestinal symptoms (nausea, vomiting, diarrhea) were higher, whereas among adults, the occurrence rate of cough was higher. The differences were statistically significant ( χ2=11.16, 11.83, 8.50 and 28.14, respectively, all P<0.05).From December 1, 2022 to January 20, 2023, a total of 588 children cases and 791 adult cases were collected, while from April 4 to April 30, 2022, a total of 355 children cases and 755 adult cases were collected.In the children group, the occurrence rates of cough, convulsions and critical cases were higher in BA.5 subtype-infected children compared to those infected with the BA.2 subtype, with statistically significant differences ( χ2=37.95, 40.78 and 15.54, respectively, all P<0.001).In the adult group, BA.5 subtype-infected individuals had higher fever peak, longer duration of fever, and higher occurrence of fever, cough and gastrointestinal symptoms, compared to those infected with the BA.2 subtype.The differences were statistically significant ( t=-4.40, Z=-9.64, χ2=47.29, 124.09 and 29.90, respectively, all P<0.001). Conclusions:During the peak periods of BA.5 subtype of the Omicron variant in Shanghai City, critical cases have severe systemic symptoms and a higher prevalence of underlying diseases compared to non-critical cases. Among non-critical cases infected with BA.5 subtype, the proportion of symptomatic infections in children is higher than adults, with fever and gastrointestinal symptoms more common than adults, while cough symptoms are more common seen in adults.The occurrence rate of convulsions and critical cases is higher in children infected with variant BA.5 subtype compared to those infected with BA.2 subtype.The systemic symptoms are more severe in adults infected with BA.5 subtype compared to those infected with BA.2 subtype.

Objective:To understand the epidemiological and clinical characteristics, and treatment outcomes of neonatal varicella during the era of the single-dose varicella vaccine (VarV) strategy in China, and to provide relevant evidence for the prevention of neonatal varicella.Methods:The clinical data of neonatal varicella cases from 2010 to 2020 at the Children′s Hospital of Fudan University were retrospectively collected. The clinical data included epidemiological exposure, vaccination history of family members, complications, treatment, outcomes, hospital stay and hospital cost. Independent sample t test and Spearman rank correlation coefficient were used for linear correlation analysis. Results:A total of 125 neonatal varicella cases were treated. Among them, 90.4%(113/125) had a clear history of exposure to a family member with varicella or herpes zoster before onset, with 94 cases involving the mother. Of the 94 mothers, 35(37.2%) had received one dose of VarV during childhood, four siblings had also received one dose of VarV, and four grandparents and one nanny had not been vaccinated with either VarV or shingles vaccine. All neonatal varicella cases were treated with intravenous acyclovir upon admission. Neonatal varicella cases with complications had a longer hospital stay ((4.9±2.0) days) and incurred higher hospital cost ((5 739.9±3 868.2) yuan) compared to those without complications ((4.1±1.2) days and (4 047.0±1 556.0) yuan, respectively). These differences were both statistically significant ( t=2.18, 2.34, respectively; both P<0.05). All neonatal varicella cases survived. There was a positive correlation between the hospital cost and the days from disease onset to hospitalization ( r=0.183, P=0.041). The hospital cost in the group whose mothers had received one dose of VarV was lower compared to that in the group whose mother had not been vaccinated ((3 857.9±899.0) yuan vs (4 673.8±2 228.6) yuan), with the difference statistically significant ( t=2.46, P=0.016). Conclusions:To prevent neonatal varicella, it is recommended that children of appropriate age complete two doses of VarV schedule, susceptible parents of reproductive age receive two doses of VarV, and individuals aged 50 years and older receive shingles vaccine.

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.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objective:To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B.Methods:Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test.Results:A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance.Conclusion:Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log 10IU/ml), HBsAg level at 24 weeks (≤ 0.92 log 10IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log 10IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log 10IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

Objective:To understand the clinical characteristics of children with SARS-CoV-2 Omicron infection imported from Hong Kong Special Administrative Region.Methods:This retrospective study was conducted to collect the data including clinical manifestations, outcomes and vaccination of 107 children with SARS-CoV-2 Omicron infection imported from Hong Kong Special Administrative Region to be admitted to the designated referral hospital in Shanghai from February to March 2022. According to the occurrence of clinical symptoms, the cases were divided into asymptomatic group and symptomatic group. According to the age of diagnosis, the cases were divided into <3 years group, 3-<6 years group and 6-<18 years group, and the clinical manifestations in different age group were analyzed with t-test and Mann-Whitney rank-sum test. Besides, to analyze the effectiveness of vaccination against SARS-CoV-2 Omicron infection in different age group, the cases aged 3-<18 years were also subdivided into unvaccinated group, 1-dose group and 2-dose group, and the relative risk ( RR) was used to demonstrate the effectiveness. Results:Among the 107 cases, 66 were male and 41 were female, with infection age of 10 (5, 14) years. There were 29 cases in the asymptomatic group, and 78 cases in the symptomatic group, and no significant difference in the age of infection was observed between the 2 groups (11 (6, 14) vs. 10 (5, 14) years, Z=0.49, P>0.05). And there were no severe cases in symptomatic group. The length of hospitalization was (18±6) days, and was longer in symptomatic group than that in asymptomatic group ((19±6) vs. (16±7) d, t=0.17, P=0.030). Eight-two cases (76.6%) had a history of epidemiological exposure and, among whom, 81 cases (75.7%) were associated with household transmission. Among symptomatic group, 57 cases (73.1%) had fever and 20 cases (25.6%) had cough. Of the 74 cases undergoing chest CT examination, 17 cases (23.0%) showed mild abnormalities. Of the 83 cases who received the lab tests, 23 cases (27.7%) had white blood cell counts<4×10 9/L, 3 cases (3.6%) had C-reaction protein >8.0 mg/L, and 6 cases (7.2%) had slightly elevated aspartate transaminase and alanine aminotransferase. Among the 92 children aged 3-<18 years, 31 cases were unvaccinated, 34 cases received 1 dose, and 27 cases received 2 doses. The interval between the last vaccination and infection was 2.2 (0.6, 6.0) months; the interval between the last vaccination and infection in the 2-dose group was longer than that in 1-dose group (6.0 (4.5, 7.3) vs. 0.7 (0.3,2.0) months, Z=3.59, P<0.001).The risk of symptomatic infection was reduced by 45% (RR=0.55, 95% CI 0.35-0.87) with two-dose vaccination compared to non-vaccination in cases aged 3-<18 years. All these cases recovered completely. Conclusions:Children infected with SARS-CoV-2 Omicron are usually mild or asymptomatic. Household transmission is the main pattern of infection with SARS-CoV-2 Omicron in children. Two-dose SARS-CoV-2 vaccination in children aged 3-<18 years can provide partial protection against disease caused by SARS-CoV-2 Omicron.

Objective: To investigate the influence of mechanical debridement on the subgingival microbiome in chronic periodontitis by 16S rRNA high-throughput sequencing. Methods: Patients with generalized moderate to severe chronic periodontitis were recruited into this study and received oral hygiene instruction and supragingival scaling. One week later, they received ultrasonic and manual subgingival scaling and root planning. Clinical parameters were recorded and subgingival plaques were sampled at baseline and 3 months and 6 months after treatment. The comprehensive profiles of the subgingival microbiome were analyzed by sequencing the V3-4 region of 16S rRNA with the Illumina MiSeq platform. Results : Alpha diversity analysis showed that the richness and diversity of the subgingival community were consistent before and after treatment, but a significant difference in community structure was detected only between baseline and month 3 by principal coordinates analysis (PCoA). After 3 months, the clinical parameter as probing depth (PD) decreased significantly and the relative abundances of the genera related to periodontitis such as Porphyromonas, Treponema, Tannerella, and Filifactor decreased significantly. Meanwhile, the relative abundances of the genera associated with periodontal health increased, such as Capnocytophaga, Kingella. Six months later, however, less genera related to periodontitis decreased significantly from the baseline level, such as Filifactor. PD decreased significantly compared with baseline, but increased significantly compared with 3 months after treatment. Conclusion Mechanical debridement alone could relieve periodontal inflammation and balance microbial dysbiosis and the greater efficacy occurred 3 months after treatment.

【Objective】 To describe the BMI growth trajectories from birth to 24 months and examine the effects of fully breastfeeding time and breastfeeding duration on the BMI growth trajectories. 【Methods】 We conducted a follow-up study of a cohort of 1 388 eligible births. Height and weight were measured at birth, every 3 months to 12 months, and every 6 months to 24 months. Detailed demographic, feeding, activity and diseases data were also collected prospectively. Latent growth mixture modeling was conducted to model the BMI growth trajectories from birth to 24 months. Mixed-effects logistic regression analyses were made to examine the impacts of breastfeeding on this outcome. 【Results】 We identified six BMI trajectory patterns in the 1 285 infants analyzed and labeled them as follows: "normative growth" (26.6%), "normal-accelerating growth" (8.7%), "normal-decelerating growth" (11.7%), "lower-persistent growth" (6.6%), "rapid growth" (26.8%), and "rapid-accelerating growth" (19.5%). Mixed-effects logistic regression analyses revealed that fully breastfeeding ≥ 3 months could significantly decrease the risk of "rapid growth" (OR=0.71, 95% CI 0.51-0.98) and "rapid-accelerating growth" (OR=0.53, 95% CI 0.37-0.75). After adjustment for confounding factors, the relationship remained significant (OR=0.61, 95% CI 0.41-0.89; OR=0.46, 95% CI 0.31-0.68). Weaning before 6 months could significantly increase the risk of "rapid growth" (OR=1.76, 95% CI 1.19-2.61) and "rapid-accelerating growth" (OR=2.08, 95% CI 1.38-3.14). These associations persisted after adjustment for confounding factors (OR=1.69, 95% CI 1.08-2.71; OR=1.88, 95% CI 1.18-2.99). 【Conclusion】 In rural Western China, the main BMI growth trajectory patterns include "normative growth" , "rapid growth" , and "rapid-accelerating growth" . Prolonging breastfeeding may reduce excess weight gain during infancy.

Objective:To monitor the epidemiological characteristics of viral etiology in children with influenza-like illness and to guide the prevention and management of acute respiratory tract infections in childhood.Methods:Nasopharyngeal swabs were collected from the outpatient children seeking medical care in Children′s Hospital of Fudan University, Shanghai for influenza-like illness between January 2015 and December 2018. Multiplex real-time polymerase chain reaction was performed to detect respiratory syncytial virus (RSV), influenza virus (Flu), adenovirus (ADV), parainfluenza virus (PIV, type Ⅰ to type Ⅳ) and enterovirus (EV), and the epidemiological data were analyzed. Chi-square test was used for statistical analysis.Results:A total of 2 271 patients with influenza-like illness were enrolled, age range from two months to 182 months old, 1 280 cases(56.4%) were positive for the target respiratory viruses tested on respiratory samples. The detection rates of FluA, FluB, PIV, EV, ADV, RSV were 15.1%(343/2 271), 12.5%(284/2 271), 8.4%(191/2 271), 7.8%(177/2 271), 5.1%(116/2 271) and 6.7%(152/2 271), respectively.The detection rates of influenza virus were statistically different among the age groups ( χ2=39.33, P<0.05), which showed an increasing trend with the increasing ages. The detection rate of RSV was 9.7%(35/361) in infant group from zero to 12 months old, which was higher than other age groups. Usually, FluA had two epidemic peaks during the winter and summer seasons, the epidemics of FluB and RSV peaked during the winter season, and EV and PIV were more prevalent in the summer season. Conclusions:Influenza virus remains the most common viral pathogen responsible for childhood influenza-like illness in Shanghai.Influenza virus has high incidence in winter.Widely influenza vaccination is highly recommended for the effective prevention the influenza outbreaks.Continuous monitoring the epidemic trend of viral respiratory infections is imperative for the prevention and control of diseases.