The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective:To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality.Methods:This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results:The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups ( P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×10 9/L, 479 (298, 594) vs. 268 (124, 424) μg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) μg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases ( OR=0.01, 95% CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) ( OR=3.31, 95% CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) ( OR=1.56, 95% CI 1.05-2.32, P=0.029) and D dimer ( OR=1.49, 95% CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95% CI 0.79-0.94), 0.89 (95% CI 0.84-0.95) and 0.87 (95% CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions:Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

Objective:To comprehensively evaluate the effectiveness of preventive measures for acute kidney injury (AKI) in children and identify the effective strategies.Methods:Databases were systematically searched including CNKI, Wanfang, VIP, China Biology Medicine National Knowledge Infrastructure, PubMed, Embase, Cochrane Library databases, and the reference lists of relevant papers for randomized controlled trials on preventing pediatric AKI up to December 2023. Literature screening was conducted based on the inclusion and exclusion criteria, followed by data extraction and quality assessment of included studies. Traditional and network meta-analyses were performed, along with trial sequential analysis (TSA).Results:A total of 21 studies involving 3 483 children were included. Traditional and network meta-analysis showed that dexmedetomidine was effective in preventing AKI in children undergoing cardiac surgery or cardiac angiography ( OR=0.26, 0.27; 95% CI 0.11-0.64, 0.13-0.58). Remote ischemic preconditioning (RIPC) was effective in preventing AKI in children after cardiac surgery ( OR=0.43, 0.44; 95% CI 0.24-0.79, 0.23-0.83). Traditional and network meta-analysis specific to children with sepsis or septic shock showed that balanced solution was effective in preventing pediatric AKI ( OR=0.58, 0.52; 95% CI 0.42-0.79, 0.37-0.73). TSA indicated that the total sample sizes of dexmedetomidine (348 cases) and RIPC (666 cases) both reached the required information size (320 and 534 cases); additionally, the Z-curve for balanced solution (cumulative Z=3.38) crossed the TSA monitoring boundary ( Z=3.29). Conclusion:Dexmedetomidine reduces the risk of AKI in children undergoing cardiac surgery or cardiac angiography, RIPC decreases the risk of AKI in children after cardiac surgery, and balanced solution lowers the risk of AKI in children with sepsis or septic shock.

Objective To investigate the correlation between exposure of uric acid accumulation and the risks of acute pancreatitis(AP)in the population in Kailuan Group.Methods A prospective study was performed based on thesubjects receiving annual physical examination during 2006 to 2010 in Kailuan Group.All of them had no AP history but had complete data on UA.The starting point of follow-up was when the subjects completed the health examination in 2010,and the end point was new AP events,deaths or the end of follow-up(2021-12-31).Exposure of uric acid accumulation(cumUA)was calculated according to the average values of uric acid measured in each two consecutive physical examinations and the intervalbetween these two consecutive physical examinations.The cumulative incidences of AP indifferent subgroups(determined by the quartile of cumUA)were described using Kaplan-Meier product limit-method and compared by log-rank test.Multivariate Cox proportional hazards regression model was used to analyze the impacts of different cumUA subgroups on new occurrence of AP events.Results A total of 55,799 subjects were included in this study.The subjects were divided into four groups according to the quartile of cumUA.Sex ratio,average age,BMI,systolic blood pressure(SBP),diastolic blood pressure(DBP),FPG,TC,TG,LDL-C,HDL-C,smoking,alcohol consumption,education≥9 years,physical exercise,history of hypertension,and history of cholelithiasis differed significantly among the groups(P<0.05),there was no difference in diabetes history among the 4 groups(P=0.30).153 patients developed AP during an average follow-up of(10.52±1.75)years,the incidence rates were 1.65,2.76,2.13 and 3.96 per 10 000 person-year in the Q1,Q2,Q3and Q4,respectively(P<0.01).After adjusting sex,age,TC,TG,eGFR,smoking,alcohol consumption,education,physical activity,and history of hypertension,diabetes,or cholelithiasis,Multivariate analysis showed a significantly increased risk in Q4(HR=1.77,95%CI:1.07～2.92)as comparing with Q1.After excluding deaths during the follow-up period,Multivariate Cox regression analysis was performed again in Q4 HR=1.75(95%CI:1.04～2.95).Conclusions With the increase of cumUA exposure,both morbidity and risk of AP occur-rence have the tendency of rising.

Objective:To investigate the changes of different cytokines in systemic juvenile idiopathic arthritis（SJIA）and their role in early diagnosis.Methods:A retrospective study was conducted to select pediatric patients with fever accompanied by elevated levels of CRP，erythrocyte sedimentation rate（ESR），and ferritin who visited the Department of Renal Immunology，Children's Hospital of Soochow University from November 2019 to January 2023.Compare the differences in CRP，ESR，ferritin，and 34 plasma cytokines levels between children with SJIA and other autoimmune diseases.Cytokine risk was analyzed by regression；Correlation analysis was performed to determine whether cytokines were associated with lymphocyte subsets and disease activity.Results:During the study period，118 children with fever accompanied by elevated CRP，ESR and ferritin were eligible，among whom 20 children with SJIA were diagnosed，and 98 children with other autoimmune diseases were diagnosed.There was no statistically significant difference in CRP and ESR between SJIA patients and children with other autoimmune diseases（Z values were 0.721 and 0.345，all P>0.05）；There were significant differences in ferritin，IL-27，IL-17A，IL-31，IFN-γ，IL-18 between children with SJIA and those with other autoimmune diseases（Z values were 2.628，-2.052，-2.763，-2.135，4.067，4.419，all P<0.05）.Univariate Logistic regression analysis showed that IL-18（ OR=1.003，95% CI：1.002~1.004， P<0.001），IFN-γ（ OR=1.004，95% CI：1.001~1.007， P=0.004），IL-27（ OR=0.846，95% CI：0.716~0.999， P=0.049），IL-31（ OR=0.657，95% CI：0.451~0.959， P=0.028）were closely related to the occurrence of SJIA，and stepwise Logistic regression analysis indicated that the increase of IL-18（ OR=1.005，95% CI：1.003~1.009， P=0.004）increased the risk of SJIA，and the increase of IL-5（ OR=0.619，95% CI：0.402~0.953， P=0.029）decreased the risk.IL-18（ r=0.673， P=0.020），IL-27（ r=0.486， P=0.041）and TNF-α（ r=0.560， P=0.016）were positively correlated with the activity of SJIA. Conclusion:IL-18 presents a characteristic cytokine positively correlated with the risk of SJIA，while IL-5 presents a protective cytokine against SJIA.Both cytokines have independent predictive power for the risk.

Objective To quantitatively measure the morphological parameters of type Ⅱ accessory navicular(AN)in CT images and analyze the mechanical changes in the foot caused by painful type Ⅱ AN.Methods The CT images of 51 patients with type Ⅱ AN were analyzed retrospectively;According to whether the medial foot was painful,we divided the data into two groups,including the pain type Ⅱ AN group(case group)and the non-pain type Ⅱ AN group(control group).The measured data included the navicular and medial joint space(MeJS),middle joint space(MiJS),lateral joint space(LJS),talar-accessory navicular distance(TAND),the maximum diameter(MaD)and minimum diameter(MiD)of AN,and the difference of the relevant data using independent sample t-test was measured.Results Compared with the control group,the MeJS,MiJS,and LJS in the case group showed that the joint space of painful type Ⅱ AN was widened,and there was a significant difference(P＜0.05).Compared with the control group,the TAND,MaD,and MiD of the case group had no significant change,and there was no significant difference(P＞0.05).Conclusion In pain-ful type Ⅱ AN foot,the posterior tibial tendon(PTT)is attached to AN,which destroys the balance of force on the foot,resulting in the widening of the distance between the navicular and AN.

Autoimmune pancreatitis(AIP)is an immune-mediated,special type of chronic pancreatitis,which can involve multiple organs.The clinical manifestation of AIP is complex and varied,making the diagnosis and treatment challenging.With reference to the latest guidelines and studies from both domestic and international sources,this guideline comprises 20 recommendations regarding the diagnosis,treatment,follow-up,and prognosis of AIP.The aim of this guideline is to promote the care capability and improve the outcome of patients with AIP in China.