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 establish and validate a prediction model based on least absolute shrinkage and selection operator（LASSO）regression and classification and regression tree（CART）algorithm for acute kidney injury（AKI）in PICU.Methods:The prospective derivation cohort consisted of 350 critically ill children admitted to the PICU of Children′s Hospital of Soochow University from September 2020 to January 2021.The external data set consisting of 866 critically ill children admitted to the PICU of Children′s Hospital of Soochow University from February 2021 to February 2022 was employed for the external validation.Clinical data was obtained from the electronic medical record system，including demographic characteristics，laboratory data and the pediatric risk of mortality Ⅲ（PRISM Ⅲ）score.The variables associated with AKI were identified using LASSO regression.Subsequently，a decision tree prediction model was built using the CART algorithm.The predictive value of decision tree prediction model was evaluated using the receiver operating characteristic（ROC）curve，calibration curve，and decision curve analysis.Results:Among the 350 children in the derivation cohort，107（30.6%）developed AKI during the PICU stay；and of 866 children in the external validation cohort，165（19.1%）developed AKI during the PICU stay.The LASSO regression screened 16 candidate variables for further analysis，and the decision tree model ultimately identified 4 variables more closely associated with AKI，including fold change in serum creatinine from baseline，urine volume，PRISM Ⅲ，and C-reactive protein.The decision tree model exhibited high accuracy with AUC of 0.92，0.88，and 0.86 in the training，internal validation，and external validation cohorts，respectively.The model demonstrated good calibration and clinical applicability based on the calibration curve and decision curve analysis.Conclusion:The decision tree model based on the 4 identified clinical indicators，including fold change in serum creatinine from baseline，urine volume，PRISM Ⅲ，and C-reactive protein，is effective for the early prediction of AKI.

Objectives:This study aims to investigate the relationship between neutrophil to high-density lipoprotein cholesterol ratio(NHR)and incidence of cardiovascular disease(CVD)among individuals with metabolic associated fatty liver disease(MAFLD).Methods:We conducted a prospective cohort study utilizing health check-up data from 2006 to 2007 at Kailuan General Hospital and its 10 affiliated hospitals.The study population consisted of employees and retirees diagnosed with MAFLD,excluding those with incomplete neutrophil and high-density lipoprotein cholesterol data or a history of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.CVD was defined as the presence of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.Annual follow-ups were conducted from 2006,new-onset CVD cases identified through discharge records from the 11 Kailuan Group hospitals and records from municipal social insurance agencies,the final follow up date was December 31,2022.NHR was calculated as the ratio of neutrophil to high-density lipoprotein cholesterol,and the MAFLD cohort(n=28 952)was stratified into four groups by NHR quartiles:Q1 group(NHR<1.97,n=7 241),Q2 group(1.97≤NHR<2.57,n=7 235),Q3 group(2.57≤NHR<3.36,n=7 240),and Q4 group(NHR≥3.36,n=7 236).The Kaplan-Meier method was employed to plot survival curves for new-onset CVD,and the cumulative incidences of CVD across different NHR quartiles groups were determined.Intergroup comparisons were made using the log-rank test,and a multifactorial Cox proportional hazards regression model was used to assess the association between NHR quartiles and the risk of new-onset CVD in the MAFLD population.Results:The average follow-up duration was(14.03±3.99)years,during which 4 666 new CVD cases were recorded among the study population.The number of CVD cases across Q1 group to Q4 group were 1 061,1 167,1 186 and 1 252,respectively,with an overall incidence density of 11.5 cases per 1 000 person-years.The incidence densities for Q1 group to Q4 group were 10.4,11.4,11.7 and 12.5 cases per 1 000 person-years,respectively.The multifactorial Cox proportional hazards regression analysis revealed that higher NHR quartiles were associated with an increased relative risk of new-onset CVD(Q2 group:HR=1.13,95%CI:1.04-1.23;Q3 group:HR=1.15,95%CI:1.05-1.25;Q4 group:HR=1.22,95%CI:1.12-1.33).Conclusions:The risk of new-onset cardiovascular disease in individuals with MAFLD escalates with increasing NHR.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To evaluate the efficacy of lamb′s tripe extract and vitamin B 12 capsule (LTEVB 12C) on chronic atrophic gastritis (CAG) at different locations (antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and corpus greater curvature). Methods:From August 2011 to January 2013, 715 patients with CAG in a multicenter, randomized, double-blind, placebo-controlled trial were enrolled from 16 tertiary first-class hospitals across the country, including the First Affiliated Hospital of Air Force Medical University, Nanfang Hospital of Southern Medical University, the First Hospital of Jilin University, West China Hospital of Sichuan University, etc., there were 476 cases in the LTEVB 12C group and 239 cases in the placebo group. The patients of the LTEVB 12C group received LTEVB 12C, and the patients of placebo group received LTEVB 12C mimetic, all the medications were taken 3 capsules each time and 3 times a day after meals, and the treatment course of 2 groups were both 6 months. The efficacy evaluation criteria included the effective rate (a decrease of ≥1 in histopathological score compared with baseline after 6 months of treatment) and the reversal rate (a decrease of ≥ 2 in histopathological score compared with baseline after 6 months of treatment in the patients with moderate to severe CAG). The impact of lesion sites on the therapeutic effects of LTEVB 12C was analyzed by logistic regression analysis. The two-way unordered Cochran-Mantel-Haenszel chi-square test considering the center effect and Pearson chi-square test were used for statistical analysis. Results:The effective rates of chronic inflammation at the antrum greater curvature and corpus greater curvature (23.3%, 110/473 vs. 13.0%, 31/239; 20.3%, 96/472 vs. 12.6%, 30/239), the effective rates of atrophy at the antrum lesser curvature, antrum greater curvature, gastric angle, corpus lesser curvature, and the corpus greater curvature (27.0%, 118/437 vs. 15.7%, 34/216; 29.2%, 126/432 vs. 18.5%, 38/205; 27.8%, 121/435 vs. 16.7%, 36/216; 32.5%, 127/391 vs. 19.8%, 37/187; 33.0%, 119/361 vs. 21.8%, 39/179), and the effective rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (45.0%, 112/249 vs. 29.8%, 31/104; 53.8%, 86/160 vs. 33.9%, 21/62; 45.8%, 103/225 vs. 24.0%, 25/104; 51.9%, 83/160 vs. 28.3%, 17/60) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=10.76, 6.39, 9.69, 7.91, 11.05, 9.62, 8.57, 5.20, 7.11, 12.45, and 6.73; all P<0.05). The reversal rates of chronic inflammation at the corpus lesser curvature and corpus greater curvature (5.2%, 12/231 vs. 0, 0/123; 4.7%, 8/170 vs. 0, 0/88), the reversal rates of atrophy at the antrum lesser curvature, antrum greater curvature, corpus lesser curvature, and the corpus greater curvature (6.8%, 22/323 vs. 1.3%, 2/151; 9.2%, 29/315 vs. 1.4%, 2/144; 14.2%, 38/267 vs. 2.5%, 3/121; 20.8%, 35/168 vs. 5.8%, 4/69), and the reversal rates of intestinal metaplasia at the antrum lesser curvature, antrum greater curvature, gastric angle, and the corpus lesser curvature (29.8%, 39/131 vs. 9.1%, 4/44; 41.0%, 32/78 vs. 12.5%, 3/24; 33.3%, 44/132 vs. 4.8%, 3/63; 50.0%, 37/74 vs. 8.7%, 2/23) of the LTEVB 12C group were all higher than those of the placebo group, and the differences were statistically significant ( χ2=6.58, 5.12, 5.60, 8.61, 11.43, 6.59, 7.30, 4.95, 15.92, 7.62; all P<0.05). There were no statistically significant differences in the effective rates and reversal rates of active inflammation at different locations between the LTEVB 12C group and the placebo group (all P>0.05). The results of logistic regression analysis (taking the antrum lesser curvature as the reference) further confirmed that the reversal rates of chronic inflammation ( OR=0.22, 95% confidence interval (95% CI): 0.07 to 0.67; OR=0.24, 95% CI: 0.07 to 0.80), atrophy ( OR=0.28, 95% CI: 0.16 to 0.49; OR=0.28, 95% CI: 0.16 to 0.49), and intestinal metaplasia ( OR=0.42, 95% CI: 0.24 to 0.77; OR=0.20, 95% CI: 0.08 to 0.52) at the corpus lesser curvature and corpus greater curvature were all higher than those at the antrum lesser curvature, and the differences were statistically significant (all P<0.05). There were no statistically siginificant differences in the reversal rates of the aforementioned pathological features between the antrum greater curvature, gastric angle, and the antrum lesser curvature (all P>0.05). Conclusion:LTEVB 12C can achieve good efficacy in the treatment of CAG, and the chronic inflammation, atrophy, and intestinal metaplasia at multiple locations are improved, especially at the corpus lesser curvature and the corpus greater curvature.

Senile chronic heart failure(CHF)complicated with sarcopenia can further degrade patients'quality of life,and increase the occurrence of falls,disability and mortality.Currently,western medicine preventive and treatment for sarcopenia mainly depend on nutritional support and exercise therapy,but their efficacy remained uncertain.Traditional Chinese medicine(TCM)therapy has the advantages of holism and syndrome differentiation and treatment,and its application in senile CHF complicated with sarcopenia is worthy of further exploration.This paper sorted out the relevant statements in the Treatise on Exogenous Febrile and Miscellaneous Diseases,and concluded that the clinical manifestations of senile CHF complicated with sarcopenia are similar to those of heart water and consumptive disease in the Treatise on Exogenous Febrile and Miscellaneous Diseases.The statements in Treatise on Exogenous Febrile and Miscellaneous Diseases will guide the identification of etiology and pathogenesis as well as the diagnosis and treatment for senile CHF complicated with sarcopenia.The analysis of the pathogenesis indicated that heart water and consumptive disease were induced by deficiency of heart and spleen and kidney,five kinds of overstrain and seven types of impairment,water pathogen insulting heart,and internal stagnation of blood stasis.Therefore,it is proposed that the core pathogenesis of senile CHF complicated with sarcopenia is due to the deficiency of heart,spleen and kidney yang,and water blended with blood stasis.The classical prescriptions such as Ling Gui Zhu Gan Tang,Zhenwu Tang,Sini Tang,Shenqi Pills,Jianzhong Tang and Wuling Powder can be used by modification or combination based on syndrome differentiation in treating senile CHF complicated with sarcopenia.For both of the congenital and acquired origin(spleen and kidney)of elderly patients with CHF complicated with sarcopenia are deficient,the utilization of herbs for invigorating spleen and boosting kidney on the basis of syndrome differentiation may achieve good efficacy.

Objective To analyze the correlation between venous thromboembolism(VTE)and traditional Chinese medicine(TCM)constitution types in elderly frail patients.Methods A retrospective study was conducted on 1 428 elderly frail patients admitted to the Second Comprehensive Department of Guangdong Provincial Hospital of Chinese Medicine from January 2019 to June 2023.Patients were divided into a venous thrombsis(VT)group(n=187)and a non-VT group(n=1 241)based on VTE occurrence.Baseline data,including age distribution,Padua scores,Wells scores,and TCM constitution types,were compared between the two groups.Multivariate logistic regression analysis was performed to identify factors for influencing VTE in elderly frail patients.Results(1)Compared with the non-VT group,the VT group had significantly higher total hospitalization costs,length of stay,age,Fried scores,Padua scores,and Wells scores,with statistically significance(P＜0.001).(2)Compared with the non-VT group,the VT group had a higher proportion of high VTE-risk individuals and those with Wells scores of 2 points,with statistically significance(P＜0.001).(3)The age distribution of VTE patients showed an increasing trend in the age groups of 60-69,70-79,80-89,and ≥90-year-old,with a significant difference compared to the non-VT group(P＜0.001).(4)The VT group had a higher proportion of qi-deficiency,blood-stasis,and qi-depression constitutions than the non-VT group(P＜0.05 or P＜0.001).(5)Multivariate logistic regression analysis(after adjusting age,gender,frailty,and other scores)showed that qi-deficiency and yang-deficiency constitutions were non-susceptible,while damp-heat,blood-stasis,and qi-depression constitutions were susceptible to VTE in elderly frail patients(P＜0.05 or P＜0.01).Conclusion VTE in elderly frail patients is significantly correlated with TCM constitution types.Deviated constitutions are characteristic of TCM constitution types in elderly frail patients,and damp-heat,blood-stasis,and qi-depression constitutions are risk factors for VTE in this population.