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:This study evaluates the performance of chemiluminescence assay, which is designed to detect Hepatitis D Virus (HDV) Immunoglobulin G (IgG) antibodies.Methods:A comparative analysis was conducted among chemiluminescence anti-HDV IgG reagent, the magnetic particle-based domestic reagent A and domestic reagent B, and the Robo Gene HDV RNA kit, using 1909 HBsAg-positive plasma samples. This comparison aimed to delineate clinical specificity and detection accuracy. The anti-HDV IgG reagent precision was assessed at three different concentration levels following the Clinical Laboratory Standards Institute EP5-A2 guidelines. The specificity of the assay was validated using 200 HAV IgM positive, 545 HBsAg-positive but anti-HDV IgG-negative, 350 anti HCV positive plasma samples and 200 healthy human blood samples. Additionally, a concordance study was conducted with 545 HBsAg-positive and 37 anti-HDV IgG-positive plasma samples, comparing the anti-HDV IgG reagent against reagent A.Results:1 909 HBsAg-positive plasma samples were tested using 3 anti HDV IgG reagent and 1 HDV RNA reagent, 19 samples were identified as anti-HDV IgG-positive. The anti-HDV IgG demonstrated superior accuracy and specificity. The assay exhibited excellent precision, with intra-assay coefficient of variation (CV) values ranging from 1.57% to 4.30%, and inter-assay CV values between 1.71% and 4.67% for detecting samples at high, medium, and low concentration levels. Concordance with Reagent A showed consistent results in both positive and negative detections.Conclusion:In this study, the anti-HDV IgG reagent (chemiluminescence method) displayed outstanding specificity in detecting clinical samples and exhibited a high conformity rate with commercialized reagents, making it potentially suitable for screening anti-HDV IgG in HBsAg-positive samples.

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

BACKGROUND:At present,the use of a locking bone plate combined with steel wire or steel cable for the treatment of periprosthetic femoral fracture often adopts monocortical fixation,which is not stable and the proximal end of the bone cannot be achieved anatomically fitted by plate.The customized anatomical plate system can effectively solve this problem. OBJECTIVE:To explore the biomechanical strength of a customized anatomical plate system in fixation of Vancouver BI periprosthetic femoral fracture. METHODS:CT thin layer scanning data of normal femurs of 1 006 cases were selected and input into the MIMICS 21.0 software to establish the three-dimensional reconstruction model of the femur,which was set as the three-dimensional reconstruction group.56 complete human femoral specimens were selected as the femoral specimen group.The measured results of the two groups for femoral anatomical appearance were compared.If there was no significant difference between the two groups,the approximate appearance of a customized anatomical plate system was designed based on the measurement results in MIMICS 21.0 software and NX11.0 software.The customized anatomical plate system was designed and prepared according to the above measurement results.Eight pairs of frozen human femurs were selected to make Vancouver BI periprosthetic femoral fracture,which of the left were thin layer scanned by dual-source CT to obtain data.The data were transferred to determine the customized anatomical plate system model by the above design software.Eight sets of customized anatomical plate systems were ultimately produced,relying on the instrument company.The eight pairs of models were numbered 1-8.The left side was fixed with the customized anatomical plate system(customized anatomical plate system group);the right side was fixed with a metal locking plate system-large locking plate(claw plate group).L1-L4 and R1-R4 were subjected to vertical short-cycle loading test and vertical loading test.L5-L8 and R5-R8 were subjected to horizontal short-cycle loading test and four-point bending test.The vertical loading test and four-point bending test were used to collect bending load,bending displacement,and bending strain.Two short cycle loading tests were used to collect strain displacement to compare the maximum load,maximum displacement,bending stiffness,and short-period displacement resistance of the two kinds of bone plates. RESULTS AND CONCLUSION:(1)There were no significant differences in all indexes between the three-dimensional reconstruction group and the femoral specimen group(P>0.05).Individual customized anatomical plate system was designed based on the measurement results combined with digital software.(2)In the vertical loading test,the maximum load was higher(P=0.015),the maximum bending displacement was smaller(P=0.014),and the bending stiffness was higher(P=0.005)in the customized anatomical plate system group compared with the claw plate group.(3)In the four-point bending test,the maximum load was higher(P=0.023),the bending stiffness was higher(P=0.005),and the maximum bending displacement was not significant(P=0.216>0.05)in the customized anatomical plate system group compared with the claw plate group.(4)In the vertical short-cycle loading test,the average level of bending displacement in the customized anatomical plate system group(0.23±0.10 mm)was significantly lower than that in the claw plate group(0.44±0.02 mm)(P<0.05).(5)There was no significant difference in the average level of bending displacement between the two groups in the horizontal short cycle loading test(P>0.05).(6)It is concluded that the customized anatomical plate system has personalized anatomical characteristics,and the fixation of Vancouver BI periprosthetic femoral fracture is more stable,which has certain significance for clinical treatment.

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 explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames.Methods:Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ2 test. Results:NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m 2, respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) μmol/L, (346.57 ± 89.49) μmol/L, and (344.89 ±89.67) μmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) μmol/L, 73.0 (65.0, 83.5) μmol/L, and 73.0 (65.0, 83.0) μmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences ( P<0.05). Conclusion:Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

Objective To discuss the clinical diagnosis and treatment value of double-balloon enteroscopy for small intestinal bleeding diseases.Methods Retrospective collection of clinical data from 87 patients who underwent double-balloon enteroscopy for small bowel bleeding in Shantou Central Hospital from August 2019 to May 2023,and analysis of the diagnosis and treatment of small bowel bleeding causes by double-balloon enteroscopy.Results Totally 87 cases of small intestinal bleeding patients underwent a total of 117 double-balloon enteroscopy examinations,with 29 performed orally and 28 performed anally,and 30 cases simultaneously underwent both oral and anal bilateral enteroscopy examinations,with the depth of oral examination greater than that of anal examination,and the duration of oral examination shorter than that of anal examination.Among them,with a diagnostic rate of double-balloon enteroscopy at 83.91％and a pathological diagnostic accuracy rate at 83.78％.Small intestinal tumors were the main cause of small intestinal bleeding in this study,with gastrointestinal stromal tumors being the most common pathological type among small intestinal tumors.The frequency of occurrence for small intestinal tumors in individuals over 40 years old was higher than those under or equal to 40 years old group,showing statistical significance.Crohn's disease occurred more frequently in the ileum compared to jejunum,and its frequency was higher in individuals under or equal to 40 years old compared to those over 40 years old group,both differences were statistically significant(P＜0.05).A total of cases of small intestinal bleeding patients successfully underwent endoscopic hemostasis via double-balloon enteroscopy without any complications such as gastrointestinal perforation or severe bleeding during surgery.Conclusion Double balloon enteroscopy has a high diagnostic value for small intestinal bleeding and can provide basis for clinical treatment.