Objective: To assess the effect of 12-year-old children s pit and fissure sealants on the health of first permanent molars, so as to provide evidence for optimizing caries prevention strategies among children. Methods: In March 2025, a cluster random sampling method was used to conduct oral examinations on 965 students aged 12 from Chengdu s 2021 Comprehensive Intervention Program for Pediatric Oral Diseases. Data from the Comprehensive Intervention System for Children s Oral Diseases were referenced. Participants were divided into a sealed group ( n =755) and an unsealed group ( n =210) based on whether they had received sealants on their first permanent molars. Chi square test or analysis of variance were used to compare indicators such as caries incidence, new caries detection rate, and new caries mean (DMFT increment) between the two groups Results: The sealed group showed significantly lower caries incidence, new caries detection rate, and new caries mean (33.38%, 17.65%, 0.59±1.00) compared to the unsealed group (43.81%, 24.70%, 0.87±1.22)( χ 2/F =7.79, 18.26, 9.55, all P <0.05). However, no significant difference was found in the filled teeth ratio between the two groups (20.38% , 20.16%; χ 2=0.01, P =0.94). In girls, the sealed group exhibited significantly lower caries incidence, new caries detection rate, and new caries mean (36.78%, 20.99%, 0.69± 1.10 ) than the unsealed group (57.55%, 33.52%, 1.15±1.29) ( χ 2/F =14.42, 23.76, 10.92, all P <0.05), whereas no significant differences were observed between boys in the sealed (30.47%, 14.85%, 0.50±0.89) and unsealed groups (29.81%, 16.18%, 0.59± 1.08) ( χ 2/F =0.02, 0.41, 0.74, all P >0.05). Boys had significantly lower new caries detection rates and new caries means than girls in both groups ( χ 2/F =16.20, 6.94; 29.93, 11.84, all P <0.05). In urban areas, the sealed group had lower new caries detection rates and new caries means (19.37%, 0.68±1.04) than the unsealed group (24.66%, 0.90±1.20) ( χ 2/F =6.86, 3.94, both P <0.05). In suburban areas, all indicators for the sealed group (24.71%, 13.77%, 0.42±0.87) were significantly lower than those for the unsealed group (38.81%, 24.77%, 0.82±1.28) ( χ 2/F =5.28, 15.36, 6.00, all P <0.05). Indicators from specialized dental institutions (11.25%, 4.81%, 0.16±0.56) were significantly lower than those from county level or above general hospitals (33.33%, 19.11%, 0.38±1.00) and primary healthcare institutions (37.59%, 19.24%, 0.67±1.05) ( χ 2/F =20.99, 34.31, 21.08 , all P <0.01). Conclusions The 12-year-old children s pit and fissure sealants effectively reduce the caries incidence in first permanent molars, particularly showing significant effectiveness in girls and suburban children. Intervention strategies should be optimized according to gender.

Objective: To validate the performance of the Procleix UltrioPlex E assay (Grifols, Spain) on the Procleix Panther automated nucleic acid detection platform, which employs the TMA method to simultaneously detect HIV-1/HIV-2/HCV/HBV/HEV viruses, and to evaluate its value for screening transfusion-associated infectious diseases. Methods: In accordance with the requirements of ISO15189"Application of the Guidelines for the Accreditation of Quality and Capabilities of Medical Laboratories in the Field of Molecular Diagnostics (CNAS-CL02-A009: 2018)", "Guidelines for Performance Validation of Molecular Diagnostic Testing Procedures (CNAS-GL039: 2019)", and the "Technical Operating Procedures for Blood Banks (2019 Edition)", this study validated the reagent's performance in terms of analytical sensitivity validation, performance consistency validation, interference resistance, and cross-contamination resistance. Results: Probit analysis revealed that the 95% detection limits (95% confidence interval) for HBV, HCV, HIV, and HEV were 2.0 IU/mL, 1.5 IU/mL, 18.0 IU/mL and 3.7 IU/mL, respectively, which were consistent with the minimum detection limits stated in the kit's package insert and were comparable to the Procleix Ultrio Elite kit. Both kits were used to test the performance validation serum plate simultaneously, yielding results consistent with the serum plate (Kappa=1), indicating stable performance. Detection of medium-and low-concentration lipemia and weakly positive hemolysis samples demonstrated good interference resistance. Cross-contamination performance validation showed that the kit exhibited excellent cross-contamination resistance. Conclusion: The Procleix UltrioPlex E nucleic acid detection kit enables combined detection of HIV-1, HIV-2, HCV, HBV, and HEV, allowing single-test screening for multiple viruses in donor blood. The kit's analytical performance is stable and meets basic laboratory requirements, making it suitable for screening transfusion-associated infectious diseases in blood banks.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE To evaluate the quality of Mongolian medicine Sendeng-4 based on qualitative and quantitative analysis combined with chemical pattern recognition， in order to provide the reference for its quality control. METHODS The chemical components in Sendeng-4 were analyzed qualitatively by HPLC-Q-Exactive-MS. The contents of 16 components （methyl gallate， ethyl gallate， epicatechin， dihydromyricetin， genipin-1-O-β-D-gentiobioside， caffeic acid， catechin， corilagin， deacetylasperulosidic acid methyl ester， rutin， geniposide， luteolin， myricetin， quercetin， ferulic acid， and toosendanin） in 15 batches of Sendeng-4 （sample S1-S15） were quantitatively analyzed by HPLC-MS/MS. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares discriminant analysis were conducted and variable importance projection （VIP） value greater than 1 was used as the index to screen the differential components. RESULTS A total of 73 chemical components were identified in Sendeng-4， including 20 flavonoids， 16 tannins， 14 organic acids， etc. According to the quantitative analysis， the results exhibited that the average contentsthe of above 16 components in 15 batches of Sendeng-4 were 3.683-7.730， 2.391-6.952， 2 275.538-4 377.491， 2 699.188-3 537.924， 858.266-1 377.393， 3.366-11.003， 140.624-315.683，414.629-978.334， 285.501-1 510.457， 27.799-48.325， 3 625.415-6 309.563， 0.506-0.656， 442.337-649.283， 47.093-59.736， 12.942-15.822， 127.738-326.649 μg/g， respectively. According to the results of CA and PCA， 15 batches of samples could be clustered into two categories: S1-S3， S5-S6， S9-S10 and S13 were clustered into one category； S4， S7-S8， S11-S12， S14-S15 were clustered into one category. VIP values of geniposide， epicatechin， deacetylasperulosidic acid methyl ester and genipin-1-O- β-D-gentiobioside were all greater than 1. CONCLUSIONS HPLC-Q-Exactive-MS and HPLC-MS/MS techniques are employed for the qualitative and quantitative analysis of Sendeng-4. Through chemical pattern recognition analysis， four differential components are identified: geniposide， epicatechin， deacetylasperulosidic acid methyl ester， and genipin-1-O-β-D-gentiobioside.

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).

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*