Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (A_e) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10^-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

OBJECTIVE: To compare the clinical effects of pulpotomy with two kinds of calcium silicate materials, and to evaluate the formation of dentin bridge and pulp calcification after pulpotomy of adult permanent teeth. METHODS: Patients who visited the General Department of Peking University School and Hospital of Stomatology from November 2017 to September 2019 and planned for pulpotomy on permanent premolars and molars with carious exposed pulp were selected. They were randomly divided into two groups. Bioceramic putty material iRoot BP (iRoot group, n=22) and mineral trioxide aggregate MTA (MTA group, n=21) were used as pulp capping agents, respectively. The patients were recalled after one year and two years. The clinical efficacy, dentin bridge index (DBI) and pulp calcification index (PCI) were recorded. Blinding method was used for the patients and evaluators. RESULTS: There was no significant difference in gender, mean age, dentition and tooth position between the two groups (P>0.05). Seven cases were lost during the first year (4 cases in iRoot group and 3 cases in MTA group). In the iRoot group, 1 case had transient sensitivity at the time of 1-year follow-up. The cure rate of the two groups was 100% at the time of 2-year follow-up. The proportion of dentin bridge formation was 38.9% one year after operation, 55.6% two years after operation. The proportion of partial or even complete disappearance of root canal image was 5.6% before operation, 38.9% and 55.6% one and two years after operation, respectively. The difference was statistically significant by rank sum test (P < 0.05). There was no significant difference in dentin bridge formation and pulp calcification between the two groups (P < 0.05). DBI and PCI after operation was as the same as those before operation (44.4% cases of DBI and 25% cases of PCI) or gradually increased (55.6% cases of DBI and 75% cases of PCI). Spearman's nonparametric correlation analysis showed that age was positively correlated with preoperative pulp calcification index (PCI0, P < 0.05), but not with the dentin bridge index (DBI1, DBI2), pulp calcification index (PCI1, PCI2) and the degree of change (DBI2 vs. DBI1, PCI1 vs. PCI0, PCI2 vs. PCI0) 1-year and 2-year after operation (P>0.05). CONCLUSION According to this study, good clinical effects were obtained within 2-year after pulpotomy of adult permanent teeth with MTA and iRoot. In some cases, the root canal system had a tendency of calcification aggravation, and there was no statistical difference in the development of this trend between the two groups.
Humans ; Adult ; Pulpotomy/methods* ; X-Rays ; Calcium Compounds/therapeutic use* ; Dentition, Permanent ; Molar/surgery* ; Treatment Outcome ; Silicates/therapeutic use* ; Aluminum Compounds/therapeutic use* ; Oxides ; Drug Combinations ; Dental Pulp Capping

ObjectiveTo compare the nocturnal erectile function between SRPE patients and normal people. MethodsFrom July 1st， 2019 to December 15th， 2022， a clinical comparative study was conducted on 29 SRPE patients （experimental group） and 58 volunteers （control group） who visited our urology department. The Rigiscan System was used to monitor sleep monitoring time， the number of nocturnal erections and the rigidity， duration and circumference growth of the penis when the erection reached 60%～79% and 80%～100%， respectively. The patients and volunteers were asked to make written records when they woke up， and then the total number of awakenings and the number of awakenings when the penis erection reached 60% and 80% were compared between the two groups. ResultsAge was eliminated by matching. There was no statistically significant difference in sleep monitoring time， rigidity， circumference growth and duration of the penis when the erection reached 60%～79% and 80%～100%. between the two groups. In terms of sleep， there was a statistically significant difference in the total number of awakenings between the two groups［3（2 ~ 4）vs 0（0 ~ 0），P<0.01］ .And the same was true for the number of awakenings when the penis erection exceeded 60%～79% ［1（0 ~ 1）vs 0（0 ~ 0），P<0.01］and 80%～100% ［2（1 ~ 3）vs 0（0 ~ 0），P<0.01］. ConclusionRigiscan monitoring showed that there was no difference between SRPE patients and normal male in nocturnal penile erection function. Painful awakening usually occurs when the penis erection reaches 60%～79% or 80%～100%， which reveals that SRPE may be caused by abnormal sensation of nocturnal erections or pain sensitivity in some of these patients.

In order to achieve the goal of integration, homogeneity, a net and a center of medical groups in Hainan province, Hainan province built an integrated management information platform of urban medical alliances and county medical communities based on projects such as the provincial three medical linkage information platform in February 2022. The overall architecture of the medical alliance and medical community platform was divided into system integration layer, data center layer, service layer and application layer. The service layer included four major systems: unified operation management platform, business center, performance evaluation management platform and comprehensive supervision subsystem, which was the core hub connecting the data center layer and application layer, and also was the unified operation and closed-loop management platform of the medical alliance and medical community. As of November 2022, the platform had covered 31 medical alliances or medical communities in 19 cities and counties of Hainan province, achieving information exchange, personnel interaction, resource sharing, business collaboration, and data integration among member units, narrowing the gap between urban and rural medical and health services, which had preliminarily achieved homogeneous management of the medical alliances and medical communities throughout the province, for a reference for the integrated management of medical alliances and medical communities within the regional scope of China.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.