ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

AIM: To investigate the current status of retinopathy of prematurity(ROP)in premature infants in Xiamen and analyze its influencing factors, aiming to provide a scientific basis for clinical treatment and preventive strategies.METHODS: A retrospective study was conducted on the case data of 363 preterm infants with a gestational age of <32 wk who underwent fundus examination at Xiang'an Hospital of Xiamen University from February 11, 2020 to February 25, 2023. The incidence of ROP was statistically analyzed based on the screening results. All premature infants were divided into ROP group(37 cases, 64 eyes)and non-ROP group(326 cases, 652 eyes). General clinical data and perinatal-related information of the two groups were compared, and multivariate Logistic regression analysis was used to identify factors influencing the occurrence of ROP in premature infants.RESULTS: A total of 363 premature infants were included in this study. The fundus screening results showed that a total of 37 cases(64 eyes)of premature infants were detected with ROP, including 10 cases(10 eyes)monocular and 27 cases(54 eyes)binocular, with an overall incidence of 10.2%(37/363). The severity was determined according to the ROP international classification standard(ROP is divided into 5 stages, with stage I being the least severe and stage V the most severe). Among the 64 eyes, 30 eyes(46.9%)were in stage I, 20 eyes(31.3%)were in stage II, 10 eyes(15.6%)were in stage III, 4 eyes(6.3%)were in stage IV, and there were no cases in stage V. By comparing the clinical data of the two groups, no significant differences were found in gender, mode of delivery, singleton or multiple births, premature rupture of membranes, history of asphyxia, patent ductus arteriosus(PDA), or neonatal respiratory distress syndrome(NRDS)between the two groups(all P>0.05). However, premature infants in the ROP group had significantly younger gestational age and lower birth weight compared to those in the non-ROP group(all P<0.05). Additionally, the ROP group had higher proportions of longer hospital stays, bronchopulmonary dysplasia(BPD), neonatal sepsis, anemia, oxygen therapy for more than 1 wk, oxygen concentration above 40%, and blood transfusion treatment(all P<0.05). Multivariate Logistic regression analysis revealed that combined neonatal sepsis(OR=166.985, 95% CI: 35.239-791.277, P<0.001), anemia(OR=8.111, 95% CI: 2.064-31.871, P=0.003), oxygen use time >1 wk(OR=10.216, 95% CI: 2.543-41.039, P=0.001), oxygen therapy concentration >40%(OR=7.647, 95% CI: 1.913-30.566, P=0.004), and receiving blood transfusion therapy(OR=5.879, 95% CI: 1.412-24.470, P=0.015)were the main risk factors affecting the occurrence of ROP in preterm infants, and the higher birth weight of preterm infants was a protective factor for ROP(OR=0.093, 95% CI: 0.022-0.394, P=0.001).CONCLUSION: The incidence of ROP in premature infants is relatively high, and there are multiple influencing factors. Low birth weight, neonatal sepsis, anemia, oxygen therapy, and blood transfusion treatment are high-risk factors for ROP in premature infants. Clinical attention should be given to such infants, and fundus screening should be conducted in a standardized manner to provide early treatment, thereby further reducing the risk of ROP in premature infants.

Total-body PET/CT, with its long axial field of view and high sensitivity detector, has shown potential for reducing the dose of radiopharmaceuticals. However, pediatric patients are significantly more sensitive to radiation and have a higher long-term cancer risk than adults, posing fundamental challenges for dose management in PET/CT examinations for these patients. In this article, the technical characteristics of total-body PET/CT and its radiation exposure status in children were systematically analyzed. The radiation exposure could be controlled by the following optimization strategies: adjusting the CT exposure parameters, optimizing the scanning mode, adding reconstruction algorithm, and reducing the injected dose of radioactive tracer. By addressing both external and internal radiation during the PET/CT scanning process, the overall radiation dose received by pediatric patients can be reduced within a certain range. In addition, this article also discusses the technical differences between “total-body” and “whole-body” concepts, and emphasizes that the future optimization of radiation dose in pediatric PET/CT should be realized by integration of personalized scanning protocols. Through reasonable management of scanning protocols and processes, low-dose and high-quality PET/CT imaging can be achieved in clinical environments, thus maximizing protection of pediatric patient health while minimizing the risks associated with ionizing radiation exposure.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Diabetic kidney disease (DKD) with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression. Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials. In this study, we integrated large-scale plasma proteomics, genetic-driven causal inference, and experimental validation to identify prioritized targets for DKD using the UK Biobank (UKB) and FinnGen cohorts. Among 2844 diabetic patients (528 with DKD), we identified 37 targets significantly associated with incident DKD, supported by both observational and causal evidence. Of these, 22% (8/37) of the potential targets are currently under investigation for DKD or other diseases. Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4 (IGFBP4), family with sequence similarity 3 member C (FAM3C), and prostaglandin D2 synthase (PTGDS)-were associated with a 4.35, 3.51, and 3.57-fold increased likelihood of developing DKD, respectively. In addition, population-level protein-altering variants (PAVs) analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD, through the classic NLR family pyrin domain containing 3 (NLRP3)-caspase-1-gasdermin D (GSDMD) apoptotic axis. Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

ObjectiveTo study the correlation between the content of active ingredients of Aurantii Fructus in different main production areas and soil factors， so as to provide a theoretical basis for implementing ecological regulation of soil， improving the quality of Aurantii Fructus， and revealing the origin of genuine medicinal materials. MethodThe content of naringin， neohesperidin， total flavonoids， volatile oil， total nitrogen， total phosphorus， total potassium， and 17 soil factor-related indicators in 25 batches of Aurantii Fructus from different production areas were determined. The main soil factors affecting the content of active ingredients of Aurantii Fructus were analyzed by Pearson correlation analysis， principal component analysis， and grey correlation analysis. ResultThe pH value of the soil is between 4.83 and 8.21， and the soil is weakly acidic and neutral in general. Soil fertility exceeds the average. Pearson correlation analysis shows that the soil factors most related to the four active ingredients of Aurantii Fructus are total phosphorus， available copper， available zinc， exchangeable magnesium， available sulfur， available phosphorus， and available molybdenum. Principal component analysis shows that total nitrogen， alkali-hydrolyzable nitrogen， organic matter， available phosphorus， and available zinc are the main characteristic factors in soil. Grey correlation analysis shows that the main soil factors affecting the active ingredients of Aurantii Fructus are total phosphorus， total nitrogen， available zinc， available copper， exchangeable magnesium， and pH. ConclusionIn the cultivation of Aurantii Fructus， the medicinal material quality of Aurantii Fructus could be improved by adjusting the level of beneficial factors in the soil and improving the soil texture.

Objective:To deeply analyze the efficiency of health resource allocation and output insufficiency in Jiangsu Province,and to understand the efficiency and differences of resource allocation in prefecture-level cities,so as to provide references for improving the efficiency of health resource allocation.Methods:The static and dynamic efficiencies of health resource allocation in 13 cities in Jiangsu Province were analyzed using DEA-BCC and Malmquist-DEA,and the distribution of output-deficient cities was plotted using a two-dimensional matrix diagram.Results:From a static perspective,the increase in scale efficiency leads to an increase in overall efficiency,but only one-sixth is fully efficient;from a dynamic perspective,technological progress is a key limiting factor in the increase of total factor productivity;and only 2 cities fall into the zero-output-deficiency region.Conclusion:Health resources in Jiangsu Province are characterized by low overall efficiency,large regional differences,and stagnant technological progress,so it is necessary to improve the efficiency of health resource allocation by emphasizing innovation,promoting technological progress,and classifying and guiding.