This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.

Sexual dimorphism in the brain underlies behavioral differences between sexes. The bed nucleus of the stria terminalis (BNST) is a complex nucleus that differs between males and females, but the sexual dimorphism in cytoarchitecture and the connectome of its oval subdivision (ovBNST) remains largely unexplored. By combining snRNA-seq and transgenic labeling, we found a higher density of ovBNST proenkephalin (ovBNST^PENK) neurons in male than female mice. Anatomically, we virally mapped the efferents and afferents of ovBNST^PENK neurons, finding reciprocally dimorphic connections with the hypothalamus and striatum. Gene enrichment analysis suggests that ovBNST^PENK neurons are modulated by the upstream dopamine pathway. Functionally, by applying caspase-3-mediated depletion of ovBNST^PENK neurons, we found that loss of these neurons enhanced locomotor activity in male but not female mice, without altering the anxiety-like phenotypes in either sex. Our study may pave the way for a better understanding of the anatomical and functional profiles of ovBNST^PENK neurons from a sexually dimorphic perspective.
Animals ; Male ; Female ; Septal Nuclei/physiology* ; Sex Characteristics ; Neurons/physiology* ; Enkephalins/metabolism* ; Mice ; Mice, Transgenic ; Protein Precursors/metabolism* ; Mice, Inbred C57BL ; Neural Pathways/physiology*

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective To compare the hepatic lipid droplet metabolism in normal BKS-db/m mice and BKS-db/db mice,a model of type 2 diabetes mellitus (T2DM),and to investigate the characteristics of hepatic lipid droplet metabolism and the molecular mechanisms underlying the imbalance of metabolic homeostasis at the level of lipid droplet synthesis and lipid droplet catabolism in db/db mice. Methods Eight SPF 8 weeks BKS-db/m and 8 BKS-db/db mice were used in this study. The lipid metabolism level was tested. Oil red and HE staining was used to evaluate the degree of liver lipid deposition,and immunofluorescence staining and Western blot was used to observe the level of hepatic lipid droplet catabolism and metabolism. Results The body weight,liver weight,liver index,FPG,AUC of the OGTT,AUC of the ITT,TG,TC,HDL-C,LDL-C,FFA and SREBP1 positive fluorescence area and nuclear translocation were higher in db/db group than in db/m group (P<0.05). The lipophagia level of primary hepatocytes was higher in db/db group than in db/m group (P<0.05). Compared with the db/m group,the expressions of SREBP1,SCD1,PLIN2,LC3,LAMP2A and ATGL protein increased(P<0.05),while the expression of p-ACC/ACC protein decreased in the db/db group(P<0.05). Conclusions Compared with normal mice,T2DM mice had dyslipidemiaand marked hepatocellular lipid deposition.Although lipid droplet lipolysis and lipophagy were enhanced and catabolism was significant,the lipid droplet metabolism was in a state of imbalance between synthesis and catabolism,and the synthesis of lipid droplets was greater than that of catabolism,which led to the aggregation of hepatocellular lipids.

Objective To compare the hepatic lipid droplet metabolism in normal BKS-db/m mice and BKS-db/db mice,a model of type 2 diabetes mellitus (T2DM),and to investigate the characteristics of hepatic lipid droplet metabolism and the molecular mechanisms underlying the imbalance of metabolic homeostasis at the level of lipid droplet synthesis and lipid droplet catabolism in db/db mice. Methods Eight SPF 8 weeks BKS-db/m and 8 BKS-db/db mice were used in this study. The lipid metabolism level was tested. Oil red and HE staining was used to evaluate the degree of liver lipid deposition,and immunofluorescence staining and Western blot was used to observe the level of hepatic lipid droplet catabolism and metabolism. Results The body weight,liver weight,liver index,FPG,AUC of the OGTT,AUC of the ITT,TG,TC,HDL-C,LDL-C,FFA and SREBP1 positive fluorescence area and nuclear translocation were higher in db/db group than in db/m group (P<0.05). The lipophagia level of primary hepatocytes was higher in db/db group than in db/m group (P<0.05). Compared with the db/m group,the expressions of SREBP1,SCD1,PLIN2,LC3,LAMP2A and ATGL protein increased(P<0.05),while the expression of p-ACC/ACC protein decreased in the db/db group(P<0.05). Conclusions Compared with normal mice,T2DM mice had dyslipidemiaand marked hepatocellular lipid deposition.Although lipid droplet lipolysis and lipophagy were enhanced and catabolism was significant,the lipid droplet metabolism was in a state of imbalance between synthesis and catabolism,and the synthesis of lipid droplets was greater than that of catabolism,which led to the aggregation of hepatocellular lipids.

Objective:To establish a digital droplet RT-PCR(dRT-PCR) method for Hepatitis A virus (HAV), and compare it with Real time RT-PCR(RT-qPCR) method, and select the best method for detecting hepatitis A virus in strawberry.Methods:Extract HAV vaccine RNA, optimize the reaction conditions of dRT-PCR and evaluate its specificity; Alkaline elution -PEG concentration method was used to extract nucleic acid from strawberry samples. At the same time, dRT-PCR and RT-qPCR method were used to detect the sensitivity and inhibition rate of HAV vaccine RNA in pure water and strawberry matrix, and the recovery rate of HAV in artificially contaminated strawberry was compared, which was applied to the detection of commercially available samples.Results:The optimal annealing temperature for dRT-PCR reaction was 60 ℃, and the optimal concentrations of primers and probes were 0.4 μmol/L、0.4 μmol/L and 0.2 μmol/L, with good specificity. There is no significant difference in sensitivity between the two method in detecting HAV vaccine RNA in pure water and strawberry matrix. The inhibition rate of dRT-PCR is low. The recovery rates of dRT-PCR and RT-qRCR in the detection of strawberry samples contaminated with HAV at higher concentrations were 12.90±0.006% and 30.12±0.02%, respectively. The recovery rates of lower concentrations of HAV contaminated strawberry samples were 18.27±0.07% and 10.85±0.03%, respectively, and the difference was statistically significant ( P<0.05). When strawberry samples on the market were tested, the result of both method were negative. Conclusions:The sensitivity of dRT-PCR method established in this study is not significantly different from that of RT-qPCR in detecting HAV RNA in different substrates, but dRT-PCR has good tolerance to PCR reaction inhibitors and high recovery rate when detecting low concentration HAV. Both detection method can be used for quantitative detection of hepatitis A virus in strawberry, and can be selected according to the actual situation.

Objective:To provide a basis for its diagnosis and treatment for clinicians by analyzing the clinical manifestations, imaging features and surgical efficacy of primary intraspinal paraganglioma.Methods:The clinical data of 6 patients with intraspinal paraganglioma from April 2014 to January 2021 in Xiangyang Central Hospital were retrospectively analyzed, and all patients were treated with microsurgery via a posterior median approach.Results:All 6 patients achieved total tumor resection, and the postoperative pathological diagnosis was paraganglioma. Among them, 1 patient′s tumor located inside and outside the cervical spinal canal without destruction of the vertebral body; 1 patient′s tumor located lumbosacral canal with destruction of the vertebral body; the others 4 patients′ tumor located within the lumbar spinal canal. The patients were followed up for 12 to 120 months after surgery, with a median follow-up time of 61.5 months. MRI examination was performed at the last follow-up, and no recurrence was observed. The patients underwent MRI examination at the last follow-up, and none of the patients recurred.Conclusions:The intraspinal paraganglioma is a rare tumor, and nonfunctional benign tumors are predominant. Its clinical and imaging manifestations lack specificity and are often difficult to diagnose before surgery. Surgical resection, especially complete resection, has a better prognosis, and the effectiveness of adjuvant therapy is uncertain.