Background Prenatal exposure to fine particulate matter (PM_2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM_2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM_2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM_2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM_2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM_2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM_2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM_2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM_2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM_2.5, compared with the PM_2.5+siNC group, the PM_2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM_2.5-induced cortical damage in offspring mice during pregnancy.

Malignant obstructive jaundice is a severe pathophysiological disorder characterized primarily by hyperbilirubinemia secondary to biliary obstruction.To mitigate the adverse effects of hyperbilirubinemia and reduce postoperative complications,preoperative biliary drainage(PBD)has long been employed as a perioperative management strategy.Nevertheless,whether PBD confers definitive clinical benefits remains a subject of considerable debate.This review systematically summarizes the current literature,with particular emphasis on the indications,approaches,and clinical value of PBD in relation to obstruction at different anatomical sites,aiming to provide evidence-based guidance for surgical decision-making in patients with malignant obstructive jaundice.

Objective To investigate the function of Ring finger protein 13(RNF13)in cerebral ischemia reperfusion injury(CIRI),and its mechanism.Methods The mouse middle cerebral artery embolization and primary neuron oxygen-glucose depri-vation and reoxygenation were used as disease models.The CRISPR/Cas9 gene knockout technique,immunohistochemical stai-ning,immunofluorescence staining,Western blot and lipid peroxidation detection were used to evaluate the regulatory effect and molecular mechanism of RNF13 on ferroptosis in CIRI.Student's t test was used for the comparison of two samples,and one-way analysis of variance was used for the comparison of multiple samples.Results The expression levels of RNF13 protein in mice and primary neurons were upregulated during CIRI.After knockout of RNF13,ferritin heavy chain 1(Fth1)and ferritin light chain(Ftl)were downregulated,and the content of free ferrous ions and the accumulation of lipid peroxides in mice brain tissues were promoted,leading to ferroptosis aggravation and neurological impairments.Overexpression of RNF13 protected a-gainst ferroptosis by reducing the production of free ferrous and lipid peroxides in neurons.Conclusion RNF13 alleviates fer-roptosis in neurons after CIRI,and the effect is induced by Fth1.

Malignant obstructive jaundice is a severe pathophysiological disorder characterized primarily by hyperbilirubinemia secondary to biliary obstruction.To mitigate the adverse effects of hyperbilirubinemia and reduce postoperative complications,preoperative biliary drainage(PBD)has long been employed as a perioperative management strategy.Nevertheless,whether PBD confers definitive clinical benefits remains a subject of considerable debate.This review systematically summarizes the current literature,with particular emphasis on the indications,approaches,and clinical value of PBD in relation to obstruction at different anatomical sites,aiming to provide evidence-based guidance for surgical decision-making in patients with malignant obstructive jaundice.

Objective To investigate the function of Ring finger protein 13(RNF13)in cerebral ischemia reperfusion injury(CIRI),and its mechanism.Methods The mouse middle cerebral artery embolization and primary neuron oxygen-glucose depri-vation and reoxygenation were used as disease models.The CRISPR/Cas9 gene knockout technique,immunohistochemical stai-ning,immunofluorescence staining,Western blot and lipid peroxidation detection were used to evaluate the regulatory effect and molecular mechanism of RNF13 on ferroptosis in CIRI.Student's t test was used for the comparison of two samples,and one-way analysis of variance was used for the comparison of multiple samples.Results The expression levels of RNF13 protein in mice and primary neurons were upregulated during CIRI.After knockout of RNF13,ferritin heavy chain 1(Fth1)and ferritin light chain(Ftl)were downregulated,and the content of free ferrous ions and the accumulation of lipid peroxides in mice brain tissues were promoted,leading to ferroptosis aggravation and neurological impairments.Overexpression of RNF13 protected a-gainst ferroptosis by reducing the production of free ferrous and lipid peroxides in neurons.Conclusion RNF13 alleviates fer-roptosis in neurons after CIRI,and the effect is induced by Fth1.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Background and objective Current studies suggest that for early-stage lung cancers with a component of ground-glass opacity measuring ≤2 cm,sublobar resection is suitable if it ensures adequate margins.However,lobectomy may be necessary for some cases to achieve this.The aim of this study was to explore the impact of size and depth on surgical techniques for wedge resection,segmentectomy,and lobectomy in early-stage lung cancer ≤2 cm,and to determine methods for ensuring a safe resection margin during sublobar resections.Methods Clinical data from 385 patients with early-stage lung can-cer ≤2 cm,who underwent lung resection in 2022,were subject to a retrospective analysis,covering three types of procedures:wedge resection,segmentectomy and lobectomy.The depth indicator as the OA value,which is the shortest distance from the inner edge of a pulmonary nodule to the opening of the corresponding bronchus,and the AB value,which is the distance from the inner edge of the nodule to the pleura,were measured.For cases undergoing lobectomy and segmentectomy,three-dimensional computed tomography bronchography and angiography(3D-CTBA)was performed to statistically determine the number of subsegments required for segmentectomy.The cutting margin width for wedge resection and segmentectomy was recorded,as well as the specific subsegments and their quantities removed during lung segmentectomy were documented.Results In wedge resection,segmentectomy,and lobectomy,the sizes of pulmonary nodules were(1.08±0.29)cm,(1.31±0.34)cm and(1.50±0.35)cm,respectively,while the depth of the nodules(OA values)was 6.05(5.26,6.85)cm,4.43(3.27,5.43)cm and 3.04(1.80,4.18)cm for each procedure,showing a progressive increasing trend(P＜0.001).The median resec-tion margin width obtained from segmentectomy was 2.50(1.50,3.00)cm,significantly greater than the 1.50(1.15,2.00)cm from wedge resection(P＜0.001).In wedge resections,cases where AB value＞2 cm demonstrated a higher proportion of cases with resection margins less than 2 cm compared to those with margins greater than 2 cm(29.03％vs 12.90％,P=0.019).When utilizing the size of the nodule as the criterion for resection margin,the instances with AB value＞2 cm continued to show a higher proportion in the ratio of margin distance to tumor size less than 1(37.50％vs 17.39％,P=0.009).The median number of subsegments for segmentectomy was three,whereas lobectomy cases requiring segmentectomy involved five subsegments(P＜0.001).Conclusion The selection of the surgical approach for lung resection is influenced by both the size and depth of pulmonary nodules.This study first confirms that larger portions of lung tissue must be removed for nodules that are deeper and larger to achieve a safe margin.A distance of ≤2 cm from the inner edge of the pulmonary nodule to the nearest pleura may be the ideal indication for performing wedge resection.

Objective To investigate the role of macrophages in the process of fine particulate matter (PM2.5)exposure induced damage to pulmonary blood-air barrier.Methods Eighteen male BALB/C mice (aged of 10 weeks,weighing 24～27 g)were randomly divided into control group and low-and high-dose PM2.5 exposure groups (receiving 1 .8 and 16.2 mg/kg,respectively),with 6 mice in each group.The control group received tracheal instillations of normal saline on days 1,4,and 7,whereas the exposure groups were administered corresponding dose of PM2.5 exposure at the same time points.In 24 h after last exposure,pathological changes in the lung tissues were observed,and the contents of total protein (TP ),lactate dehydrogenase (LDH ),and alkaline phosphatase (AKP ) in bronchoalveolar lavage fluid (BALF ),and F4/80 protein level in lung tissue were measured to evaluate the blood-air barrier damage and macrophage infiltration within the lung tissues.Additionally,an in vitro model of the blood-air barrier was established using A549 alveolar epithelial cells and EA.hy926 vascular endothelial cells.In combination with a THP-1 macrophage model,the supernatant PM2.5 supernatant,macrophage supernatant,and PM2.5-macrophage supernatant were incubated with the barrier model for 24 h,respectively.Transmembrane electrical resistance (TEER),sodium fluorescein permeability of the barrier model,and LDH release from the barrier cells were measured to ascertain the extent of macrophage-mediated enhancement in barrier damage induced by PM2.5 exposure.Furthermore,the expression of inflammatory cytokines,such as TNF-α,IL-1β,IL-6,and IL-8 in the macrophages after PM2.5 exposure was analyzed with quantitative real-time PCR (qPCR)and enzyme-linked immunosorbent assay (ELISA).Results PM2.5 exposure induced lung tissue damage in mice in a dose-dependent manner,significantly elevated the contents of TP,LDH and AKP in the BALF and caused marked infiltration of macrophages into the lung tissue,especially the high-dose exposure when compared with the mice from the control group (P<0.01 ).In vitro barrier model exposure experiments showed that in comparison with the treatment of 150 and 300 μg/mL PM2.5 and macrophage supernatant,the same doses of PM2.5-macrophage supernatant resulted in notably decreased TEER and significantly enhanced permeability in the barrier model (P<0.01 ),and markedly increased LDH release from epithelial and endothelial barrier cells (P<0.01 ).Additionally,the exposure of 150 and 300μg/mL PM2.5 led to a significant up-regulation of TNF-α,IL-1β,IL-6,and IL-8 in the macrophages (P<0.01 ).Conclusion Macrophages deteriorate PM2.5-induced functional impairment of the pulmonary blood-air barrier.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Long non-coding RNA(lncRNA)is a class of endogenous non-coding RNA with a length of more than 200 nt.Due to lack of open reading frame(ORF),they lack the ability to directly encode proteins,but they play a crucial role in gene regulation.They are widely involved in epigenetics,transcription,translation,modification and degradation,thereby affecting the life activities of the body,and their expression imbalance is closely related to the occurrence and development of diseases.Therefore,analyzing the inherent characteristics of lncRNA and revealing its intrinsic role can not only deepen our understanding of human physiological and pathological processes,but also provide new ideas and potential solutions for the diagnosis,prevention and treatment of diseases.So as to provide references for the related research of lncRNAs.