[Background]Prenatal exposure to fine particulate matter(PM2.5)is closely associated with cortical damage and neuroinflammation in offspring.The cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)sig-naling 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 PM2.5-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 PM2.5-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 PM2.5 injury model.Using small interfering RNA(siRNA)technology,the KDM5A gene was silenced in BV2 cells exposed to PM2.5.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 al-terations in the cGAS-STING pathway. [Results]Compared with the control group,the total distance of offspring mice in the PM2.5 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 PM2.5 group exhibited disorga-nized 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 PM2.5 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 PM2.5-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 PM2.5,compared with the PM2.5+siNC group,the PM2.5+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 PM2.5-induced cortical damage in off-spring mice during pregnancy.

Liver fibrosis is a central pathological process driving the progression of chronic liver disease to cirrhosis and involves complex signaling networks across multiple cell types. Signal transducer and activator of transcription 3 (STAT3) serves as a signaling hub that integrates inflammatory, metabolic, and fibrogenic signals and exerts pleiotropic regulatory functions in liver fibrosis. STAT3 structure and subcellular localization provide the scaffold for signal encoding, whereas post-translational modifications (PTMs) alter STAT3 stability, dimerization, localization, transcriptional activity, and protein interactions. These regulatory states are further translated through direct transcriptional control, epigenetic mechanisms, non-coding RNA networks, signaling crosstalk, metabolic reprogramming, and oxidative stress into cell-specific phenotypes within the fibrotic microenvironment. Current evidence most consistently supports a pro-fibrotic role for STAT3 activation in HSC-centered fibrogenic programs, whereas several PTM-dependent, metabolic, and cell-protective mechanisms remain context-restricted or incompletely validated. Herein, we provide a structured narrative synthesis of STAT3 regulation in liver fibrosis, dissect the current status and challenges of targeted therapeutic strategies, and discuss how context-matched STAT3 modulation may inform future anti-fibrotic strategies.

Exposure to fine particulate matter (PM2.5) has been increasingly associated with neurodevelopmental disorders, yet the underlying molecular mechanisms remain poorly defined. KDM5A, a histone lysine demethylase implicated in cognitive regulation, has not been thoroughly investigated in the context of PM2.5-induced neurotoxicity. In this study, using an in vitro model of PM2.5-exposed hippocampal neurons, we demonstrated that KDM5A overexpression significantly ameliorates synaptic damage. Transcriptomic analysis identified Pin1 as a key downstream effector of KDM5A. Mechanistically, PM2.5 exposure led to KDM5A downregulation, resulting in increased H3K4me3 levels and upregulated Pin1 expression. Perturbing KDM5A or Pin1 expression altered synaptic protein levels, confirming their functional interplay in PM2.5-induced synaptic damage. ChIP-qPCR revealed co-enrichment of KDM5A and H3K4me3 at the Pin1 promoter. Furthermore, dual-luciferase reporter assays and demethylase-inactive KDM5A mutants confirmed that KDM5A represses Pin1 transcription via its demethylase activity. It is noteworthy that KDM5A primarily regulates Pin1's transcription via its histone demethylase activity, rather than through direct protein-protein interaction influencing Pin1 protein activity. Site-directed mutagenesis identified critical regulatory elements within the Pin1 promoter responsible for KDM5A-mediated suppression. Collectively, our findings suggest that PM₂.₅ may impair synaptic plasticity via the KDM5A–Pin1 axis, offering fresh insights into the potential mechanisms underlying pollution-related neurodevelopmental disorders.

BACKGROUND:Breast cancer is the most common malignancy that occurs in women. Due to the pain caused by the disease itself and the adverse reactions in the treatment process, breast cancer patients are prone to anxiety, depression, fear of recurrence, and other negative emotions, which seriously affect the quality of life. As a systematic stress reduction therapy, mindfulness-based stress reduction is widely applied to the treatment of breast cancer patients and has been found by a growing number of studies to relieve stress, regulate mood, and improve the state. However, due to the absence of recent research and uniform outcome measures, previous studies have failed to fully explain the role of mindfulness-based stress reduction in improving the quality of life in breast cancer patients. OBJECTIVE:We conducted a systematic review and meta-analysis to evaluate and compare the effects of mindfulness-based stress reduction therapy and standard care on the quality of life and psychological status of breast cancer patients. METHODS:We searched PubMed, Web of Science, Embase, China's National Knowledge Infrastructure and the Cochrane Central Registry of Controlled Trials up to July 2023 to identify candidate randomized clinical trials addressing the values of mindfulness-based stress reduction in breast cancer patients. RESULTS:A total of 1644 patients participated in 11 randomized controlled trials. The results of the meta-analysis showed that mindfulness-based stress reduction therapy can significantly reduce negative emotions such as perceived stress (MD = -1.46, 95%CI = -2.53 to -0.38, p = 0.03), depression (MD = -1.84, 95%CI = -3.99 to -0.30, p = 0.0004), anxiety (MD = -2.81, 95%CI = -5.31 to -0.32, p = 0.002), and fear of recurrence (MD = -1.27, 95%CI = -3.44 to 0.90, p = 0.0004). Mindfulness-based stress reduction therapy also has certain advantages in improving the coping ability (MD = 1.26, 95%CI = -3.23 to5.76, p = 0.03) and the emotional state (MD = -7.73, 95%CI = -27.34 to 11.88, p = 0.0007) of patients with breast cancer. CONCLUSION:Our analyses support that, compared with standard care, mindfulness-based stress reduction therapy can significantly improve patients' coping ability, reduce adverse emotions and improve patients' emotional states.

Postbiotics, as emerging products, were added to infant formula, but their safety and efficacy are unclear. To clarify this issue, we wrote this meta-analysis. We searched PubMed, Embase, Web of Science and ProQuest from its establishment to February 2023. The review was registered on PROSPERO database (CRD42022352405). The effects of infant formula with and without postbiotics were compared, and the incidence of serious adverse events (SAEs), digestive symptoms, concentration of stool secretory immunoglobulin A (SIgA), and growth and development indexes were analyzed. Nine randomized controlled trials with 2065 participants were included. The addition of postbiotics to infant formula was found to increase the concentration of stool SIgA ( P < 0.05) with very low certainty of evidence, without significantly impacting the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain and gastrointestinal disorders, the daily weight gain, the total gain in body length and the daily head circumference gain (all P > 0.05). Adding postbiotics to the formula is safe for infants, which would not increase the incidence of SAEs, infantile colic, flatulence, diarrhea, vomiting, abdominal pain, and gastrointestinal disorders, and could increase the concentration of stool SIgA. Impact Our study provides evidence that the addition of postbiotics to infant formula is safe but not effective. This is the first systematic review and meta-analysis of postbiotics. This study provides strong evidence for the safety of postbiotics and lays a foundation for related clinical trials.

[Background]Salidroside(SAL)has a protective effect on multiple organ systems.Exposure to fine particulate matter(PM2.5)in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health.The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. [Objective]To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. [Methods]Forty male C57BL/6 mice,aged 6 to 8 weeks,were randomly divided into four groups:a control group,an SAL group,a PM2.5 group,and an SAL+PM2.5 group,each containing 10 mice.In the SAL group and the SAL+PM2.5 group,the mice were administered SAL(60 mg·kg-1)by gavage,while in the control group and the PM2.5 group,sterile saline(10 mL·kg-1)was administered by gavage.In the PM2.5 group and the SAL+PM2.5 group,PM2.5 suspension(8 mg·kg-1)was intratracheally instilled,and in the control group and SAL group,sterile saline(1.5 mL·kg-1)was intratracheally administered.Each experiment cycle spanned 2 d,with a total of 10 cycles conducted over 20 d.Histopathological changes in the ileum tissue of the mice were observed after HE staining.Colon contents were collected for gut microbiota sequencing and short-chain fatty acids(SCFAs)measurements. [Results]The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue,while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration.Compared to the control group,the PM2.5 group showed decreased Shannon index(P<0.05)and increased Simpson index(P<0.05),indicating that the diversity of gut microbiota in this group was decreased;the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group(P<0.05)and decreased Simpson index(P<0.05),indicating that the di-versity of gut microbiota in mice intervened with SAL was increased.The principal coordinates analysis(PCoA)revealed a significant sep-aration between the PM2.5 group and the control group,while the separation trend was less evident among the control group,the SAL group,and the SAL+PM2.5 group.The unweighted pair-group method with arithmetic means(UPGMA)clustering tree results showed that the control group and the SAL group clustered together first,followed by clustering with the SAL+PM2.5 group,and finally,the three groups clustered with the PM2.5 group.The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased.Compared to the control group,the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas(P<0.05)and increased abundance of phylum Proteobacteria,genus Escherichia,genus Bacteroides,genus Prevotella,genus Enterococcus,and genus Proteus(P<0.05).Compared to the PM2.5 group,the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria,phylum Actinobacteria,genus Prevotella,and genus Proteus(P<0.05),and in-creased abundance of Candidatus_Saccharimonas(P<0.05).The PM2.5 group showed reduced levels of propionic acid,valeric acid,and hexanoic acid compared to the control group(P<0.05),while the SAL+PM2.5 group showed increased levels of propionic acid,isobutyric acid,butyric acid,valeric acid,and hexanoic acid compared to the PM2.5 group(P<0.05). [Conclusion]Exposure to PM2.5 can cause pathological alterations,microbial dysbiosis,and disturbing production of SCFAs in intestinal tissue in mice.However,SAL can provide a certain degree of protective effect against these changes.

ObjectiveThis study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis.MethodsSpecific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM2.5 group, SAL+PM2.5 group. On the first day, SAL was given by gavage, and on the second day, PM2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting.ResultsExposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1β, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway.ConclusionSAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

Prenatal environmental exposure could be an essential health risk factor associated with neurodevelopmental disorders in offspring. However, the exact mechanisms underlying the impact of prenatal PM2.5 exposure on offspring cognition remain unclear. In our recent study using a PM2.5 exposed pregnant mouse model, we observed significant synaptic dysfunction in the hippocampi of the offspring. Concurrently, the epigenetic regulator of KDM5A and the Shh signaling pathway exhibited decreased activities. Significantly, changes in hippocampal KDM5A and Shh levels directly correlated with PM2.5 exposure intensity. Subsequent experiments revealed a marked reduction in the expression of Shh signaling and related synaptic proteins when KDM5A was silenced in cells. Notably, the effects of KDM5A deficiency were reversed significantly with the supplementation of a Shh activator. Furthermore, our findings indicate that Shh activation significantly attenuates PM2.5-induced synaptic impairments in hippocampal neurons. We further demonstrated that EGR1, a transcriptional inhibitor, plays a direct role in KDM5A’s regulation of the Shh pathway under conditions of PM2.5 exposure. Our results suggest that the KDM5A’s inhibitory regulation on the Shh pathway through the EGR1 gene is a crucial epigenetic mechanism underlying the synaptic dysfunction in hippocampal neurons caused by maternal PM2.5 exposure. This emphasizes the role of epigenetic regulations in neurodevelopmental disorders caused by environmental factors.

Background:Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients' quality of life. Methods:We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs). Results:A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD] = -63.18, 95%CI = -91.73 to -34.62, P < .00001), TGAb content (MD = -68.56, 95%CI = -101.55 to -35.57, P < .00001), serum free triiodothyronine (FT3) content (MD = 0.74, 95%CI = 0.20 to 1.27, P < .00001), serum free thyroxine (FT4) content (MD = 1.10, 95%CI = 0.29 to 1.92, P < .00001), TSH content (MD = -2.16, 95%CI = -3.14 to -1.19, P < .00001) had a significant effect. Conclusion:Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH.

Elevated levels of respirable particulate matter (PM) have been strongly linked to disease incidence and mortality in population-based epidemiological studies. Berberine hydrochloride (BBR), an isoquinoline alkaloid found in Coptis chinensis, exhibits antipyretic, anti-inflammatory, and antioxidant properties. However, the protective effects and underlying mechanism of BBR against pulmonary fibrosis remain unclear. This study aimed to investigate the protective effect of BBR on lung tissue damage using a mouse model of PM2.5-induced pulmonary fibrosis. SPF grade C57BL/6 mice were randomly assigned to four groups, each consisting of 10 mice. The mice were pretreated with BBR (50 mg/kg) by gavage for 45 consecutive days. A tracheal drip of PM2.5 suspension (8 mg/kg) was administered once every three days for a total of 15 times to induce lung fibrosis. Moreover, the results demonstrated that PM2.5 was found to inhibit the PPARγ signaling pathway, increase ROS expression, upregulate protein levels of IL-6, IL-1β, TNF-α, as well as regulation of gene expression of STAT3 and SOCS3. Importantly, PM2.5 induced lung fibrosis by promoting collagen deposition, upregulating gene expression of fibrosis markers (TGF-β1, FN, α-SMA, COL-1, and COL-3), and downregulating E-cadherin expression. Remarkably, our findings suggest that these injuries could be reversed by BBR pretreatment. BBR acts as a PPARγ agonist in PM2.5-induced pulmonary fibrosis, activating the PPARγ signaling pathway to mitigate oxidative and inflammatory factor-mediated lung injury. This study provides valuable insights for the future prevention and treatment of pulmonary fibrosis.

Recent extensive evidence suggests that ambient fine particulate matter (PM2.5, with an aerodynamic diameter <= 2.5 mu m) may be neurotoxic to the brain and cause central nervous system damage, contributing to neurodevelopmental disorders, such as autism spectrum disorders, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and mental disorders, such as schizophrenia, depression, and bipolar disorder. PM2.5 can enter the brain via various pathways, including the blood-brain barrier, olfactory system, and gut-brain axis, leading to adverse effects on the CNS. Studies in humans and animals have revealed that PM2.5-mediated mechanisms, including neuroinflammation, oxidative stress, systemic inflammation, and gut flora dysbiosis, play a crucial role in CNS damage. Additionally, PM2.5 exposure can induce epigenetic alterations, such as hypomethylation of DNA, which may contribute to the pathogenesis of some CNS damage. Through literature analysis, we suggest that promising therapeutic targets for alleviating PM2.5-induced neurological damage include inhibiting microglia overactivation, regulating gut microbiota with antibiotics, and targeting signaling pathways, such as PKA/CREB/BDNF and WNT/beta -catenin. Additionally, several studies have observed an association between PM2.5 exposure and epigenetic changes in neuropsychiatric disorders. This review summarizes and discusses the association between PM2.5 exposure and CNS damage, including the possible mechanisms by which PM2.5 causes neurotoxicity.

BackgroundAlthough Alzheimer's disease (AD) mainly affects cognitive function, it is often accompanied by sleep disorders and psychobehavioral symptoms. These symptoms, including depression, agitation, and psychotic symptoms, are prominent hospitalization causes among patients with AD. Currently, relatively more research exists on light therapy for sleep disorders, while those on psychobehavioral symptoms are gradually increasing. However, no consensus exists on these results because of the vulnerability of light therapy to multiple factors, including light intensity and duration. Thus, further research investigating this aspect is warranted.ObjectiveTo evaluate the efficacy of light therapy in improving sleep disorders and psychobehavioural symptoms in patients with AD.MethodsIn this meta-analysis, relevant literature was searched in Embase, the Clinical Trials Registry, Web of Science, PubMed, and the Cochrane Library up to December 2022. Furthermore, a fixed-effects model was used for data analysis.ResultsFifteen randomized controlled trials involving 598 patients with AD were included. In the case of sleep disorders, our meta-analysis revealed that light therapy significantly improved sleep efficiency (MD = -2.42, 95% CI = -3.37 to -1.48, p < 0.00001), increased interdaily stability (MD = -0.04, 95% CI = -0.05 to -0.03, p < 0.00001), and reduced intradaily variability (MD = -0.07, 95% CI = -0.10 to -0.05, p < 0.00001). With respect to psychotic behavior, light therapy was found to alleviate depression (MD = -2.55, 95% CI = -2.98 to -2.12, p < 0.00001) as well as reduce agitation (MD = -3.97, 95% CI = -5.09 to -2.84, p < 0.00001) and caregiver burden (MD = -3.57, 95% CI = -5.28 to -1.87, p < 0.00001).ConclusionLight therapy leads to significant improvement in sleep and psychobehavioral symptoms and is associated with relatively fewer side effects in patients with AD, indicating its potential as a promising treatment option for AD.

PM2.5 is a harmful air pollutant currently threatening public health. It has been closely linked to increased morbidity of bronchial asthma and lung cancer worldwide. Salidroside (Sal), an active component extracted from Rhodiola rosea, has been reported to ameliorate the progression of asthma. However, there are few studies on the protective effect of salidroside on PM2.5-induced bronchial epithelial cell injury, and the related molecular mechanism is not clear. Here, we aimed to explore the protective effect and related mechanism of Sal on PM2.5 bronchial injury. We chose 50 μg/mL PM2.5 for 24 h as a PM2.5-induced cell damage model. After that BEAS-2B cells were pretreated with 40, 80, 160 µM Sal for 24 h and then exposed to 50 μg/mL PM2.5 for 24 h. We found that Sal pretreatment significantly inhibited the decrease of cell viability induced by PM2.5. Sal was effective in preventing PM2.5-induced apoptotic features, including Ca2+ overload, the cleavages of caspase 3, and the increases in levels of caspase 9 and Bcl-2-associated X protein (Bax), ultimately, Sal significantly inhibited PM2.5-induced apoptosis. Sal improved mitochondrial membrane potential, inhibited the release of cytochrome c from the mitochondria to cytoplasm. Sal alleviated ROS production, decreased the level of MDA, prevented the reduction of CAT, SOD and GSH-Px and increased the expression of NF-E2-related factor 2 (Nrf2), HO-1 and superoxide dismutase 1 (SOD1) in cells exposed to PM2.5. Furthermore, Sal improved the decrease of SIRT1 and PGC-1 α expression levels caused by PM2.5. In addition, inhibition of SIRT1 by EX527 (SIRT1 inhibitor) reversed the protective effects of Sal, including the decrease of ROS level, the increase of membrane potential level and the decrease of apoptosis level. Thus, Sal may be regarded as a potential drug to prevent PM2.5-induced apoptosis of bronchial epithelial cells and other diseases with similar pathological mechanisms.

Background: Preterm birth is associated with an increased risk of many complications, which is a main public health problem worldwide with social and economic consequences. Human milk from breast feeding has been proved to be the optimal nutrition strategy for preterm infants when available. However, the lack of human milk from mothers makes formula widely used in clinical practice. In recent years, donated breast milk has gained popularity as an alternative choice which can provide human milk oligosaccharides and other bioactive substances. Objective: We aimed to conduct a systematic review and meta-analysis to evaluate the nutritional effects of donated breast milk on preterm infants compared with formula. Method: In the present study, we searched Medline, Web of Science, Embase, clinicaltrials.gov, the China national knowledge infrastructure, and the Cochrane central register of controlled trials for candidate randomized controlled trials (RCTs). Results: A total of 1390 patients were enrolled in 11 RCTs and meta-analysis results showed that donated breast milk is also more advantageous in reducing the incidence of necrotizing enterocolitis (NEC, RR = 0.67, 95% CI = 0.48 to 0.93, p = 0.02), reducing the duration of parenteral nutrition (MD = −2.39, 95% CI = −3.66 to −1.13, p = 0.0002) and the time of full enteral feeding (MD = −0.33, 95% CI = −3.23 to 2.57, p = 0.0002). In comparison, formula significantly promotes the growth of premature infants, including their weight gain (MD = −3.45, 95% CI = −3.68 to −3.21, p < 0.00001), head growth (MD = −0.07, 95% CI = −0.08 to −0.06, p < 0.00001) and body length (MD = −0.13, 95% CI = −0.15 to −0.11, p < 0.00001), and reduces the time it takes for premature infants to regain birth weight (MD = 6.60, 95% CI = 6.11 to 7.08, p < 0.00001. Conclusion: Compared with formula, donated breast milk could significantly reduce the incidence of NEC, the duration of parenteral nutrition, and the time of full enteral feeding. Adding fortifiers in donated milk could make it as effective as formula in promoting the physical growth of premature infants.

Background: Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD. Methods: We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance. Conclusion: This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

OBJECTIVE:To investigate the damage of rat alveolar type II epithelial cells(RLE-6 TN) caused by air fine particulate matter(PM_(2.5)) and its related mechanism.METHODS:PM_(2.5) in the atmosphere of Weifang City in 2020 was collected and cell culture medium was used to prepare particulate suspension. RLE-6 TN cells were exposed to different concentrations(25, 50, 100, 200, 400 μg/mL) of particulate matter suspensions for 24 h. The morphological changes of RLE-6 TN cells were observed under inverted microscope, and the cell viability was determined by MTT method. The concentration of lactate dehydrogenase(LDH) in cell supernatant was determined by microplate method. DCFH-DA, Annexin V-FITC/PI, JC-1 probe and laser confocal fluorescence intensity were used to determine the levels of reactive oxygen species(ROS), apoptosis and mitochondrial membrane potential. Total superoxide dismutase(T-SOD), glutathione(GSH) and malondialdehyde(MDA) contents and activity levels in cells were determined by colorimetric method. Caspase-3 and Caspase-9 kit were used to detect the relative expression activity of apoptosis proteins.RESULTS:PM_(2.5) could lead to morphological changes of RLE-6 TN cells, enlarged cell space and decreased cell viability. Compared with the control group, there were statistically significant differences in each dose group(P&lt;0.05). LDH concentration in the supernatant of ≥50 μg/mL infected group increased, and LDH concentration was ≥(377.82±29.84), which was significantly different from that of the control group(278.51±23.76)(P&lt;0.05). The result of laser confocal detection of ROS showed that the intracellular green fluorescence increased gradually in the ≥50 μg/mL group, and the relative fluorescence intensity was ≥(2.77±0.18), which was statistically significant compared with the control group(P&lt;0.05). The level of apoptosis was significantly increased compared with the control group(P&lt;0.05). The level of mitochondrial membrane potential decreased gradually, and the level of mitochondrial membrane potential in the ≥25 μg/mL group was ≤(4.22±0.45), which was statistically different from that in the control group(6.16±0.49)(P&lt;0.05). PM_(2.5) could reduce the levels of T-SOD and GSH, and the levels of T-SOD and GSH in ≥50 μg/mL exposed group were ≤(14.67±0.49) and ≤(433.29±39.24), respectively, significantly lower than those in control group((16.58±0.60) and(542.90±45.06))(P&lt;0.05). MDA level increased with the increase of PM_(2.5) concentration. Compared with the control group(1.15±0.19), MDA level in ≥50 μg/mL exposed group was ≥(1.72±0.13), with statistical significance(P&lt;0.05). The activity levels of Caspase-3 and Caspase-9 increased in ≥100 μg/mL group, and the activity levels were ≥(1.62±0.27) and ≥(1.23±0.06), respectively, compared with the control group, the differences were statistically significant(P&lt;0.05).CONCLUSION:Exposure to a certain concentration of PM_(2.5) can induce oxidative stress of rat alveolar type II epithelial cells, reduce the membrane potential, and eventually lead to cell apoptosis.

目的:探讨孕期B族维生素(VitB)干预是否改善了PM2.5暴露所致的孕鼠抑郁样行为及可能的表观遗传学机制.方法:采用气管雾化的方式建立孕期PM2.5损伤模型,同步进行B族维生素干预.将孕鼠随机分为PBS对照组、PM2.5暴露组和VitB干预组.采用旷场实验分析孕鼠抑郁样行为的变化;分离孕鼠大脑皮层,采用NeuN免疫荧光染色及高尔基染色检测神经元的损伤情况,Western blot检测突触蛋白的表达变化;采用RT-qPCR、Western blot和免疫荧光双标染色检测孕鼠大脑皮层KDM5家族的表达变化和分布情况,及组蛋白H3K4的甲基化水平.结果:B族维生素干预能明显改善PM2.5暴露所致孕鼠的抑郁程度,中央区活动时间显著延长(P<0.05),中央区活动距离和旷场运动总距离增多(P<0.05);B族维生素干预能缓解PM2.5导致的孕鼠大脑皮层神经元损伤,树突形态的复杂性得到保护,突触相关蛋白——突触小泡蛋白、生长相关蛋白43和突触后致密蛋白95水平显著回升(P<0.05);大脑皮层KDM5A、KDM5B和KDM5C的mRNA和蛋白水平均显著升高(P<0.05),组蛋白H3K4me3的蛋白水平明显得到纠正;大脑皮层KDM5A+/NeuN+、KDM5B+/NeuN+和KDM5C+/NeuN+双阳性神经元明显增多,大脑皮层椎体神经元恢复至正常.结论:孕期给予B族维生素干预,可以通过上调KDM5纠正大脑皮层组蛋白的甲基化水平,从而减轻PM2.5造成的神经元损伤及孕鼠抑郁样行为.