ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription（TYTZP） against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley （SD） rats were randomly divided into sham group， model group， ticagrelor group （32.4 mg·kg^-1）， RU320521 （RU.521cGAS inhibitors） group （5 mL·kg^-1）， groups of TYTZP with low dose （3.6 g·kg^-1）， medium dose （7.2 g·kg^-1）， and high dose （14.4 g·kg^-1）， with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin （HE） staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA （dsDNA） levels were detected by using PicoGreen. The protein expression of cGAS， STING， and nuclear factor-κB （NF-κB） p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ （cTNⅠ）， cardiac troponin T （cTNT）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the peripheral blood were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham group， the model group showed a significantly increased myocardial no-reflow area （P<0.01）. Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01） were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged （P<0.01）， and the levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cTNⅠ， cTNT， and dsDNA were significantly elevated （P<0.01）. Western blot results showed that the myocardial protein expressions of cGAS， STING， and NF-κB p65 were upregulated （P<0.01）. ELISA results showed that the inflammatory factors in the serum such as IL-6， IL-1β， and TNF-α were increased （P<0.01）. Compared with the model group， the group of the TYTZP significantly reduced the levels of myocardial enzyme， troponins， and dsDNA （P<0.01， P<0.05）， improved cardiac function and myocardial microcirculation， alleviated histopathological morphology and inflammatory infiltration， inhibited activation of the cGAS/STING pathway， reduced the expression of NF-κB p65 （P<0.01， P<0.05）， and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury， and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.

Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

Objective:To extract and evaluate the relevant evidence to improve the family discharge preparation of premature infants with bronchopulmonary dysplasia, so as to provide evidence-based basis for clinical formulation of scientific and effective discharge plans.Methods:All the evidence on the family discharge readiness of premature infants with bronchopulmonary dysplasia was collected from Chinese and English databases or websites, and the quality of various studies was evaluated. JBI′s evidence grading and recommendation level system (2014 edition) was used to extract and summarize the evidence.Results:A total of 21 articles were included, and 24 pieces of evidence were summarized, which were divided into seven themes: pre-discharge planning, environmental preparedness, parent education and training, support systems, feeding and nutrition, respiratory management, and discharge follow-up.Conclusions:For preterm infants with bronchopulmonary dysplasia, discharge readiness should be improved in terms of standardizing discharge criteria and implementing a discharge plan; improving family care preparation to ensure discharge support; strengthening health management and implementing a personalized plan; and continuing high-quality follow-up to ensure long-term health.

Objective:To explore the dynamic change trajectory and influencing factors of postoperative fatigue (POF) in patients with early digestive tract cancer undergoing endoscopic submucosal dissection (ESD), so as to provide theoretical basis for individualized management of such patients.Methods:Using cross-sectional survey and convenient sampling method, the patients who underwent ESD for early cancer of digestive tract in the endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to June 2024 were selected as the research objects. The questionnaires were conducted at 30 min, 24 h, 3 days, 5 days, 7 days after ESD with Christensen's postoperative fatigue score. Spearman test was used to analyze the correlation between pain, insomnia and POF. The latent variable growth model was used to identify the potential categories of POF trajectory, and the influencing factors were analyzed by Logistic regression.Results:A total of 232 patients were finally induded, with ages of 19-94(59.53 ± 13.29) years, including 120 males and 112 femalss. The POF level of patients with early cancer of digestive tract showed a downward trend one week after operation. Three postoperative fatigue trajectories were fitted, 9.05% in moderate or severe fatigue low-speed smooth descent group (C1 group); 32.76% in moderate fatigue first decreased quickly and then slowly group (C2 group) and 58.19% in mild fatigue continuous decline group (C3 group). The result of Logistic regression analysis showed that, compared with C1 group, people without religious beliefs were morelikely to enter C2 group [ β = 1.572, OR = 4.818(1.033 - 22.465), P<0.05]; compared with C3 group, patients with high pain level and severe insomnia degree were likely to enter C1 [ β = 2.621, 0.663, OR were 13.754(2.692 - 70.283) and 1.942(1.429 - 2.638), both P<0.05] and C2 [ β = 2.010, 0.491, OR were 7.464(1.890 - 29.482) and 1.634(1.348 - 1.982), both P<0.05] group. Conclusions:There were three potential types of POF in patients with early digestive tract cancer ESD. Medical staff should pay attention to patients with severe insomnia, intense pain and religious beliefs, and give staged fatigue assessment and individualized intervention, so as to reduce the level of POF and promote rapid recovery.

Objective To investigate the effects of varying pulse intervals in the programmed intermittent epidural bolus(PIEB)mode on labor analgesia in primiparous and multiparous women,and to evaluate the differ-ences in analgesic outcomes between these two groups.Methods A total of 60 primiparous and 60 multiparous women who met the inclusion criteria were recruited and randomly allocated into two groups:a 45-minute pulse interval group(P45 group,n=30)and a 60-minute pulse interval group(P60 group,n=30).Epidural labor anal-gesia was initiated when cervical dilation reached 1～3 cm.The programmed intermittent epidural bolus(PIEB)mode was started 45 minutes after analgesia commencement in the P45 group and 60 minutes after analgesia com-mencement in the P60 group.Each pulse delivered 10 ml of a solution containing 0.08%ropivacaine and 0.5 μg/ml sufentanil.Pain scores were assessed using the Visual Analog Scale(VAS)at five specific time points:baseline(t0),1 hour post-analgesia initiation(t1),2 hours post-analgesia initiation(t2),full cervical dilation(t3),and delivery(t4).Secondary outcomes included Bromage scores,the number of patient-controlled analgesia(PCA)button presses,total drug consumption,and adverse reactions.Results In primiparous women,the VAS score at t1 was significantly lower in the P45 group compared to the P60 group(P<0.05),whereas no significant differences were observed in VAS scores between the two groups at t2—t4.The median PCA press count was also significantly lower in the P45 group than in the P60 group(P<0.05).However,there were no significant differences between the groups in terms of total drug consumption,Bromage scores,or the incidence of adverse events(P>0.05).In multiparous women,no significant differences were found in VAS scores,Bromage scores,or PCA press counts between the P45 and P60 groups at any time point(P>0.05).Conversely,total drug consumption was significantly higher in the P45 group compared to the P60 group(P<0.05).Conclusions For primiparous women,a 45-minute pulse interval in the PIEB mode not only provides superior labor analgesia but also significantly reduces the frequency of PCA presses without escalating the risk or severity of motor block or adverse events.For multiparous women,the pulse interval does not substantially influence the effectiveness of labor analgesia.These findings contribute valuable new evidence for refining clinical labor analgesia protocols.

Objective To investigate the impacts of long non coding RNA(LncRNA)-PH domain containing 5 antisense RNA 1(FGD5-AS1)on the proliferation,migration,and invasion of colorectal cancer(CRC)cells by regulating the miR-299-5p/recombinant lysine specific demethylase 4B(KDM4B)axis.Methods The expressions of LncRNA FGD5-AS1,miR-299-5p,and KDM4B were detected by qRT-PCR in the surgically resected CRC tissues and adjacent tissues of 34 CRC patients CRC cells HCT116 were separated into si-NC group,si-FGD5-AS1 group,si-FGD5-AS1+inhibitor NC group,and si-FGD5-AS1+miR-299-5p inhibitor group.The levels of mRNA in each group were detected.CCK8,scratch assay,and Transwell assay were ap[plied to detect the proliferation,migration,and invasion of HCT116 cells in each group.Western blot was applied to detect the expression of proteins.Dual luciferase reporter gene assay verified the interaction mechanism between LncRNA FGD5-AS1 and miR-299-5p,and between miR-299-5p and KDM4B.Results LncRNA FGD5-AS1 and KDM4B were highly expressed in CRC tissue,while miR-299-5p was low expressed in CRC tissue(P＜0.05).The expression of LncRNA FGD5-AS1 mRNA,KDM4B mRNA,OD450,scratch healing rate,invasion number,PCNA,MMP-2,MMP-9,KDM4B in the si-FGD5-AS1 group were lower than those in the si-NC group,the expression of miR-299-5p mRNA was higher than that in the si-NC group(P＜0.05).Compared with the si-FGD5-AS1 group and si-FGD5-AS1+inhibitor NC group,the expression of miR-299-5p in the si-FGD5-AS1+miR-299-5p inhibitor group decreased(P＜0.05),the KDM4B mRNA,OD450,scratch healing rate,number of invasions,and expression of PCNA,MMP-2,MMP-9,KDM4B increased(P＜0.05).LncRNA FGD5-AS1 targeted negative regulation of miR-299-5p,while miR-299-5p targeted negative regulation of KDM4B.Conclusion Knocking down LncRNA FGD5-AS1 may inhibit the proliferation,migration,and invasion of CRC cells,and its mechanism may be achieved by regulating the miR-299-5p/KDM4B signaling axis.

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Purpose: Cancer has become a significant major public health concern, making the discovery of new cancer markers or therapeutic targets exceptionally important. Elevated expression of tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) expression has been observed in certain types of cancer. This project aims to investigate the function of TNFRSF12A in tumors and the underlying mechanisms. Materials and Methods: Various websites were utilized for conducting the bioinformatics analysis. Tumor cell lines with stable knockdown or overexpression of TNFRSF12A were established for cell phenotyping experiments and subcutaneous tumorigenesis in BALB/c mice. RNA-seq was employed to investigate the mechanism of TNFRSF12A. Results: TNFRSF12A was upregulated in the majority of cancers and associated with a poor prognosis. Knockdown TNFRSF12A hindered the colorectal cancer progression, while overexpression facilitated malignancy both in vitro and in vivo. TNFRSF12A overexpression led to increased nuclear factor кB (NF-κB) signaling and significant upregulation of baculoviral IAP repeat containing 3 (BIRC3), a transcription target of the NF-κB member RELA, and it was experimentally confirmed to be a critical downstream factor of TNFRSF12A. Therefore, we speculated the existence of a TNFRSF12A/RELA/BIRC3 regulatory axis in colorectal cancer. Conclusion TNFRSF12A is upregulated in various cancer types and associated with a poor prognosis. In colorectal cancer, elevated TNFRSF12A expression promotes tumor growth, potentially through the TNFRSF12A/RELA/BIRC3 regulatory axis.