OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors（SGLT-2i） in patients with heart failure with preserved ejection fraction（HFpEF） in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics， comorbidities， and differences in drug treatment were compared between the two groups. Based on univariate analysis， multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF， followed by further stratified analysis. RESULTS Among 358 HFpEF patients， the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR＝9.063，95%CI（4.924-16.679） ] ， atrial fibrillation [OR＝3.135，95%CI（1.590-6.178） ] ， coronary artery heart disease [OR＝1.888，95%CI（1.072-3.327） ] and the use of loop diuretics [OR＝3.822， 95%CI （1.588-9.200） ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF （ P ＜0.05）. The results of the stratified descriptive analysis were consistent with those of the multivariate analysis， showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM，atrial fibrillation， coronary artery heart disease， and those receiving loop diuretics （ P ＜0.05）； whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function （ P ＞0.05）. CONCLUSIONS In the real-world clinical practice， the utilization of SGLT-2i in patients with HFpEF remains suboptimal， and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes， atrial fibrillation， coronary artery heart disease， and the use of loop diuretics.

Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

The incidence and mortality of colorectal cancer （CRC） in China have been on a steady rise. Current therapeutic approaches can curb the progression of CRC to a certain extent， but issues such as toxic side effects， high metastasis rate， and high recurrence rate cannot be ignored. In recent years， alkaloid components derived from traditional Chinese medicine （TCM） have demonstrated tremendous potential in the prevention and treatment of CRC due to their diverse structures， complex mechanisms， and broad biological activities. Representative alkaloids such as matrine， berberine and evodiamine exert anti-CRC effects through multiple pathways： regulating signaling pathways including Wnt/β-catenin， nuclear factor-κB， signal transducer and activator of transcription 3， and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin； inhibiting the proliferation， migration， and invasion of CRC cells； inducing cell apoptosis and autophagy； arresting the cell cycle progression； regulating the gut microbiota； suppressing cellular glycolysis； and inducing ferroptosis.

Objective:To compare the effect of empirical cefazolin and vancomycin on the adverse outcomes in peritoneal dialysis (PD)-associated peritonitis patients.Methods:This was a retrospective analysis of a single-centre prospective cohort. Clinical data of consecutive PD-related peritonitis episodes occurring for the first time in patients (≥18 years) between January 1, 2008 and December 31, 2021 were reviewed. Patients were classified into a cefazolin group or a vancomycin group according to the empirical antibiotic regimen. The primary endpoint was peritonitis-related death within 1 month of onset and the secondary endpoint was transfer to haemodialysis for peritonitis-related reasons within the same period. Differences in both endpoints between the two regimens were analysed in the overall population and in the Gram-positive peritonitis subgroup. Univariable and multivariable logistic regression models were used to estimate the risk of adverse outcomes associated with antibiotic choice. Propensity-score matching was performed to control for confounding bias.Results:A total of 516 eligible PD patients developed peritonitis during the study period were included, among whom 138 received empirical cefazolin and 322 received vancomycin. Baseline characteristics were significantly different between the cefazolin and vancomycin groups, including annual income >50 000 yuan ( χ2=17.854, P<0.001), cardiovascular disease history ( χ2=3.909, P=0.048), prior peritonitis history ( χ2=18.327, P<0.001), serum albumin ( t=2.430, P=0.013), triglycerides ( Z=-3.108, P=0.002), total cholesterol ( t=3.752, P<0.001), phosphate ( t=3.362, P=0.002) and sodium ( t=3.021, P=0.004). Neither peritonitis-related mortality nor transfer to haemodialysis differed between the cefazolin and vancomycin groups in the overall cohort or in the Gram-positive peritonitis subgroup (all P>0.05). Logistic regression analysis (univariable and multivariable) showed that empirical vancomycin was not associated with a higher risk of adverse outcome when compared with cefazolin in the overall cohort or in the Gram-positive peritonitis subgroup (all P>0.05). After propensity-score matching, results remained consistent (all P>0.05). Conclusion:Empirical cefazolin and vancomycin yield similar rates of short-term adverse outcomes in patients with PD-associated peritonitis, including those caused by Gram-positive organisms.

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

Objective:To observe the effect of acupuncture-synchronized exercise training on the learning and memory of rats after middle cerebral artery occlusion (MCAO), and to explore its mechanism.Methods:Among sixty 8-week-old SPF-grade Sprague-Dawley male rats, 6 were randomly chosen to form a sham group, and the rest received MCAO. After successful modeling, 18 rats were assigned at random to either the model, asynchronous or synchronous group, each of 6. The asynchronous group received 20 minutes of acupuncture followed by 20 minutes of treadmill training, while the synchronous group received the acupuncture during their treadmill training. There was no special intervention for the sham and model groups. There were 5 sessions/week for 21 days. Neurological deficit in the rats was assessed using Longa scoring 24h after the modeling and after the 21 days. The localization navigation test was performed on days 17-20 of the experiment, and the latency to escape was recorded. A space exploration experiment was performed the next day, and rats were tested for dwell time and the number of transits of the original platform quadrant. After the intervention, the morphology of hippocampal tissue was observed using HE staining. The mitochondria of the rats′ hippocampal neurons were observed using transmission electron microscopy. MDA and SOD levels were recorded. And the protein expression levels of the Parkin, PINK1, LC3-II/ LC3-Ⅰ, P62 and Beclin-1 genes were detected using western blotting.Results:The model group showed significantly higher average Longa scores than the sham group, with less time spent in the target quadrant and fewer crossings of the platform quadrant. The HE staining revealed numerous degenerating neurons, and swollen mitochondria with vacuolization and sparse cristae. There was also a significant decrease in Parkin, PINK1, LC3-II/LC3-I and Beclin-1 expression and in SOD. But there was a significant increase in P62 expression and MDA, on average. Compared with the model group, both the non-synchronous and synchronous groups showed significantly lower average Longa scores, with more time spent in the target quadrant and more platform crossings. Their neuron morphology was close to normal, with more intact cristae and autophagic bodies in the mitochondria. Those groups showed greater Parkin, PINK1, LC3-II/LC3-I and Beclin-1 expression and had higher SOD levels, on average, with significantly lower P62 expression and less MDA. But compared with the non-synchronous group, the synchronous group spent more time in the target quadrant and had significantly more platform crossings. LC3-II/LC3-I and Beclin-1 expression were higher, on average, as were SOD levels. P62 expression and MDA levels were significantly lower.Conclusions:Acupuncture synchronized with exercise improves the learning and memory of rates after MCAO. The mechanism may be related to reducing oxidative stress levels and activating mitochondrial autophagy.

Objective:To translate and adapt the postoperative recovery in children (PRiC) scale, developing a Chinese version for children undergoing dental treatment under general anesthesia (PRiC-DTGA) with validated psychometric properties.Methods:The PRiC scale underwent forward-backward translation using Brislin′s model. A convenience sample of DTGA patients from the Department of Anesthesiology, School of Stomatology, The Fourth Mility Force Medical University was enrolled for a cross-sectional survey on postoperative complications. Delphi expert consultation informed cultural adaptation based on survey findings to develop the PRiC-DTGA Chinese version. Psychometric validation included reliability and validity testing in a separate DTGA cohort at the same center (April-October 2024).Results:Results from the cross-sectionalsurvey of 231 children showed that 82.7% (191/231) of them hadat least one postoperative complication within 72 hours, and these complications were mainly mild local symptoms. Additionally, 358 copies of the Chinese version of the PRiC-DTGA scale were distributed; 21 invalid questionnaires with incomplete information were excluded, and a total of 337 cases were included inthe study. The final PRiC-DTGA comprised 22 items across three dimensions including physical comfort, social ability, and negative emotional. Exploratory factor analysis (EFA) confirmed all factor loadings>0.4. Confirmatory factor analysis (CFA) demonstrated adequate fit: χ 2/df=1.665, tucker-Lewis index (TLI)=0.924, comparative fit index (CFI)=0.896, standardized root mean square residual (SRMR)=0.041, and root mean square error of approximation (RMSEA)=0.044 (90% CI: 0.035-0.053). Reliability was strong with Cronbach′s α (total scale)=0.853, subscale α=0.632-0.723, split-half reliability=0.824. Validity indices met standards: scale-content validity index (S-CVI)=0.909, Item-CVI range=0.944-1.000, average variance extracted (AVE)=0.473-0.501, composite reliability (CR)=0.830-0.913. Conclusions:The systematically adapted PRiC-DTGA demonstrates robust reliability and validity, serving as an effective tool for assessing postoperative recovery quality in Chinese children following DTGA.