ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

Diabetic cognitive impairment （DCI） has an insidious onset and progressive and irreversible development. There is currently no first-line treatment for DCI. Early intervention of diabetes with traditional Chinese medicine （TCM） can effectively control blood sugar and improve cognitive impairment， which has significant advantages. As a representative of bitter and cold heat-clearing medicines， Coptidis Rhizoma， known for its abilities to clear heat and dampness and remove turbidity and toxins， has been widely used in the clinical prevention and treatment of diabetes， Alzheimer's disease， vascular dementia， and other cognitive impairments. This article systematically summarized relevant literature and observed that Coptidis Rhizoma has shown good potential in the prevention and treatment of DCI with its active ingredients such as berberine and quercetin， drug pairs such as Coptidis Rhizoma-Scutellariae Radix， Coptidis Rhizoma-Acorus Tatarinowii Rhizoma， Coptidis Rhizoma-Pinelliae Rhizoma， Coptidis Rhizoma-Zingiberis Rhizoma， and prescriptions such as Gegen Qinliantang， Huanglian Jiedutang， Banxia Xiexintang， Huanglian Wendantang， Jiaotai Wan， Danggui liuhuangtang， and related Chinese patent medicines. Its mechanism may be related to regulating glucose metabolism， improving insulin resistance， improving amyloid β-protein （Aβ） deposition and tau protein phosphorylation， inhibiting neuroinflammation and oxidative stress， and regulating the "microbe-gut-brain axis". The article systematically reviewed the research progress of Coptidis Rhizoma and its prescriptions in the prevention and treatment of DCI， aiming to preliminarily explain the scientific connotation of Coptidis Rhizoma and provide a basis for its clinical application in the prevention and treatment of DCI.

This paper reviews the published articles of recent years on the application of deep learning methods in automatic localization of acupoint, and summarizes it from 3 key links, i.e. the dataset construction, the neural network model design, and the accuracy evaluation of acupoint localization. The significant progress has been obtained in the field of deep learning for acupoint localization, but the scale of acupoint detection needs to be expanded and the precision, the generalization ability, and the real-time performance of the model be advanced. The future research should focus on the support of standardized datasets, and the integration of 3D modeling and multimodal data fusion, so as to increase the accuracy and strengthen the personalization of acupoint localization.
Deep Learning ; Acupuncture Points ; Humans ; Neural Networks, Computer

Objective To observe the effect of Shoutai Pills on endometrial decidualization of mice with recurrent spontaneous abortion(RSA);To explore its possible mechanism in the treatment of RSA based on histone modification.Methods Totally 40 female CBA/J mice were divided into normal group,model group,Shoutai Pills low-dosage group(7.5 g/kg),Shoutai Pills high-dosage group(15 g/kg)and dydrogesterone group(3 mg/kg).The normal group were co housed with BALB/C male mice,while the other groups were co housed with DBA/2 male mice to establish an RSA mouse model.After modeling,the administration groups were given corresponding medication solution by gavage,while the normal group and model group were given equal volume of pure water by gavage for 10 consecutive days.The embryo condition was observed and the embryo loss rate was calculated,ELISA was used to detect serum prolactin(PRL)content,HE staining was used to observe the morphological changes of decidual tissue,RT-PCR was used to detect PRL mRNA expression in decidual tissue,Western blot was used to detect the protein expressions of H4ac,H3K27ac,H3K27me3.Results Compared with the normal group,the model group mice showed a significant increase in embryo loss rate,a significant decrease in serum PRL content,disordered arrangement of decidual cells,and extensive bleeding and necrosis;the expression of PRL mRNA and protein in decidual tissue significantly decreased,the protein expressions of H4ac and H3K27ac significantly decreased,while the expression of H3K27me3 protein significantly increased,with statistical significance(P<0.05).Compared with the model group,the embryo loss rate of Shoutai Pills low-and high-dosage groups and the dexamethasone group significantly decreased,the serum PRL content significantly increased,tightly arranged decidual cells,reduced necrosis,and intact glands;the expression of PRL mRNA and protein in decidual tissue of mice in Shoutai Pills high-dosage group and the dexamethasone group significantly increased,the protein expressions of H4ac and H3K27ac significantly increased,the expression of H3K27me3 protein significantly decreased,with statistical significance(P<0.05).Conclusion Shoutai Pills can promote endometrial decidualization in RSA mice,which is related to the changes of histone modification in endometrial stromal cells.

Pan-immune inflammation value (PIV) is a comprehensive immune inflammatory biomarker based on complete blood cell counts, which has been proven to predict treatment response and survival outcomes for different types of tumors. However, the predictive value of the PIV varies in different strategies for tumor treatment. This paper aims to systematically review the latest progress of PIV in predicting survival outcomes and tumor prognosis for immunotherapy, radiotherapy, targeted therapy, endocrine therapy, surgical treatment and neoadjuvant therapy, and analyze its existing challenges and issues, as well as look forward to its future development direction and application prospects.

Objective To investigate the correlation between pre-treatment pan-immune inflammation value (PIV) and clinicopathological features in esophageal squamous cell carcinoma (ESCC) patients with postoperative adjuvant radiotherapy and evaluate its value in prognosis assessment combined with T stage. Methods A retrospective analysis was conducted on data of 85 ESCC patients with postoperative adjuvant radiotherapy in the Department of Radiation Oncology of the Affiliated Hospital of Yangzhou University from January 2019 to January 2023. The receiver operating characteristic (ROC) curve was drew to obtain the optimal cut-off value of PIV and other immune-inflammatory biomarkers. The area under the curve (AUC) and clinical applicability of PIV and other immune-inflammatory biomarkers were compared based on the ROC curve and decision curve analysis (DCA). According to the optimal cut-off value, patients were divided into high PIV group and low PIV group, and the correlation between PIV level and clinicopathological features of ESCC was evaluated. Kaplan-Meier method was used for survival analysis, the Cox proportional hazards model was used for multivariate analysis, and a risk stratification model combining PIV and T stage was established by recursive partitioning analysis (RPA). Results The optimal cut-off value of pre-treatment PIV was determined as 187.22 based on the ROC curve. The AUC of PIV was 0.679, which was greater than 0.640, 0.583, 0.656 and 0.644 of the other four immune-inflammatory biomarkers such as the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR). The 85 patients were divided into low PIV group (< 187.22, n=48) and high PIV group (≥187.22, n=37). The level of PIV was significantly correlated with tumor diameter (P < 0.05). The 3-year overall survival (OS) (75.6% versus 30.6%, P < 0.001) and 3-year disease-free survival (DFS) (56.1% versus 21.0%, P < 0.001) were significantly higher in the low PIV group than the high PIV group. Tumor diameter, T stage and PIV were independent factors affecting OS in ESCC patients (P < 0.05), and T stage and PIV were independent factors affecting DFS in ESCC patients (P < 0.05). A new staging system with three risk groups was established by the RPA stratification model based on T stage and PIV, which further improved the predictive value of prognosis compared with T stage or PIV alone. Conclusion Pre-treatment PIV is helpful in predicting the prognosis of ESCC patients with postoperative adjuvant radiotherapy, and the combination of PIV and T stage can improve the predictive value.

Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

ObjectiveTo investigate the effect of direct-acting antiviral (DAA) on the recurrence of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after curative treatment. MethodsPubMed, Web of Science, Cochrane Library, CNKI, CBM, Wanfang Data, and VIP were searched for the clinical studies of DAA and the recurrence of HCV-related HCC published up to April 2020. Stata 14.0 software was used to perform the meta-analysis. The Cochran Q test was used to evaluate heterogeneity between studies; the fixed effects model was used for non-heterogeneous data, and the random effects model was used for heterogeneous data. The Egger regression method or the Begg rank correlation method was used to evaluate the presence or absence of publication bias. ResultsA total of 10 articles (11 studies) were included in our study, among which 8 articles (9 studies) compared the effect of DAA versus the absence of anti-HCV therapy on the recurrence of HCC after curative treatment. There were 991 patients in DAA group and 808 patients in untreated group. The results of the meta-analysis showed that DAA reduced the recurrence rate of HCC after curative treatment in patients with HCV infection (hazard ratio ［HR］=0.42, 95% confidence interval ［CI］: 0.28?0.36, P＜0.001). Three articles compared the effect of DAA versus interferon for the treatment of hepatitis C on the recurrence of HCC after curative treatment, with 267 patients in DAA group and 212 in interferon group, and the results of the meta-analysis showed that DAA and interferon had a similar effect on the recurrence rate of HCV-related HCC (HR=0.85, 95% CI: 0.64-1.15, P=0.298). ConclusionBoth interferon and DAA can significantly reduce the recurrence risk of HCV-related HCC after curative treatment, with no significant difference between them.

Obesity and binge drinking often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. In this mini-review, we briefly summarize clinical evidence of the synergistical effect of obesity and heavy drinking on steatohepatitis and discuss the underlying mechanisms obtained from the study of several mouse models. High-fat diet (HFD) feeding and binge ethanol synergistically induced steatohepatitis and fibrosis in mice with significant intrahepatic neutrophil infiltration; such HFD-plus-ethanol treatment markedly up-regulated the hepatic expression of many chemokines with the highest fold (approximately 30-fold) induction of chemokine (C-X-C motif) ligand 1 (Cxcl1), which contributes to hepatic neutrophil infiltration and liver injury. Furthermore, HFD feeding activated peroxisome proliferator-activated receptor gamma that subsequently inhibited CXCL1 upregulation in hepatocytes, thereby forming a negative feedback loop to prevent neutrophil overaction; whereas binge ethanol blocked this loop and then exacerbated CXCL1 elevation, neutrophil infiltration, and liver injury. Interestingly, inflamed mouse hepatocytes attracted neutrophils less effectively than inflamed human hepatocytes due to the lower induction of CXCL1 and the lack of the interleukin (IL)-8 gene in the mouse genome, which may be one of the reasons for difficulty in development of mouse models of alcoholic steatohepatitis and nonalcoholic steatohepatitis (NASH). Hepatic overexpression of Cxcl1 and/or IL-8 promoted steatosis-to-NASH progression in HFD-fed mice by inducing neutrophil infiltration, oxidative stress, hepatocyte death, fibrosis, and p38 mitogen-activated protein kinase activation. Collectively, obesity and binge drinking synergistically promote steatohepatitis via the induction of CXCL1 and subsequent hepatic neutrophil infiltration.