GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy.

The expansion of GGC repeats within NOTCH2NLC leads to the translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). This study aims to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy (CAA)-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analyzed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use, and MRI features between NIID patients with and without CMBs. We further performed hematoxylin and eosin (H&E), Perl's, Congo red, and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes, and approximately 20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs suffered a higher incidence of previous ischemic and hemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. H&E staining showed blood vessel leakage and hemosiderin-laden macrophage clusters, and Prussian blue staining revealed brain tissue iron deposition. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labeled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a novel perspective, providing initial clinical, neuroimaging, and pathological evidence suggesting that uN2CpolyG may contribute to a distinct type of CAA.

Epidemiological survey of adult female stress urinary incontinence.

BACKGROUND: The prevalence of stress urinary incontinence (SUI) in adult female in Taiyuan and what are the related risk factors are not clear. The aim of this study was to provide a basis for exploring the prevention and treatment of SUI in adult female in Taiyuan. METHODS: A voluntary online questionnaire was used to investigate adult female in the community and surrounding townships of Taiyuan. Most of the questionnaires refer to the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms, and adapt to the specific circumstances of the region. Data were analyzed using SPSS software (version 22.0). RESULTS: A total of 4004 eligible questionnaires were obtained. The prevalence of SUI in adult female in Taiyuan was 33.5%. Univariate analysis and multivariate logistic regression analysis showed that place of residence, smoking, body mass index, diet, number of deliveries, mode of delivery, dystocia, menopause, oral contraceptives, urinary tract infection, making the bladder empty faster by pushing down and holding urine were risk factors for adult female stress urinary incontinence in Taiyuan. CONCLUSION: The prevalence of SUI in adult female in Taiyuan was high, and based on risk factors identified in this survey, population-level intervention strategies should be developed for the prevention and treatment of adult female SUI in Taiyuan.

Label-free detection of miRNA cancer markers based on terminal deoxynucleotidyl transferase-induced copper nanoclusters.

The variations in microRNA (miRNA) expression levels can be useful biomarkers for the diagnosis of different cancers. In this work, a label-free and sensitive fluorescent method for detection of miRNA-21 is described based on duplex-specific nuclease (DSN) assist target recycling and terminal deoxynucleotidyl transferase (TdT) induced copper nanoclusters (CuNCs). In the absence of target, the 3'-phosphorylated probe DNA cannot be hydrolyzed by DSN and extended by TdT, and failed to synthesizing fluorescent CuNCs. However, the target miRNA-21 can caused the digestion of probe DNA with DSN, releasing primer DNA with 3'-OH. After that, the primer DNA can forms long poly T with the assistance of TdT, leading to synthesize high fluorescent CuNCs. The fluorescence change of CuNCs can be used to identify the concentration of target miRNA-21. Under optimal experimental conditions, this strategy could quantitatively detect miRNA-21 down to 18.7 pM. We have also demonstrated the practical application of our proposed method for monitoring miRNA-21 expression levels in cancer cells. Moreover, this method show good specificity for miRNA-21 detection due to the strong preference of DSN for cutting perfectly matched DNA/RNA duplex, which holds great potential for highly specific quantification of biomarkers in bioanalysis and clinical diagnosis.

Association of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism with the Risk of Atherosclerosis.

AIMS: The objective of this study was to perform a meta-analysis to evaluate the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and susceptibility to atherosclerosis (AS). METHODS: MEDLINE, EMBASE, and the ISI Web of Science were searched for all eligible published studies concerning the relationship of ACE gene polymorphism with AS without language restrictions. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate this relationship under different genetic models using meta-analytic methods. RESULTS: A total of 15 articles (16 studies) were involved in this meta-analysis. The D allele of the ACE gene had a nonsignificant increase in the risk of AS (D versus I: OR = 1.23, 95% CI, .98-1.53, P = .07; I2 = 87.2%, Pheterogeneity < .01). Compared with the II genotype, the DI (relative risk [RR]: 1.35, 95% CI: 1.09, 1.67, P < .01; I2 = 47.8%, Pheterogeneity = .017) and (DD + DI) (RR = 1.38, 95% CI: 1.04, 1.82, P = .02; I2 = 73.3%, Pheterogeneity < .01) genotype of ACE was associated with higher risk of AS, respectively. Subjects with the DD genotype showed a statistically nonsignificant trend toward greater risk of AS (RR = 1.53, 95% CI: .97, 2.43, P = .07; I2 = 88.6%, Pheterogeneity < .01). Further subgroup analyses showed that significant relationships were only found in Europeans under different gene polymorphism or different genotype models rather than Asians. CONCLUSIONS: The present meta-analysis indicated that the D allele in the ACE gene was associated with the risk of AS, especially in Europeans. Furthermore, increased copy number of D allele was significantly associated with increased AS risk in a dose-dependent manner.

A Novel Vaccine Targeting Glypican-3 as a Treatment for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response. Here, in C57/B6 mice, we demonstrated that intravenous infusion of GPC3-coupled lymphocytes (LC/GPC3+) elicited robust GPC3-specific antibody and CTL responses, which effectively restricted proliferation and lysed cultured-HCC cells. Treatment with LC/GPC3+ induced durable tumor regression in HCC-bearing C57/B6 mice. Administration of LC/GPC3+ induced elevated levels of the cytotoxic T cell bioactive factors tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), granzyme B, and perforin, and substantially increased the number of infiltrating CD8+ T cells in tumor tissues. Moreover, immune responses elicited by LC/GPC3+ selectively suppressed GPC3+ tumors, but didn't affect the GPC3- tumors in BALB/c mice. Our findings provide the first preclinical evidence that intravenous infusion of the LC/GPC3+ complex can induce a strong anti-HCC effect through regulating systemic and local immune responses. These results indicate that the LC/GPC3+ complex could be developed as precision therapeutics for HCC patients in the future.

Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn.

Remifentanil-induced hyperalgesia (RIH) is known to be associated with oxidative stress and inflammation. Betulinic acid (BA) was reported to reduce visceral pain owing to its anti-oxidative and anti-inflammatory potential. Here, we -explored whether BA can attenuate RIH through inhibiting oxidative stress and inflammation in spinal dorsal horn. Sprague-Dawley rats were randomly divided into 4 groups: Control, Incision, RIH, and RIH pre-treated with BA. After pretreated with BA (25 mg/kg, i.g.) for 7 days, rats were subcutaneously infused with remifentanil (40 µg/kg) for 30 min during right plantar incision surgery to induce RIH. The paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), spinal oxidative stress and inflammatory mediators were determined. Intraoperative remifentanil infusion induced postoperative hyperalgesia, as evidenced by the significant decrease in PWMT and PWTL (p < 0.01), and the significant increase in oxidative stress and inflammation evidenced by up-regulations of malondialdehyde, 3-nitrotyrosine, interleukin-1ß and tumour necrosis factor-α (p < 0.01) in spinal dorsal horn and matrix metalloproteinase-9 (MMP-9) activity (p < 0.01) in dorsal root ganglion, as well as a decrease in manganese superoxide -dismutase activity (p < 0.01) compared with control and -incision groups. All these results mentioned above were markedly reversed by pre-treatment with BA (p < 0.01) compared with RIH group. These findings demonstrated that BA can effectively attenuate RIH, which associates with potentially inhibiting oxidative stress and subsequently down-regulating MMP-9-related pro-inflammatory cyokines in spinal dorsal horn.

MicroRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells.

Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potential target for cancer therapy. However, many cancer cells are resistant to TRAIL-induced apoptosis and its mechanism is not well understood. In this study, to identify potential therapeutic targets for TRAIL-resistant cancer cells, we compared the expression levels of interferon-stimulated gene 15 in TRAIL-sensitive and TRAIL-resistant hepatocellular carcinoma cell lines. Western blot analysis showed that interferon-stimulated gene 15 expression levels were significantly higher in resistant HLCZ01and Huh7 cells than in sensitive LH86 and SMMC-7721 cells. Interferon-stimulated gene 15 knockdown in resistance cells led to TRAIL sensitivity. Conversely, interferon-stimulated gene 15 overexpression in sensitive cells resulted in TRAIL resistance. Our bioinformatics search detected a putative target sequence for microRNA miR-138 in the 3' untranslated region of the interferon-stimulated gene 15. Real-time quantitative polymerase chain reaction analysis demonstrated that miR-138 was significantly downregulated in TRAIL-resistant cells compared to TRAIL-sensitive cells. Forced expression of miR-138 in resistant cells decreased both messenger RNA and protein levels of interferon-stimulated gene 15, and when exposed to TRAIL, activated poly(adenosine diphosphate-ribose) polymerase, indicating sensitization to TRAIL. The results suggested that miR-138 regulates the interferon-stimulated gene 15 expression by directly targeting the 3' untranslated region of interferon-stimulated gene 15 and modulates the sensitivity to TRAIL-induced apoptosis. MiR-138 may be a target for therapeutic intervention in TRAIL-based drug treatments of resistant hepatocellular carcinoma or could be a biomarker to select patients who may benefit from the treatment.

Interferon-α and cyclooxygenase-2 inhibitor cooperatively mediates TRAIL-induced apoptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Interferon-alpha (IFN-α) has recently been recognized to harbor therapeutic potential in the prevention and treatment of HCC, but it remains controversial as to whether IFN-α exerts direct cytotoxicity against HCC. Cyclooxygenase-2 (COX-2) is overexpressed in HCC and is considered to play a role in hepatocarcinogenesis. Therefore, we aimed to elucidate the combined effect of a COX-2 inhibitor, celecoxib, and IFN-α on in vitro growth suppression of HCC using the hepatoma cell line HLCZ01 and the in vivo nude mouse xenotransplantation model using HLCZ01 cells. Treatment with celecoxib and IFN-α synergistically inhibited cell proliferation in a dose- and time-dependent manner. Apoptosis was identified by 4׳,6-diamidino-2-phenylindole dihydrochloride and fluorescent staining. IFN-α upregulated the expression of TRAIL, while celecoxib increased the expression of TRAIL receptors. The combined regimen with celecoxib and IFN-α reduced the growth of xenotransplanted HCCs in nude mice. The regulation of IFN-α- and COX-2 inhibitor-induced cell death is impaired in a subset of TRAIL-resistant cells. The molecular mechanisms of HCC cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. Interferon-α and the COX-2 inhibitor celecoxib synergistically increased TRAIL-induced apoptosis in hepatocellular carcinoma. These data suggest that IFN-α and celecoxib may offer a novel role with important implications in designing new therapeutics for TRAIL-resistant tumors.

Epithelial cell-related prognostic risk model in breast cancer based on single-cell and bulk RNA sequencing.

Objective: This study aims to construct an epithelial cell-related prognostic risk model for breast cancer (BRCA) and explore its significance. Methods: GSE42568, GSE10780, GSE245601, and TCGA-BRCA datasets were sourced from public databases. Epithelial cell-related differentially expressed genes were identified using single-cell data analysis. Venn diagrams determined the intersecting genes between epithelial cell-related and BRCA-related genes. Batch Kaplan-Meier (K-M) survival analysis identified core intersecting genes for BRCA overall survival. Consensus clustering, enrichment, LASSO, and COX regression analyses were performed on the core intersecting genes, and then a prognostic risk model was constructed. The diagnostic and prognostic effectiveness of the risk model was subsequently evaluated and immune infiltration analysis was conducted. Finally, qRT-PCR was used to verify the expression of genes in the risk model. Results: There were 374 intersecting genes between epithelial cell-related and BRCA-related genes, among which 51 core intersecting genes were associated with BRCA prognosis. Consensus clustering categorized TCGA-BRCA into C1 and C2, with shared regulation of the estrogen signaling pathway. Three genes (DIRC3, SLC6A2, TUBA3D) were independent predictors of BRCA prognosis, forming the basis for a risk model. Except for exhibiting satisfactory diagnostic efficacy, the risk score elevation correlated with poor prognosis, elevated matrix, immune, and ESTIMATE scores, and negative correlation with microsatellite instability. The in vitro results confirmed the differential expression levels of DIRC3, SLC6A2, and TUBA3D. Conclusion: The prognostic risk model associated with epithelial cells demonstrates effective diagnostic performance in BRCA, serving as an independent prognostic factor for BRCA patients. Additionally, it exhibits a correlation with immune scores.

Bioequivalence of Blonanserin Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects.

Blonanserin is a novel oral antischizophrenic drug. Under fasting (n = 50) and fed (n = 60) conditions, this study compared the bioequivalence of the generic blonanserin tablet with the reference blonanserin tablet. In this single-center, randomized, open-label, 2-period, 2-sequence, crossover study, 110 patients were randomly given a 4-mg dose of either the test or reference blonanserin tablet with a 14-day washout period. Blood samples were taken before performing and up to 72 hours following. A validated high-performance liquid chromatography-tandem mass spectrometry technique was used to measure the levels of blonanserin in plasma. Safety was evaluated throughout the study. The study found no significant differences in the maximum observed drug concentration in the plasma (Cmax ), the area under the plasma concentration-time curve from time 0 to the last sampling time (AUC0-t ), and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) between the 2 blonanserin formulations. The 90% confidence intervals of the geometric mean ratio of the test/reference formulations for Cmax , AUC0-t , and AUC0-∞ were within the 80%-125% limit. Food dramatically raised blonanserin exposure, and also significantly prolonged the lag time of absorption. No serious adverse events occurred. These results indicate that the 2 blonanserin formulations were bioequivalent and well tolerated in healthy Chinese subjects. In clinical treatment, it is necessary to consider the food effect of blonanserin.

The effect of acupuncture on oxidative stress in animal models of vascular dementia: a systematic review and meta-analysis.

BACKGROUND: Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD. METHOD: Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software. RESULTS: In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes. CONCLUSION: Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: This study was registered in PROSPERO (CRD42023411720).

Research status and trends of physical activity on depression or anxiety: a bibliometric analysis.

Background: Anxiety and depression are prevalent mental disorders. As modern society continues to face mounting pressures, the incidence of anxiety and depression is on the rise. In recent years, there has been an increasing breadth of research exploring the relationship between anxiety, depression, and physical activity (PA). However, the current research progress and future development trends are unclear. The purpose of this study is to explore the research hotspots and development trends in this field, and to provide guidance for future studies and to provide some reference for clinicians. Methods: We searched the relevant literature of Web of Science Core Collection from the establishment of the database to August 15, 2023. CiteSpace, VOSviewer and Bibliometrix Packages based on the R language were used to analyze the number of publications, countries, institutions, journals, authors, references, and keywords. Results: A total of 1,591 studies were included in the analysis, and the research in the field of PA on anxiety or depression has consistently expanded. The USA (304 publications), Harvard University (93 publications), and the journal of affective disorders (97 publications) were the countries, institutions, and journals that published the highest number of articles, respectively. According to the keywords, students and pregnant women, adult neurogenesis, and Tai Chi were the groups of concern, physiological and pathological mechanisms, and the type of PA of interest, respectively. Conclusion: The study of PA on anxiety or depression is experiencing ongoing expansion. Clinicians can consider advising patients to take mind-body exercise to improve mood. In addition, future researchers can explore the mind-body exercise and its impact on anxiety or depression, PA and anxiety or depression in specific populations, and adult neurogenesis of various exercise in anxiety or depression.

Value of neutrophil-to-lymphocyte ratio in neuronal intranuclear inclusion disease.

Background and objectives: The neutrophil-to-lymphocyte ratio (NLR) is a widely recognized marker of inflammation in peripheral blood. However, its specific role in neuronal intranuclear inclusion disease (NIID) has not been reported. This study aims to investigate the relationship between NIID and NLR. Methods: A multicenter database was collected, including 157 NIID patients from seven hospitals (The Affiliated Hospital of Xuzhou Medical University, Yantai Yuhuangding Hospital, Tengzhou Central People's Hospital,The Affiliated Brain Hospital of Nanjing Medical University, Liaocheng People's Hospital,The Second Hospital of Shandong University, Inner Mongolia People's Hospital, Xuanwu Hospital Capital Medical University,The First Affiliated Hospital of USTC), along with 157 age- and gender-matched healthy control subjects. White blood cell counts (including neutrophils, lymphocytes, monocytes, eosinophils, and basophils) were obtained, and the NLR was calculated. Additionally, cognitive impairment was assessed using clinical evaluation scores. Results: NIID patients exhibited significantly higher NLR values compared to the healthy control group (p < 0.001). The plasma NLR levels in NIID patients showed a weak positive correlation with disease duration (r = 0.219, p = 0.016). However, no significant correlations were found between NLR and age of onset or cognitive impairment (p > 0.05). Conclusion: There is a significant association between NLR and NIID, suggesting a potential role of peripheral blood inflammation in the pathogenesis of NIID.

Supplements for cognitive ability in patients with mild cognitive impairment or Alzheimer's disease: a protocol for systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).

Efficacy and safety of acupuncture for postpartum hypogalactia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postpartum hypogalactia (PH) is prominent during lactation and may negatively impact the mother's or infant's health. Acupuncture is widely used to increase maternal breast milk production. However, the effects of acupuncture on PH remain unclear. Therefore, this review aimed to evaluate the efficacy and safety of acupuncture in individuals with PH. MATERIALS AND METHODS: Articles on potentially eligible randomized controlled trials (RCTs) on acupuncture for PH published from database inception to October 2023 were retrieved from the PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, WanFang, and VIP databases. Two reviewers independently screened the records, extracted essential information, and evaluated the methodological quality of the RCTs using the revised Cochrane risk-of-bias (RoB) tool. The primary outcome was a change in serum prolactin (PRL) levels before and after treatment. Secondary outcomes included milk secretion volume (MSV), total effective rate (TER), mammary fullness degree (MFD), and exclusive breastfeeding rate (EBR). Meta-analyses were performed using RevMan v5.4. Finally, the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. RESULTS: This study included 19 RCTs involving 2,400 participants. The included studies were classified as having an unclear to high RoB. Our findings indicated that, overall, acupuncture showed a significant effect in increasing serum PRL levels (standardized mean differences [SMDs] = 1.09, 95% confidence interval [CI]: 0.50, 1.68), MSV (SMD = 1.69, 95% CI: 0.53, 2.86), TER (relative risk [RR] = 1.25, 95% CI: 1.10, 1.42), and EBR (RR = 2.01, 95% CI: 1.07, 3.78) compared to that in the control group; however, no difference in MFD (SMD = 1.17, 95% CI: -0.09, 2.42) was observed. In the subgroup analysis, acupuncture combined with Chinese herbs or conventional treatment was significantly more effective in increasing serum PRL levels, MSV, and TER than did Chinese herbs or conventional treatment alone. Moreover, acupuncture alone resulted in significantly higher serum PRL levels compared to Chinese herbs; however, this benefit was not observed for TER and MFD. The quality of evidence was critically low. CONCLUSION: Acupuncture may effectively increase milk secretion in women with PH. However, owing to the low quality of evidence, further rigorously designed studies are warranted to confirm our findings.

Non-pharmacological interventions for behavioral and psychological symptoms of dementia: A systematic review and network meta-analysis protocol.

Introduction: Dementia patients often experience behavioral and psychological symptoms (BPSD), which severely affect their quality of life and activities of daily living. Non-pharmacological interventions are effective in treating BPSD, according to multiple clinical trials and systematic reviews. However, the optimal non-pharmacological treatment remains controversial. Therefore, the study aims to evaluate and compare multiple non-pharmacological methods for treating BPSD in order to identify the optimal non-pharmacological intervention. Objective: This study aims to perform a systematic review and network meta-analysis of evidence on non-pharmacological interventions in the treatment of BPSD, which may potentially guide future research and clinical decisions. Methods: In order to select potentially relevant randomized controlled trials (RCTs), 10 academic databases and 3 clinical trial registries will be systematically searched from inception until the 1 October 2022. Two researchers will independently extract information from eligible articles. The primary outcome is the severity of BPSD. Herein, Pairwise and Bayesian network meta-analyses will be conducted utilizing STATA 15.0 and ADDIS 1.16.8. Evidence quality will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Results from this study will be published in peer-reviewed journals or conference reports. Discussion: In this study, we aim to comparatively assess the efficacy of various non-pharmacological treatments for BPSD. Findings from this review will help clinicians to make evidence-based treatment decisions. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022352095].

[Effect of AT1 receptor on changes of tyrosine hydroxylase-immunoreactivity in rostral ventrolateral medulla induced by brain cholinergic stimuli in rats].

OBJECTIVE: To investigate the effect of AT1 receptor on the changes of tyrosine hydroxylase-immunoreactivity (TH-IR) in rostral ventrolateral medulla (RVLM) induced by brain cholinergic stimuli in rats. METHODS: Male SD rats were randomly divided into 4 groups: NS + CBC group, Los + CBC group, Los + NS group and NS + NS group. AT1 was blocked by pretreatment of 20 µg losartan in Los + CBC and Los + NS groups; intracerebroventricular injection of 0.5 µg carbachol was used for cholinergic stimuli in NS + CBC and Los + CBC groups; normal saline (NS) was used for control. The output amount of natrium in kidney, glomerular filtration rate (GFR) and renal plasma flow (PRF) were observed. The changes of TH-IR in the RVLM were observed by immunohistochemistry. RESULT: In NS + CBC group carbachol induced potent natriuresis, after pretreatment of losartan the natriuretic effect was partially inhibited in Los + CBC group. Both the number and optical density of TH-IR positive neurons in NS + CBC group were markedly increased than those in NS + NS group (P < 0.05); while those in Los + CBC group were significantly lower than those in NS+CBC group (P < 0.05). Intracerebroventricular injection of carbachol and losartan had no effect on GFR and RPF(P > 0.05). CONCLUSION: The results suggest that cholinergic stimuli can induce potent natriuresis and increase the activity of adrenergic neurons in the RVLM; the above effects can be down regulated by blockade of brain AT1 receptor.

[Activation of mitochondrial aldehyde dehydrogenase 2 and inhibition of mitochondrial permeability transition pore involved in cardioprotection of ethanol postconditioning].

OBJECTIVE: To investigate whether activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and inhibition of mitochondrial permeability transition pore (mitoPTP) were involved in the cardioprotection of ethanol postconditioning in isolated rat heart. METHODS: Hearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 min of regional ischemia (occlusion of left anterior descending artery) followed by 120 min of reperfusion. The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) release during reperfusion were measured. Infarct size was measured by TTC staining method and the expression of ALDH2 at mRNA level of left anterior myocardium was detected by RT-PCR. RESULT: In contrast to ischemia and reperfusion, ethanol postconditioning improved the recovery of left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure during reperfusion, reduced LDH release and infarct size. The expression of ALDH2 mRNA level was increased. Administration of mitoPTP activator atractyloside attenuated the effect of ethanol postconditioning, LDH release and infarct size were increased, and the recovery of hemodynamic parameters was inhibited. The expression of ALDH2 mRNA was decreased. CONCLUSION: Ethanol postconditioning has cardioprotection effect, which may be associated with upregulating mitochondrial ALDH2 mRNA expression and inhibiting the opening of mitochondrial permeability transition pore.

[Hemodynamics and aortic tension induced by two septic shock models in rats].

OBJECTIVE: To compare the ventricular-dynamic parameters and thoracic aorta tension induced by two septic shock models in rats. METHODS: Septic shock models were induced by cecal ligation or puncture (CLP) and intraperitoneal injection of lipopolysaccharide (LPS) in rats. The carotid artery was cannulated and connected to a pressure transducer to determine mean arterial blood pressure (MABP). Ventricular dynamic parameters, including heart rate (HR), left ventricular developed pressure (LVDP) and maximal rise/fall velocity of ventricular pressure (± dP/dtmax) were determined. Isolated thoracic rings were mounted on an organ bath and the tension of the vessel was recorded. RESULT: The mortality was 65.2% in CLP shock rats, but no death in LPS shock rats. The MABP and HR of CLP rats were decreased more prominently than those of LPS rats (P < 0.01). Contraction induced by high K(+) (60 mmol/L) or 10⁻6 mol/L phenylephrine (PE) in endothelium-intact and endothelium-denuded aortic rings was all attenuated, but in LPS rats it was more prominent (P < 0.01). CONCLUSION: Two rat septic shock models can decrease ventricular-dynamic parameters and vasoconstriction responsiveness of aorta. The ventricular-dynamic parameters decrease more prominently in CLP model, while vasoconstriction responsiveness of aorta changes more in LPS model.

[Betulinic acid ameliorates impairment of endothelium-dependent relaxation induced by oxidative stress in rat aorta].

OBJECTIVE: To investigate the effect of betulinic acid (BA) on relaxation in isolated rat aortic rings and its antioxidant property on oxidative stress of blood vessels. METHODS: Aortic rings were isolated and BA was cumulatively added into organ bath. Isometric tension of endothelium intact or endothelium denuded thoracic aortic rings previously contracted by phenylephrine (PE) was recorded. Then aortic rings were randomly divided into normal control group, BA control group, H(2)O(2) group and BA+H(2)O(2) group, after being previously contracted by PE, isometric tension of endothelium-dependent relaxation induced by Ach was recorded. RESULT: Exposure of intact endothelium rings previously contracted by PE to BA at the concentrations of 10(-7) mol/L-10(-4) mol/L evoked a significant concentration dependent relaxation, which was inhibited by pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME, 10(-4)mol/L), but not by indometacin (10(-5)mol/L). The pD2 value of BA was 5.24 ± 0.04, and the EC(50)value was 2.45 x 10(-6)mol/L. Exposure of endothelium denuded rings previously contracted by PE to BA did not affect the relaxation in isolated aortic rings. ACh induced a dose-dependent relaxation that was weakened by pretreatment with H(2)O(2) (5 10(-4) mol/L) for 15 min. The EC(50) of BA markedly attenuated the inhibition of relaxation induced by H(2)O(2). CONCLUSION: BA can evoke a concentration-dependent relaxation in aortic rings previously contracted by PE, which may be mediated by NO. And the decrease of endothelium-dependent relaxation in rat aortic rings exposed to H(2)O(2) can be markedly attenuated by BA, which may be mediated by reducing oxidative stress and maintaining the activity of NO in aortic rings.