The Impact of Harvesting Mechanization on Oolong Tea Quality.

Mechanization is the inevitable future of tea harvesting, but its impact on tea chemistry and quality remains uncertain. Our study examines untargeted metabolomic data from 185 oolong tea products (Tieguanyin) made from leaves harvested by hand or machine based on UPLC-QToF-MS analysis. The data revealed a minimum 50% loss for over half of the chemicals in the machine-harvested group, including catechins, theaflavin, gallic acid, chlorogenic acid, and kaempferol-3-gluocside. Integrating sensory evaluation, OPLS-DA identified the six most important metabolites as significant contributors to sensory decline caused by harvesting mechanization. Furthermore, our research validates the possibility of using DD-SIMCA modelling with untargeted metabolomic data for distinguishing handpicked from machine-harvested tea products. The model was able to achieve 93% accuracy. This study provides crucial insights into the chemical and sensory shifts during mechanization, along with tools to manage and monitor these changes.

Experimental and Theoretical Insights into the Effect of Dioldibenzoate Isomers on the Performance of Polypropylene Catalysts.

Experimental investigations and density functional theory (DFT) calculations were carried out to study the comprehensive effect of different 3,5-heptanedioldibenzoate (HDDB) optical isomers as the internal electron donor on the catalytic performance of Ziegler-Natta catalysts. The experimental catalytic activity of HDDB has a positive correlation with the relative content of the mesomer incorporated during catalyst preparation, while the hydrogen response of HDDB displayed a negative correlation with the relative content of the mesomer. In order to apply the DFT calculation results to the macroscopic activity of the catalyst, the content of the active centers of the catalyst was analyzed. Assuming that the content of the active centers is proportional to the internal electron donor content of the catalyst, binary linear regression was carried out, which showed a good linear correlation between experimental activity data and internal electron donor content. Furthermore, the fitted activity of the single active centers aligned well with the calculated activation energies. These results revealed that the catalytic activity of polypropylene (PP) catalysts is dependent on both the active center content and the catalytic activity of an individual active center. Additionally, the lower hydrogen response of HDDB leads to a higher molecular weight of polypropylene obtained from the RS-containing catalyst compared to the SS-containing catalyst. Further study reveals that the hydrogen transfer reactions of 2,4-pentanediol dibenzoate (PDDB)/HDDB are influenced by the orientation of the methyl/ethyl groups in different isomers, which affect the activation energy differences between the hydrogen transfer reaction and the propylene insertion reaction, and finally influence the molecular weight of PP.

Decreased FGF23 inhibits placental angiogenesis via the ERK1/2-EGR-1 signaling pathway in preeclampsia.

PURPOSE: This study aimed to investigate the expression of fibroblast growth factor 23 (FGF23) in pregnant women with preeclampsia and elucidate its role in promoting placental angiogenesis through the ERK1/2-EGR-1 signaling pathway. METHODS: Serum FGF23 levels were measured by ELISA in healthy pregnant women and patients with preeclampsia during the first, second, and third trimesters of pregnancy. Wound healing, Transwell, and tube formation assays were performed to investigate the effects of FGF23 on cell migration, invasion and tube formation. The expression of vascular endothelial growth factor A (VEGF-A) and its upstream signaling molecules, p-ERK, and EGR-1, in placental tissues was detected by RT-qPCR and western blotting. Additionally, the effect of FGF23 on VEGF-A, p-ERK, and EGR-1 expression was further explored in vitro. RESULTS: Serum FGF23 levels increased with gestational age. During the third trimester, the control group exhibited a more pronounced increase in FGF23 levels than the preeclampsia group. Administering exogenous FGF23 promoted trophoblast cell migration, invasion and enhanced tube formation in vascular endothelial cells. The expression levels of VEGF-A, p-ERK, and EGR-1 in the placental tissues were significantly lower in the preeclampsia group than in the control group. In vitro experiments confirmed that FGF23 up-regulated VEGF-A expression through the p-ERK/EGR-1 signaling pathway. CONCLUSION: The serum level of FGF23 decreased in pregnant women with preeclampsia, inhibiting the ERK1/2-EGR-1 pathway and resulting in decreased expression of VEGF-A, thereby inhibiting placental angiogenesis. This could be a potential mechanism involved in the progression of preeclampsia.

Cardiovascular diseases consequences of type 1, type 2 diabetes mellitus and glycemic traits: A Mendelian randomization study.

OBJECTIVE: This Mendelian randomization (MR) study aimed to investigate the relationships between type 1 diabetes (T1D), type 2 diabetes (T2D), and glycemic traits, including fasting insulin, fasting glucose, and HbA1c, with cardiovascular diseases (CVDs). METHODS: We selected genetic instruments for predisposition to T1D, T2D, fasting insulin, fasting glucose, and HbA1c based on published genome-wide association studies. Using a 2-Sample MR approach, we assessed associations with 12 common CVDs sourced from the FinnGen and UK Biobank studies, along with stroke subtypes obtained from the GIGASTROKE and MEGASTROKE Consortium. RESULTS: T1D was associated with SVS. T2D showed associations with AIS, LAA, CES, SVS, coronary heart disease, myocardial infarction, pulmonary embolism, DVT of lower extremities, peripheral vascular diseases. Genetically predicted higher HbA1c levels were associated with eight CVDs. The results of MVMR aligned with the primary findings for T1D and T2D. CONCLUSIONS: T1D and T2D exhibit different genetic predisposition to CVDs. BMI, LDL, and HDL play intermediary roles in connecting TID and T2D to specific types of CVDs, providing insights into the potential underlying pathways and mechanisms involved in these relationships. Strategies aimed at achieving sustained reductions in HbA1c levels may offer potential for reducing the risk of various CVDs.

The occurrence, progression and development of four types of gastric mucosal atrophic lesions and their histopathological characteristics.

OBJECTIVE: To investigate the occurrence and development of gastric mucosal atrophic lesions and their histopathological characteristics. METHODS: Histopathological diagnosis and immunohistochemical staining using the EnVision two-step method were conducted on 1969 gastric mucosal atrophic lesions obtained from gastroscopic biopsy specimens. A total of 48-month three-stage endoscopic biopsy follow-ups were performed. RESULTS: When the gastric mucosal epithelium was affected by infection, chemical irritation, or immune or genetic factors, the gastric mucosal epithelium glands atrophied, the mucosa became thinner, the number of glands decreased, the intestinal epithelium progressed to metaplasia and smooth muscle fibre became hyperplasia. Such changes may lead to the proliferation and dysplasia of epithelial cells of the gastric mucosa and neoplastic hyperplasia in nature; this is referred to as gastric mucosal atrophic lesions in this study. According to this definition, the present study divided gastric mucosal atrophy into four types: (1) glandular atrophy of the lamina propria; (2) compensatory proliferative atrophy; (3) intestinal metaplasia atrophy; and (4) smooth muscle proliferative atrophy. The incidence rates of the above were 40.1% (789/1969), 14.3% (281/1969), 27.8% (547/1969) and 17.9% (352/1969), respectively. One- to 4-year follow-ups found that the changes were not significant and that the percentages of patients with disease exacerbation were 85.7% (1688/1969) and 9.8% (192/1969). The percentages of patients who developed low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia were 2.8% (55/1969) and 1.1% (21/1969), respectively; 0.7% (13/1969) of patients developed intramucosal cancer. CONCLUSION: Gastric mucosal atrophic lesions and histopathological staging are based on the morphological characteristics of gastric mucosal atrophy and the hypothesis of malignant transformation of cells during the occurrence and development of mucosal atrophy. Mastering pathological staging is beneficial to clinicians for enacting precise treatment and is important for reducing the incidence of gastric cancer.

Impact of Bivalirudin on Patients with Acute Coronary Syndrome Undergoing Rotational Atherectomy in Real-Life Setting: A Retrospective Cohort Study.

BACKGROUND: No evidence exists on the impact of bivalirudin in patients with the acute coronary syndrome undergoing rotational atherectomy. This study aimed to evaluate the impact of bivalirudin on patients with acute coronary syndrome undergoing rotational atherectomy. METHODS: This was a retrospective cohort study conducted in our hospital between January 2017 and December 2019. The study included patients with acute coronary syndrome undergoing rotational atherectomy. Furthermore, 2 cohorts were included in this study (bivalirudin cohort and control cohort unfractionated heparin). The primary end-point was in-hospital net adverse clinical events. The secondary endpoint was all-cause mortality at 23 months. RESULTS: The study included 157 patients with 33 (21.0%) in the bivalirudin cohort and 124 (79.0%) in the control cohort. Net adverse clinical events during hospitalization in the bivalirudin cohort were higher than that in the control cohort [9 (27.3%) vs. 14 (11.3%), P = .021]. However, there was no significant difference in all-cause mortality at 23 months between the 2 cohorts [25 (20.2%) vs. 10 (30.3%), P =.214]. After adjusting for potential confounders, the usage of bivalirudin was not associated with net adverse clinical event (odds ratio = 0.90; 95% CI: 0.18-4.45; P =.890), and the hazard ratio for all-cause mortality at 23 months was 1.01 (95% CI: 0.33-3.15; P =.983). CONCLUSION: Bivalirudin appears to exhibit a similar impact as unfractionated heparin on patients with acute coronary syndrome undergoing rotational atherectomy in real-life setting.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis.

OBJECTIVE: To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades. METHODS: This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references. RESULTS: A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76). CONCLUSION: The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

Optical coherence tomography angiography for the characterisation of retinal microvasculature alterations in pregnant patients with anaemia: a nested case‒control study.

AIMS: To characterise retinal microvascular alterations in the eyes of pregnant patients with anaemia (PA) and to compare the alterations with those in healthy controls (HC) using optical coherence tomography angiography (OCTA). METHODS: This nested case‒control study included singleton PA and HC from the Eye Health in Pregnancy Study. Fovea avascular zone (FAZ) metrics, perfusion density (PD) in the superficial capillary plexus, deep capillary plexus and flow deficit (FD) density in the choriocapillaris (CC) were quantified using FIJI software. Linear regressions were conducted to evaluate the differences in OCTA metrics between PA and HC. Subgroup analyses were performed based on comparisons between PA diagnosed in the early or late trimester and HC. RESULTS: In total, 99 eyes of 99 PA and 184 eyes of 184 HC were analysed. PA had a significantly reduced FAZ perimeter (ß coefficient=-0.310, p<0.001), area (ß coefficient=-0.121, p=0.001) and increased circularity (ß coefficient=0.037, p<0.001) compared with HC. Furthermore, higher PD in the central (ß coefficient=0.327, p=0.001) and outer (ß coefficient=0.349, p=0.007) regions were observed in PA. PA diagnosed in the first trimester had more extensive central FD (ß coefficient=4.199, p=0.003) in the CC, indicating impaired perfusion in the CC. CONCLUSION: It was found that anaemia during pregnancy was associated with macular microvascular abnormalities, which differed in PA as pregnancy progressed. The results suggest that quantitative OCTA metrics may be useful for risk evaluation before clinical diagnosis. TRIAL REGISTRATION NUMBERS: 2021KYPJ098 and ChiCTR2100049850.

The Application of Public Art Design Based on Digital Technology in Urban Landscape Environmental Monitoring.

Public art (PA) is a powerful tool for enhancing the environment in public spaces since it not only relieves the oppression caused by urban architecture but also enhances and beautifies urban public spaces. As DT (digital technology) develops so quickly nowadays, it offers PA significant technological assistance to achieve new functions, and changes in modern people's aesthetic preferences and psychological makeup also present new demands for PA. This essay explores the use of PA design in the creation of urban landscapes from the viewpoint of DT. In order to do this, this paper suggests a method for measuring the environmental impact of urban landscapes that combines landscape measurement and semantic assessment. Full-connection algorithm and greedy algorithm are introduced to identify urban functional types with high-dimensional characteristics for the boundary tree classification model of high-dimensional feature classification. The findings indicate that the public service area's producer and user accuracy are, respectively, 0.8783 and 0.7833. It offers a fresh concept for the identification of urban functional zones while solving the issues of low identification efficiency and poor accuracy.

The Histopathological Types and Distribution Characteristics of Gastric Mixed Tumors.

Objective: The present study aimed to investigate the histopathological types and distribution characteristics of gastric mixed tumors. Methods: Detailed histological observations, together with related immunohistochemical and genetic tests, were analyzed on 960 surgically resected samples in 6 hospitals with gastric mixed tumors from May 2017 to May 2021 in this retrospective study. Results: Epithelial-derived tumors accounted for 80.10% (769/960) of the gastric mixed tumor samples studied, and tumors of different tissue origins accounting for 10.83% (104/960), mesenchymal-derived tumors accounting for 6.25% (60/960), neuroendocrine tumors accounting for 2.40% (23/960), and lymphoma accounting for 0.42% (4/960). The histological types of gastric mixed tumors identified as most commonly were epithelial originated, followed by mixed tumors of different tissue originated, then mixed neuroendocrine, lymphoma, and mesenchymal originated in sequence. The histological number of gastric mixed tumors was ≤ 3 in 83.23% (799/960) of cases and > 4 in 16.77% (161/960) of cases. The mixed histological patterns of gastric mixed tumors were divided into three types: those with tumor cells interspersed with each other, those with incomplete fibrous tissue separation, and those without fibrous tissue separation. The gene target characteristics of gastric mixed tumors were the existence of multi-gene mutation, including human epidermalgrowth factor receptor-2 (HER2) gene amplification, key result areas (K-ras) and platelet-derived growth factor receptor alpha (PDGFRA). Conclusion: Gastric mixed tumors should be adequately sampled, each piece of tissue should be involved in the morphological proportional division of the tumor, and any independent histological component should be written into the pathological examination report.

[Effect of acupuncture on hypothalamic functional connectivity in patients with premature ova-rian insufficiency based on resting-state functional magnetic resonance imaging].

OBJECTIVE: To compare the differences in functional connectivity(FC) between the hypothalamus and whole brain regions in patients with premature ovarian insufficiency (POI) and healthy volunteers based on resting-state functional magnetic resonance imaging (rs-fMRI) and investigate the mechanism of acupuncture on treatment of POI. METHODS: Twelve POI patients were recruited to the acupuncture group and 12 healthy volunteers to the control group. Patients in the acupuncture group received acupuncture at two groups of acupoints alternatively, including Baihui (GV20), Zhongwan (CV12), Shenting (GV24), Shenshu (BL23), Ciliao（BL32） and so on, 30 min once time, 3 times per week for 12 weeks. The state of patients was evaluated by modified Kupperman Index (KI) and self-rating anxiety scale (SAS). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-mullerian hormone (AMH) were tested by microparticle-based chemiluminescence. B ultrasonography was used to detect the antral follicle count (AFC). Meanwhile, POI patients and healthy volunteers underwent the rs-fMRI examination before and after acupuncture treatment and after enrollment, respectively. With hypothalamus as the region of interest, the differences in FC between the hypothalamus and other brain regions in POI patients and healthy volunteers and the changes of FC between the hypothalamus and whole brain regions in POI patients before and after acupuncture were observed. RESULTS: The SAS and KI scores of pre-treatment POI patients were higher than those in the control group （P<0.01）.In compa-rison with those pre-treatment, FSH, LH, and SAS and KI scores of POI patients decreased after treatment, while AFC increased (P<0.05). Compared with the control group, the FC of the left hypothalamus with left central sulcus, right middle occipital gyrus, and left paracentral lobule increased, but decreased with left globus pallidus of the lenticular nucleus in POI patients. Furthermore, the FC of the right hypothalamus with the left hippocampus, the left para-central lobule, and the right central sulcus increased, while the FC between the right hypothalamus and the right superior frontal gyrus decreased (P<0.05). For the acupuncture group, compared with the conditions before treatment, the FC of the right hypothalamus with the left inferior frontal gyrus, the left insula, and right inferior frontal gyrus was strengthened, but weakened with the left gyrus rectus (P<0.05). CONCLUSION: The abnormal FC between the hypothalamus and whole brain regions may be one of the central pathological factors of POI. Acupuncture can improve the ovarian function and clinical symptoms of patients with POI, which may be related to its effect in regulating the FC between the hypothalamus and multiple brain regions.

How Does Helicobacter pylori Infection Cause Gastric Mucosal Atrophy.

Objective: To investigate the occurrence and development of gastric mucosal atrophy due to Helicobacter pylori (Hp) infection and the accompanying histomorphological features. Methods: Detailed histological observations and immunohistochemical examinations were conducted via 197 endoscopic biopsies and endoscopic submucosal dissection specimens of gastric mucosal atrophic lesions with gastric Hp infection. Detailed observation was made of columnar cells in the proliferative region of the deep gastric pit and the isthmus of the gastric gland, as well as the upper part of the glandular cervix. Results: The infection of the gastric mucosa by Hp firstly led to the proliferative disorder of stem cells in the normal proliferative region of the gastric mucosa. This caused substantial propagation of cells in the proliferative region of the deep gastric pit and the isthmus of the gastric gland, as well as the upper part of the glandular cervix, as a means to replenish the damaged surface mucus cells. However, the propagation of stem cells in the proliferative region was insufficient for downward migration, and the normal physiological process of differentiation into fundic/pyloric gland cells was disrupted, resulting in glandular atrophy of the intrinsic layer of the gastric mucosa. Persistent Hp infection and disruption of stem cell proliferation in the proliferative region subsequently resulted in extensive segmental hyperplasia of the gastric mucosa and glandular atrophy of the lamina propria. Conclusion: The occurrence, development, and histomorphological features of gastric mucosal atrophy due to gastric Hp infection provide a reliable pathological basis for precise treatment by clinicians and are of great significance for controlling the development of gastric cancer.

Research on the Histological Features and Pathological Types of Gastric Adenocarcinoma With Mucinous Differentiation.

Objective: To discuss the histological features, pathological types, and prognosis of gastric adenocarcinoma with mucinous differentiation. Methods: Specimens of 189 cases of gastric adenocarcinoma with mucinous differentiation were collected for detailed histomorphology, immunohistochemistry, fluorescence in situ hybridization, and follow-up. Results: In accordance with the morphological and histological structural features of the cancer cells as well as the area ratio of the mucus, gastric adenocarcinoma with mucinous differentiation was divided into four types, namely pure mucinous carcinoma, intraductal papillary mucinous carcinoma, signet ring cell type mucinous carcinoma, and mixed cell type mucinous carcinoma. Based on the macroscopic types according to Bormann's classification, pure mucinous carcinoma was mostly Type I, intraductal papillary mucinous carcinoma was mostly Type II, signet ring cell type mucinous carcinoma was mostly Type IV, and mixed cell type mucinous carcinoma was mostly Type III. The 5-year survival rate was 69.2, 64.2, 0, and 31.5%, respectively. There was a statistical difference in the lymph node metastasis rate and survival rate of the four carcinoma types. The invasion features of pure mucinous carcinoma entailed penetrating corrosively in a push-in form, without blood vessel or lymphatic metastasis and with few lymphocytes and lymphatic nodules in the marginal area. Thus, there was little lymph node metastasis and invasion of nerves. The HER2 protein expression rate was 40.2% (76/189), the HER2 gene amplification detected by FISH technology was 16.9% (32/189). Conclusion: The independent histological type, four subtypes, and histopathological classification of gastric mucinous adenocarcinoma are important for the prognosis evaluation and precise treatment of this disease.

Shaping ability of ProTaper Gold and WaveOne Gold nickel-titanium rotary instruments in simulated S-shaped root canals.

BACKGROUND/PURPOSE: Gold metal technology improves flexibility and the resistance to cyclic fatigue of the endodontic mechanical files. This study compared the performance of ProTaper Gold (PTG) multiple file system and WaveOne Gold (WOG) single file system in simulated S-shaped root canals, which represents one of the most challenging root canal morphology. MATERIALS AND METHODS: Forty S-shaped canals (n = 20 canals/per group) in resin blocks were instrumented to an apical size of 0.25 mm using PTG and WOG Primary, respectively. The total amount of resin removal, canal transportation, centering ratio, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis was performed by using Mann-Whitney U-test (α = .05). RESULTS: None of the files fractured during the instrumentation. The WOG group removed significantly less amount of resin at 0, 3, 6, 7 and 9 mm from the apex (P < .05). The WOG group remained more centered in canals at 0 mm from the apex (P < .05). The PTG group showed a better centering ability and less canal transportation at 4, 5 and 6 mm from the apex (P < .05). In the coronal curvature portion, the use of WOG Primary significantly decreased curvature angle and increased radius compared with PTG instruments (P < .05). There was no significant difference between the two groups in terms of the apical curvature angle and radius change (P > .05). CONCLUSION: The WOG Primary file has a less aggressive dentin cutting and more centered apical preparation. The PTG system is more advantageous in shaping the coronal curvature of S-shaped canal.

Networks Are Associated With Acupuncture Treatment in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: A Resting-State Imaging Study.

Background: Irritable Bowel Syndrome (IBS), as a functional gastrointestinal disorder, is characterized by abdominal pain and distension. Recent studies have shown that acupuncture treatment improves symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) by altering networks in certain brain regions. However, few studies have used resting-state functional magnetic resonance imaging (fMRI) to compare altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment. Objective: To analyze altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment. Methods: A total of 74 patients with IBS-D and 31 healthy controls (HCs) were recruited for this study. fMRI examination was performed in patients with IBS-D before and after acupuncture treatment, but only at baseline in HCs. Data on the left frontoparietal network (LFPN), default mode network (DMN), salience network (SN), ventral attention network (VAN), auditory network (AN), visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and right frontoparietal network (RFPN) were subjected to independent component analysis (ICA). The functional connectivity values of inter-network were explored. Results: Acupuncture decreased irritable bowel syndrome symptom severity score (IBS-SSS) and Hamilton Anxiety Scale (HAMA). It also ameliorated symptoms related to IBS-D. Notably, functional connectivity between AN and VAN, SMN and DMN, RFPN and VAN in IBS-D patients after acupuncture treatment was different from that in HCs. Furthermore, there were differences in functional connectivity between DMN and DAN, DAN and LFPN, DMN and VAN before and after acupuncture treatment. The inter-network changes in DMN-VAN were positively correlated with changes in HAMA, life influence degree, and IBS-SSS in IBS-D. Conclusion: Altered inter-network functional connectivity is involved in several important hubs in large-scale networks. These networks are altered by acupuncture stimulation in patients with IBS-D.

[Mind-regulating and spleen-strengthening needling technique improves abdominal hypersensitivity and emotion by enhancing functional connectivity between hippocampus and brain regions in diarrhea-predominant irritable bowel syndrome patients].

OBJECTIVE: To compare the difference of brain functional connectivity between diarrhea-predominant irritable bowel syndrome (IBS-D) patients and healthy volunteers and changes after acupuncture intervention, so as to investigate the underlying mechanism of acupuncture in regulating functional activities of IBS-D patients by using seed point correlation analysis. METHODS: A total of 25 IBS-D patients and 25 healthy volunteers were recruited in the present study and respectively attributed to acupuncture group and control group. The IBS-D patients received manual acupuncture stimulation of Baihui (GV20), Yintang (EX-HN3), and bilateral Tianshu (ST25), Zusanli (ST36), Shangjuxu (ST37), Sanyinjiao (SP6) and Taichong (LR3) with mind-regulating and spleen-strengthening technique for 30 min, once a day, 3 days a week for 6 weeks. Before and after the intervention, the IBS symptom severity scale (IBS-SSS) was used to assess the patients' state of abdominal pain, distention and defecation, and Hamilton Anxiety Rating Scale (HAMA) employed to evaluate the patients' anxiety severity. The resting state functional magnetic resonance imaging (rs-fMRI) data were acquired and preprocessed by using SPM8 and DPARSE soft-wares. Seeds (bilate-ral hippocampus regions) to whole-brain analysis was performed to obtain the mean time series of the left and right seed regions, followed by making Pearson correlation analysis to obtain the correlation coefficient (time series from each seed region with the rest of the voxels in the brain), and making a multivariate comparative correction to get data of functional connectivity (FC) of bilateral hippocampus regions and to find the related difference in the brain regions. Then, the differences of the FC of brain regions between IBS-D patients and healthy volunteers were compared. RESULTS: Following acupuncture treatment, both the HAMA and IBS-SSS scores were significantly reduced in the acupuncture group compared with its pre-treatment (P<0.01). Compared with the healthy volunteers, there were a reduction in the functional connectivity between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus and left superior gyrus, and between the right hippocampus region and the right fusiform gyrus, left inferior temporal gyrus, left inferior occipital gyrus, left rectus gyrus, left insula, left precuneus, right angular gyrus, left middle occipital gyrus, right precuneus, and the left superior temporal gyrus, and an increase in the FC between the left hippocampus and left superior temporal gyrus was increased in ISB-D patients. Self-comparison showed that after the treatment, the FC was increased between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus, bilateral lingual gyrus, left amygdala, right inferior occipital gyrus, right insula, right middle frontal gyrus, left middle frontal gyrus and the left middle occipital gyrus; and between the right hippocampus seed region and the posterior inferior cerebellar lobe, left inferior temporal gyrus, left suboccipital gyrus, right fusiform gyrus, left insula, right inferior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right middle frontal gyrus, left supplementary motor area and right supplementary motor area, and decreased between the left hippocampus region and the left anterior cingulate, paracingulate gyrus and the right posterior central gyrus in IBS-D patients. CONCLUSION: Mind-regulating and spleen-strengthening acupuncture intervention may improve the abdominal pain and distension and emotional state in IBS-D patients, which is possibly associated with its effect in enhancing FC between the hippocampus and brain regions.

UCHL1 inhibition attenuates cardiac fibrosis via modulation of nuclear factor-κB signaling in fibroblasts.

The ubiquitin-proteasome system (UPS) plays an essential role in cellular homeostasis and myocardial function. Ubiquitin carboxy-terminal hydrolase 1 (UCHL1) is involved in cardiac remodeling, but its underlying mechanisms are largely unknown. Here, we observed that the UCHL1 was significantly up-regulated in angiotensin II-infused heart and primary cardiac fibroblast (CF). Systemic administration of the UCHL1 inhibitor LDN57444 significantly ameliorated cardiac fibrosis and improved cardiac function induced by angiotensin II. Also, LDN57444 inhibited CF cell proliferation as well as attenuated collagen I, and CTGF gene expression in the presence of Ang II. Mechanistically, UCHL1 promotes angiotensin II-induced fibrotic responses by way of activating nuclear factor kappa B (NF-κB) signaling. Moreover, suppression of the NF-κB pathway interfered with UCHL1 overexpression-mediated fibrotic responses. Besides, the chromatin immunoprecipitation assay demonstrated that NF-κB can bind to the UCHL1 promoter and trigger its transcription in cardiac fibroblasts. These findings suggest that UCHL1 positively regulates cardiac fibrosis by modulating NF-κB signaling pathway and identify UCHL1 could be a new treatment strategy for cardiac fibrosis.

Circ-HIPK2 Accelerates Cell Apoptosis and Autophagy in Myocardial Oxidative Injury by Sponging miR-485-5p and Targeting ATG101.

Myocardial injury has been deemed as a major cause of heart diseases including myocarditis and coronary heart disease, which have brought multiple mortalities globally. Long non-coding RNAs (lncRNAs) are widely recognized in diverse diseases. However, the role of circular RNA HIPK2 (circ-HIPK2) remains unclear in myocardial injury induced by H2O2. We attempted to investigate the probable role of circ-HIPK2 in myocardial injury induced by H2O2. This study discovered that the treatment of H2O2 inhibited cell proliferation but boosted cell apoptosis and autophagy. ATG101 was upregulated in primary mouse neonatal cardiomyocytes under H2O2 treatment. ATG101 knockdown promoted proliferation and limited apoptosis by attenuating autophagy in H2O2-injured mouse neonatal cardiomyocytes. Furthermore, miR-485-5p was validated to combine with ATG101 and circ-HIPK2, and circ-HIPK2 positively regulated ATG101 expression by sponging miR-485-5p. At last, silenced circ-HIPK2 mediated the promotion of cell proliferation, and repression of cell apoptosis was restored by ATG101 amplification. In a word, circ-HIPK2 facilitates autophagy to accelerate cell apoptosis and cell death in H2O2-caused myocardial oxidative injury through the miR-485-5p/ATG101 pathway, indicating a novel therapeutic target point for patients with myocardial injury.

[Exploration on the relationship between acupuncture for mind-regulation and flow theory].

Based on the story of Chinese idiom, paodingjieniu (a magical and skilled form of craftsmanship) as the breakthrough point, this paper discusses the both paoding (cook) and the experienced acupuncture practitioner have the same high skills and explores the potential relationship between mind-regulation in treatment with acupuncture and flow theory. It is believed that the skills of ancient acupuncture practitioner in mind-regulation with acupuncture is not only a kind of "Tao" mode, but also a state of "flow". By the discussion on mind-regulation and flow theory, modern people may have more clear recognition on the mind regulation in treatment with acupuncture so as to better determine the therapeutic methods of acupuncture for mind-regulation.

Influence of CYP2C19 genotype on antiplatelet treatment outcomes after percutaneous coronary intervention in patients with coronary heart disease.

The aim of the study was to compare the clinical efficacy and safety of ticagrelor and clopidogrel in patients with coronary heart disease one year after percutaneous coronary intervention (PCI), and to explore their association with the CYP2C19 gene polymorphism. A total of 971 patients with coronary heart disease who were hospitalized and underwent PCI from April 2016 to May 2017 were studied. All 971 patients were divided into three subgroups according to CYP2C19 gene types as fast metabolizing, slow metabolizing and very slow metabolizing type. Patients were also classified according to the oral antiplatelet aggregation drugs they received: clopidogrel group and ticagrelor group. The incidence of major adverse cardiac events (MACE) and bleeding events in the clopidogrel-treated and ticagrelor-treated groups and in patients with fast, slow, and very slow CYP2C19 metabolisms were compared. Binary logistic regression analysis was carried out to analyze the risk factors associated with MACEs and hemorrhagic events. Patients on ticagrelor had a greater number of bleeding complications compared to those on clopidogrel (P<0.001), with no difference in MACE between the two groups (P=0.399). The incidence of MACE was significantly higher in very slow metabolizing patients receiving clopidogrel (P<0.001) while the incidence of bleeding complications was significantly higher in fast metabolizing patients receiving ticagrelor (P<0.001). The regression analysis revealed that the CYP2C19 gene mutation, a dual-antiplatelet therapy, and a stroke history were all significantly associated with MACE. By contrast, a dual-antiplatelet therapy and a stroke history were significantly associated with bleeding events. Findings of the present study indicated that clopidogrel and ticagrelor were equally efficacious post-PCI. Efficacy of clopidogrel was reduced in patients with very slow CYP2C19 genotype while bleeding complications were higher in patients with fast CYP2C19 genotype receiving ticagrelor. CYP2C19 genotyping may be used to provide guidance to optimize individual antiplatelet treatment.