Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9).

Hypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidation, with borneol as the initial raw material, using the strategy of combinatorial molecular chemistry. The structure of the compound was confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry, with a purity of more than 99.5%. The compound 221s (2,9) can significantly reduce the systolic and diastolic blood pressure of SHR rats by about 50 mmHg and 35 mmHg after 4 weeks of administration. The antihypertensive effect of 221s (2,9) is equivalent to that of captopril. The use of 221s (2,9) can reduce the content of Ren, Ang II and ACE in the serum of SHR rats, inhibit the RAAS and enhance the vascular endothelial function by upregulating the level of NO. Pathological studies in this area have shown that high dosage of 221s (2,9) can notably protect myocardial fibrosis in rats and reduce the degeneration and necrosis of myocardial fibers, inflammatory cell infiltration, and proliferation of fibrous tissue in the heart of rat. Therefore, the existing work provided a foundation for preclinical research and follow-up clinical research of 221s (2,9) as a new drug.

Papaverine Infusion Through Aortic Root before Cardiac Self-recovery in Heart Valve Replacement with TiO2 Nanocrystalline Film Material.

This work was to investigate TiO2 nanocrystalline film material in heart valve replacement (HVR) and the effect of papaverine infusion through the aortic root before cardiac self-recovery during the HVR. TiO2 nanocrystalline films were prepared by radio frequency (RF) reactive sputtering. The crystallization characteristics and surface morphology of TiO2 nanocrystalline films were observed by X-ray diffraction and scanning electron microscopy, and the anti-platelet adhesion and anti-coagulation properties of the films were analyzed. 86 patients with heart valve disease were selected and all underwent HVR. They were randomly divided into a control group (routine treatment) and an experimental group (papaverine perfusion through aortic root), with 43 cases in each group. The rate of cardiac self-recovery and the dosage of dopamine were observed. The results showed that the TiO2 nanocrystalline film was composed of a large number of uniform particles, and the average particle size was about 18.97 ± 7.28 nm. The rate of cardiac self-recovery in the experimental group was 97.67%, which was significantly higher than that in the control group (67.44%) (P< 0.05). The dosage of epinephrine, dopamine, and duration of cardiopulmonary bypass (CPB) assistance in the observation group were less than those in the control group (P < 0.05). These results indicated that TiO2 nanocrystalline film could be used in HVR, and papaverine infusion through aortic root before HVR and myocardial protection measures can significantly improve the rate of cardiac self-recovery and promote postoperative recovery.

Giant Atrial Septal Artery Aneurysm with a Fistula to the Right Atrium.

An atrial septal artery aneurysm is a rare disease, especially accompanied with a fistula. During clinical practice, it is very important to clear the anatomical details of the coronary aneurysm before operation. In the current article, we report a giant atrial septal artery aneurysm originating from a branch of the RCA combined with a coronary right atrial fistula. The coronary artery aneurysm should be evaluated using multiple diagnostic and imaging modalities, such as echocardiography, coronary artery angiography, magnetic resonance imaging, and cardiac CT, especially three-dimensional reconstruction, which could help us to distinguish the physiological and anatomical characteristics of the CAA and fistula.

Association of SNP rs1867277 in FOXE1 Gene and Cleft Lip with or without Cleft Palate in a Han Chinese Population.

BACKGROUND: The genetic factors causing cleft lip with or without cleft palate (CL ± P) are still unclear. The SNPs in FOXE1 gene were associated with CL ± P. However, the results have been inconsistent. OBJECTIVE: We explored the associations of four SNPs in FOXE1 gene and CL ± P by a family based study. MATERIALS AND METHODS: 128 children with CL ± P and their parents were recruited. rs3758249 and rs1867277 were genotyped by high-resolution melting curve (HRM) method, whereas rs1443434 and rs907577 were genotyped by Sequenom MassARRAY® method. The software PLINK, FBAT and FAMHAP were used for analyzing data. RESULTS: rs1867277 was associated with CL ± P (Pm = 0.0395). The patients were divided into two subgroups, individuals with cleft lip only and persons with cleft lip and palate. There were no associations in subgroup analyses. CONCLUSION: We confirmed the association of FOXE1 gene and CL ± P by a family based study. For the first time, rs1867277 was significantly associated with CL ± P.

Illness management and recovery program for mental health problems: reducing symptoms and increasing social functioning.

AIMS AND OBJECTIVES: To evaluate the effectiveness of the Illness Management and Recovery Program in comparison with the current standard of care in terms of reduction of symptoms, rehospitalisation rates and social functioning in Asia. BACKGROUND: Focus of treatment for Mental Health had been shifted from mere management of symptoms to that of achievement of recovery. In the recovery process, strategies to achieve higher level of functioning were used (Psychiatric Services 2014, 65, 171). However, two main factors hindered clients from attaining recovery: first, the lack of Mental Health resources in the community and second the negative attitudes of healthcare professionals towards mental illness (American Journal of Psychiatric Rehabilitation 2012, 15, 131). Hence, it is essential to implement an effective programme that will train mental health professionals to use more effective techniques and materials in helping the clients to better integrate into society by achieving skills in their attempt to work towards recovery. DESIGN: This study adopts a time series experimental quantitative design. METHODS: Fifty participants who consented to the study were randomly assigned to two groups. Participants in the experimental group received the experimental management and recovery programme, while the control group received standard care management by the community psychiatric nurses for a period of 12 months. RESULTS: Participants in the experimental group reported significantly lower number of admissions, shorter length of stay, lower Brief Psychiatric Rating Scale scores, and also reported significantly higher scores on both the Illness Management and Recovery Scale and the Global Assessment Scale. CONCLUSION: This study demonstrated the effectiveness of IMR in helping Asian people with mental illness to not only reduce symptoms and hospitalisations but also improve social functioning. They have benefitted from the program although they are living in a different cultural setting from where IMR was developed. RELEVANCE TO CLINICAL PRACTICE: The success of this study has raised the standard of care in the community intervention and led more people to their recovery.

Motivational Interviewing Approach Used by a Community Mental Health Team.

The current study aimed to (a) evaluate the effectiveness of motivational interviewing, as applied by a community mental health team (CMHT) based in Singapore; (b) reduce hospital admissions and length of hospital stay; and (c) improve global functioning and satisfaction of individuals with mental illness. The current study used a quasi-experimental method. A convenience sample of 120 participants was selected from the caseload of the CMHT. Participants received motivational interviewing sessions at least once every month for 1 year. Data on the number of hospital admissions, length of hospitalization, Global Assessment of Functioning, and patient satisfaction were collected at baseline and 6 and 12 months. Participants who underwent the CMHT services with motivational interviewing were more compliant to treatment, resulting in significant reduction in hospitalization and improvement in functionality. Motivational interviewing is effective in facilitating better illness management for patients in the community. Adoption of the motivational interviewing approach may potentially provide significant benefits for psychiatric support services in the community.

Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells.

Non-esterified fatty acids (NEFAs) are pivotal in energy metabolism, yet high concentrations can lead to ketosis, a common metabolic disorder in cattle. Our laboratory observed lower levels of L-histidine in cattle suffering from ketosis, indicating a potential interaction between L-histidine and NEFA metabolism. This relationship prompted us to investigate the metabolomic alterations in bovine mammary epithelial cells (BMECs) induced by elevated NEFA levels and to explore L-histidine's potential mitigating effects. Our untargeted metabolomic analysis revealed 893 and 160 metabolite changes in positive and negative models, respectively, with VIP scores greater than 1 and p-values below 0.05. Notable metabolites like 9,10-epoxy-12-octadecenoic acid were upregulated, while 9-Ethylguanine was downregulated. A pathway analysis suggested disruptions in fatty acid and steroid biosynthesis pathways. Furthermore, L-histidine treatment altered 61 metabolites in the positive model and 34 in the negative model, with implications for similar pathways affected by NEFA. Overlaying differential metabolites from both conditions uncovered a potential key mediator, 1-Linoleoylglycerophosphocholine, which was regulated in opposite directions by NEFA and L-histidine. Our study uncovered that both NEFA L- and histidine metabolomics analyses pinpoint similar lipid biosynthesis pathways, with 1-Linoleoylglycerophosphocholine emerging as a potential key metabolite mediating their interaction, a discovery that may offer insights for therapeutic strategies in metabolic diseases.

Circ_0000006 and circ_0000160 regulate hsa-let-7e-5p/UBQLN4 axis in aortic dissection progression.

Aortic aneurysms (AA) and aorta dissection (AD) are life-threatening conditions with a rising incidence and high mortality rate. Recent research has linked non-coding RNAs to the regulation of AA and AD progression. In this study, we performed circRNA sequencing, microRNA (miRNA) sequencing, and messenger RNA (mRNA) sequencing on plasma samples from AA and AD patients to identify the key circRNA-miRNA-mRNA axis involved in the transition from AA to AD. Our results showed elevated levels of circ_0000006 and circ_0000160, along with decreased levels of hsa-let-7e-5p in AD samples compared to AA samples. Predictive analysis suggested that circ_0000006 and circ_0000160 potentially target hsa-let-7e-5p, which in turn may bind to the mRNA of Ubiquilin 4 (UBQLN4). In an AD cell model using vascular smooth muscle cells (VSMCs), silencing circ_0000006 and circ_0000160 attenuated the effects of platelet-derived growth factor (PDGF)-induced phenotypic changes, proliferation, and migration. This effect was partially reversed by inhibiting hsa-let-7e-5p. Furthermore, we found that overexpression of UBQLN4 counteracted the effects of hsa-let-7e-5p, suggesting UBQLN4 as a downstream mediator of hsa-let-7e-5p. In an animal model of AD, knockdown of circ_0000006 and circ_0000160 also showed protective effects against aortic septation. Overall, our findings indicate that the upregulation of circ_0000006 and circ_0000160 contributes to the progression from AA to AD by influencing abnormal phenotypic changes, migration, and proliferation of VSMCs. The Hsa-let-7e-5p/UBQLN4 axis may play a critical role in AD development. Targeting circ_0000006 and circ_0000160 could be a potential therapeutic strategy for preventing the progression of AD.

Deoxypodophyllotoxin Mediates Autophagy Death through Inhibition of GRP78 in Human Osteosarcoma.

BACKGROUND: Glucose-regulated protein 78 (GRP78), as a chaperone protein, can protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or cell cycle arrest. OBJECT: This study was performed to demonstrate the molecular mechanism by which DPT attenuates osteosarcoma progression through GRP78. METHODS: Natural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)- Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'- deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma cells treated with DPT. We constructed an in vivo mouse model of DPT drug therapy and carried out immunohistochemical detection of xenografts. The treated osteosarcoma cells were analyzed using bioinformatics and electron microscopy. The data were analyzed finally. RESULTS: DPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated by the overexpression of GRP78, characterized by the inactivation of the caspase cascade. The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagyassociated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR) axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and blocked the apoptotic cascade. CONCLUSION: Combination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells.

Free flap transplantation combined with skin grafting and vacuum sealing drainage for repair of circumferential or sub-circumferential soft-tissue wounds of the lower leg.

BACKGROUND: This study is aimed at evaluating the operation techniques and clinical significance of free flap transplantation combined with skin grafting and vacuum sealing drainage (VSD) in repairing severe traumatic extensive circumferential or semi-circumferential soft-tissue defects of the lower leg. MATERIAL AND METHODS: Thirty patients with severe lower leg injuries were treated by free flap transplantation combined with skin grafting and VSD from January 2008 to June 2011. The size of the wounds ranged from 23×8 cm to 44×28 cm and all affected more 70% of the low leg circumferential area. Wounds were complicated by exposure, necrosis, or infection of deep tissues. The wounds were first debrided and covered by VSD. When the condition of the wound had improved (5 to 7 days later), free flaps were harvested to reconstruct damaged tissue and skin grafts and VSD was used to cover granulation tissues around the transplanted flap. RESULTS: Granulation tissues developed and the area requiring flap cover decreased in all 30 patients after debridement and VSD. In 28 of 30 cases, the transplanted flaps grew well without complication. Peripheral necrosis was observed in only 2 cases, which required a second debridement and skin graft. Ten wound areas covered by grafts were left with scattered peripheral wounds, which healed with the help of 1 more skin graft or dressing change. Morphological appearance and functional recovery were satisfactory in all 30 cases. CONCLUSIONS: Initial debridement and the temporary VSD cover followed after several days by free flap transplantation combined with skin grafting and VSD protection is a reliable treatment regimen for traumatic large circumferential or sub-circumferential soft tissue wounds of the lower leg with deep tissue exposure.

Investigation on Imaging Features and Clinical Significance of Cardiac CT in Comprehensive Evaluation of Aortic Valve and Root before Percutaneous Aortic Valve Replacement.

Medical imaging feature analysis is the basis of medical image processing and analysis. The solution of this problem not only directly affects the successful application of computer graphics and image technology in medicine but also has important theoretical and practical significance. In this paper, the imaging characteristics and clinical significance are discussed by studying the comprehensive evaluation of aortic valve and root before aortic valve replacement. In recent years, preoperative comprehensive evaluation of the aortic valve and root has been gradually carried out. Compared with traditional methods, minimally invasive surgery brings more accurate diagnosis to patients, quick recovery and discharge after surgery, and less pain. This study retrospectively includes patients with severe aortic stenosis who underwent TAVR with routine computed tomography. Based on CT images, the determination and grouping of bicuspid aortic valve and tricuspid aortic valve were completed. Thirteen cross-sectional levels of the aorta-iliac-femoral vascular access were completed. The results showed that 3 people had stroke (17.6%) and 5 people had myocardial infarction (29.4%) during the follow-up period. Atrial fibrillation occurred in 5 patients (29.4%), permanent pacemaker implantation was performed in 1 patient (5.9%), and acute kidney injury occurred in 7 patients (41.2%). No patient died due to surgery-related causes, and the analysis of imaging features and clinical significance in the preoperative comprehensive evaluation of the aortic valve and root played a crucial role. In the training stage, the principal component analysis method was used to train the shape, and the model of the shape intensity of the aortic valve and the shape change of each principal component was obtained. The most probable aortic valve region in the target image was obtained by matching the similarity of all atlases, and the correct aortic valve segmentation was obtained by using the first level set of shape intensity. The experimental part verified the accuracy of the algorithm.

Deep Hierarchical Vision Transformer for Hyperspectral and LiDAR Data Classification.

In this study, we develop a novel deep hierarchical vision transformer (DHViT) architecture for hyperspectral and light detection and ranging (LiDAR) data joint classification. Current classification methods have limitations in heterogeneous feature representation and information fusion of multi-modality remote sensing data (e.g., hyperspectral and LiDAR data), these shortcomings restrict the collaborative classification accuracy of remote sensing data. The proposed deep hierarchical vision transformer architecture utilizes both the powerful modeling capability of long-range dependencies and strong generalization ability across different domains of the transformer network, which is based exclusively on the self-attention mechanism. Specifically, the spectral sequence transformer is exploited to handle the long-range dependencies along the spectral dimension from hyperspectral images, because all diagnostic spectral bands contribute to the land cover classification. Thereafter, we utilize the spatial hierarchical transformer structure to extract hierarchical spatial features from hyperspectral and LiDAR data, which are also crucial for classification. Furthermore, the cross attention (CA) feature fusion pattern could adaptively and dynamically fuse heterogeneous features from multi-modality data, and this contextual aware fusion mode further improves the collaborative classification performance. Comparative experiments and ablation studies are conducted on three benchmark hyperspectral and LiDAR datasets, and the DHViT model could yield an average overall classification accuracy of 99.58%, 99.55%, and 96.40% on three datasets, respectively, which sufficiently certify the effectiveness and superior performance of the proposed method.

Intraluminal Diverticular Duodenal Duplication With Recurrent Abdominal Pain: A Case Report.

Duodenal duplication is a rare congenital anomaly and may manifest as pancreatitis, gastrointestinal bleeding, abdominal pain, perforation, and obstruction. Here, we present a case of intraluminal diverticular duodenal duplication (IDDD) in a child with recurrent abdominal pain caused by a large hole-like structure in the duodenal bulb. This condition has rarely been reported. An 11-year-old boy presented with recurrent attacks of abdominal pain. Upper endoscopy examination and barium swallowing led to an initial diagnosis of IDDD; this diagnosis was confirmed by operative findings and histopathological signs. He underwent a subtotal excision and duodenal anastomosis. No serious complications occurred following treatment. The patient was followed up for 8 months, and his condition improved without symptoms.

Poly[[tetra-aqua-tetra-kis-[µ(3)-5-(pyridine-4-carboxamido)-isophthalato]cobalt(II)dierbium(III)] tetra-hydrate].

In the centrosymmetric polymeric title compound, {[CoEr(2)(C(14)H(8)N(2)O(5))(4)(H(2)O)(4)]·4H(2)O}(n), the Er(III) cation has a coordination number of eight and is surrounded by seven carboxyl-ate O atoms from four 5-(pyridine-4-carboxamido)-isophthalate (L) ligands and one water mol-ecule, forming a distorted square-anti-prismatic arrangement. The Co(II) cation is located on an inversion center and is coordinated by two pyridine N atoms, two carboxyl-ate O atoms and two water mol-ecules in a distorted octa-hedral geometry. The asymmetric unit contains two anionic L ligands. One bridges two Er(III) cations and one Co(II) cation through two carboxyl-ate groups and one pyridine N atom, while the other bridges two Er(III) cations and one Co(II) cation through two carboxyl-ate groups. Extensive O-H⋯O, O-H⋯N and N-H⋯O hydrogen-bonding inter-actions are present in the crystal, involving all uncoordinated water mol-ecules and the uncoordinated pyridine N atom of one of the ligands bonded to an adjacent coordinated water mol-ecule. The title compound is isotypic with the gadolinium analogue.

Two new isomeric zinc(II) metal-organic frameworks based on 1,5-bis(2-methyl-1H-imidazol-1-yl)pentane and 5-methylisophthalate ligands.

Many factors, such as temperature, solvent, the central metal atom and the type of coligands, may affect the nature of metal-organic frameworks (MOFs) and the framework formation in the self-assembly process, which results in the complexity of these compounds and the uncertainty of their structures. Two new isomeric ZnII metal-organic frameworks (MOFs) based on mixed ligands, namely, poly[[µ-1,5-bis(2-methyl-1H-imidazol-1-yl)pentane-κ2N3:N3'](µ-5-methylisophthalato-κ2O1:O3)zinc(II)], [Zn(C9H6O4)(C13H20N4)]n, (I), and poly[[µ-1,5-bis(2-methyl-1H-imidazol-1-yl)pentane-κ2N3:N3'](µ3-5-methylisophthalato-κ3O1:O1':O3)(µ3-5-methylisophthalato-κ4O1:O1':O3,O3')dizinc(II)], [Zn2(C9H6O4)2(C13H20N4)]n, (II), have been synthesized under hydrothermal conditions and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis and thermogravimetric analysis. Complex (I) displays a two-dimensional layer net, while complex (II) exhibits a twofold interpenetrating three-dimensional framework. Both complexes show high stability and good fluorescence in the solid state at room temperature.

Effects of simulated weightlessness on bone metabolism in rats at different ages.

OBJECTIVE: To compare the effects of simulated weightlessness on age-related bone metabolism and on the mechanical parameters of the weight-bearing bones of rats at different ages. METHODS: Two-month-old and 6-month-old rats (8 in each group) were both subjected to tail suspension test for up to 4 weeks, with 2 groups of rats of corresponding ages (n=8) serving as control. The bone metabolism markers, biomechanical parameters of the femurs, along with the growth and mineral contents of the tibia, were respectively measured and compared with those of the controls. RESULTS: The bone formation markers, alkaline phosphatase and osteocalcin levels, dropped drastically in both groups of rats undergoing tail suspension test (P<0.01), which also induced significant hypocalcaemia (P<0.01). Bone material loss of the tibia occurred in both groups of rats receiving the test (P<0.01) whose effect on the volume and mass of fresh tibia was age-related (P<0.05), but the degree of mineral loss was not consistent with calcium loss in rats at different ages. Except for elastic deformation (P>0.05), both structural and biomechanical properties altered significantly after tail suspension test (P<0.01), and the changes of maximum deformation and maximum load were related to the age of the rats (P<0.05). CONCLUSION: The result is an age-related difference in the response of bone metabolism to simulated weightlessness.

Changes of serum MDA and SOD levels in ischemia-reperfusion injuries of the limbs in rats preconditioned with heat stress.

OBJECTIVE: To study the effect of pretreatment with heat stress on ischemia-reperfusion injuries of the limbs in rats. METHODS: Rat models of ischemia-reperfusion injury were established with or without prior heat stress treatment, in which serum malondialdehyde (MDA) level and superoxide dismutase (SOD) activities were measured by means of thiobarbituric acid and nitroblue tetrazolium respectively. RESULTS: Comparison between ischemia-reperfusion group and the control group revealed significantly elevated MDA levels (P<0.01) and depressed SOD activities (P<0.01) in the condition of ischemia-reperfusion injury. Pretreatment with heat stress, however, significantly lowered the elevated MDA levels (P<0.01) and enhanced SOD activities (P<0.01) during ischemia-reperfusion injury. CONCLUSION: Pretreatment with heat stress can enhance the activity of SOD to remove free oxygen radicals in the cells.

[Isolation and purification of diarylheptanoids from Alpinia officinarum Hance by high-speed counter-current chromatography].

Three diarylheptanoids were isolated and purified from Alpinia officinarum Hance by high-speed counter-current chromatography (HSCCC). A two-phase solvent system composed of hexane-ethyl acetate-methanol-water (2: 3: 1.75: 1, v/v/v/v) was used. The lower phase was used as the stationary phase. From 122.20 mg petroleum ether extract of A. officinarum, 5R-hydroxy-7-(4-hydroxy-3-methoxyphenyl )-1-phenyl-3-heptanone (7.37 mg), 7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-4E-en-3-heptanone (9.11 mg) and 1,7-diphenyl-4E-en-3-heptanone (15.44 mg) with purities over 93% were obtained within 140 min in one-step separation by HSCCC under the conditions of a flow rate of 1.5 mL/min and 858 r/min. The obtained compounds were analyzed by high performance liquid chromatography to provide their purities, and their structures were confirmed by using mass spectrometry, 1H-nuclear magnetic resonance (1H-NMR) and 13C-NMR. The established HSCCC method is relatively simple, fast and suitable for the isolation and purification of diarylheptanoids from A. officinarum.