Reform in teaching preclinical pathophysiology.

Pathophysiology is a scientific discipline that studies the onset and progression of pathological conditions and diseases, and pathophysiology is one of the core courses in most preclinical medical curricula. In China, most medical schools house a Department of Pathophysiology, in contrast to medical schools in many developed countries. The staff in Chinese Departments of Pathophysiology generally consists of full-time instructors or lecturers who teach medical students. These lecturers are sometimes lacking in clinic knowledge and experiences. To overcome this, in recent years, we have been trying to bring new trends in teaching pathophysiology into our curriculum. Our purpose in writing this article was to share our experiences with our colleagues and peers worldwide in the hope that the insights we have gained in pathophysiology teaching will be of some value to educators who advocate teaching reform in medical schools.

Association of serum Dkk-1 levels with ß-catenin in patients with postmenopausal osteoporosis.

Wnt signaling plays an important role in the bone development and remodeling. The Wnt antagonist Dkk-1 is a potent inhibitor of bone formation. The aims of this study were firstly to compare the serum Dkk-1 levels in postmenopausal osteoporosis patients with age-matched healthy controls, and secondly, to assess the possible relationship between Dkk-1 and ß-catenin, sclerostin, or bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] in the setting of postmenopausal osteoporosis. A total of 350 patients with postmenopausal osteoporosis and 150 age-matched healthy controls were enrolled, and the serum levels of Dkk-1, ß-catenin, sclerostin, OPG, and RANKL were detected by ELISA, and bone turnover markers [CTX, PINP, N-MID-OT and 25(OH)D] were measured by Roche electrochemiluminescence system in two groups. Serum Dkk-1 levels were significantly higher in postmenopausal osteoporosis group than in control group (P<0.001). Univariate analyses revealed that serum Dkk-1 levels were weakly negatively correlated to ß-catenin (r=-0.161, P=0.003) and OPG (r=-0.106, P=0.047), while multiple regression analysis showed a negative correlation between serum Dkk-1 levels with ß-catenin (ß=-0.165, P=0.009) and BMD (ß=-0.139, P=0.027), and a positive correlation between serum Dkk-1 levels and CTX (ß=0.122, P=0.040) in postmenopausal osteoporosis group. No similar correlations ware observed in control group. The results provided evidence for the role of Dkk-1 in bone metabolism and demonstrated the link of Dkk-1 and Wnt/ß-catenin in some ways.

Three coordination polymers based on 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether: Synthesis, structure and selective fluorescent sensing properties.

Three CPs [Zn2(PDA)2(BMIOPE)2·3H2O]n (1), [Co(Br-BDC)(BMIOPE)]n (2) and [Co(MIP)(BMIOPE)]n (3) were synthesized by solvothermal method based on dual-ligand strategy (H2PDA, Br-H2BDC, BMIOPE and H2MIP are 1,3-phenylenediacetic acid, 5-bromo-isophthalic acid, 4,4'-bis(2-methylimidazol-1-yl)diphenyl ether and 5-methylisophthalic acid, respectively). Complexes 1 and 3 exhibit twofold parallel interwoven sql nets. Complex 2 is 2D layer structure. The luminescence property investigations showed that complexes 1-3 could act as multi-responsive fluorescent sensors to detect UO22+, Cr2O72- and CrO42- and nitrofurantoin (NFT) through fluorescence turn-off process, presenting excellent sensitivity and selectivity. Finally, the possible fluorescent quenching mechanisms of complexes 1-3 toward the above pollutants are also further investigated by employing spectroscopic methods and quantum chemical calculations. The fluorescence lifetime measurements manifest the mechanism of fluorescence quenching is static quenching process.

Cervical cancer with polymorphism in MTHFR C677T gene: a systematic review and meta-analysis.

To perform a meta-analysis investigating the association of MTHFR C677T polymorphism and susceptibility of cervical cancer. All case-control studies published in English and Chinese with estimates of the relationship between MTHFR C677T polymorphism and risk of cervical cancer were analyzed using odds ratio (OR) with 95 % confidence interval (CI). A total of 10 studies (2,023 cases and 2,570 controls) were included in the meta-analysis. No significant association was observed between T allele and C allele (OR = 0.90; 95 %CI = 0.70-1.17; P = 0.43), and for genotype TT versus CC (OR = 1.09; 95 %CI = 0.74-1.61; P = 0.67), CT versus CC (OR = 0.95; 95 %CI = 0.75-1.20; P = 0.65), CT + TT versus CC (OR = 0.91; 95 %CI = 0.66-1.24; P = 0.55). The current meta-analysis results suggest that the MTHFR C677T polymorphism may not be associated with cervical cancer.

A novel two-dimensional coordination polymer: poly[diaquatetra-µ2-chlorido-[µ2-2,2'-(piperazine-1,4-diium-1,4-diyl)diacetate]dicadmium(II)].

In the crystal structure of the title two-dimensional metal-organic polymeric complex, [Cd2Cl4(C8H14N2O4)(H2O)2]n, the asymmetric unit contains a crystallographically independent Cd(II) cation, two chloride ligands, an aqua ligand and half a 2,2'-(piperazine-1,4-diium-1,4-diyl)diacetate (H2PDA) ligand, the piperazine ring centroid of which is located on a crystallographic inversion centre. Each Cd(II) centre is six-coordinated in an octahedral environment by an O atom from an H2PDA ligand and an O atom from an aqua ligand in a trans disposition, and by four chloride ligands arranged in the plane perpendicular to the O-Cd-O axis. The complex forms a two-dimensional layer polymer containing [CdCl2]n chains, which are interconnected into an extensive three-dimensional hydrogen-bonded network by C-H···O, C-H···Cl and O-H···O hydrogen bonds.

A one-dimensional coordination polymer with a three-dimensional supramolecular framework: catena-poly[[[(3,4,7,8-tetramethyl-1,10-phenanthroline)cadmium(II)]-µ3-4,4'-sulfonyldibenzoato] trihydrate].

In the title mixed-ligand metal-organic polymeric compound, {[Cd(C14H8O6S)(C16H16N2)]·3H2O}n, the asymmetric unit contains a crystallographically unique Cd(II) atom, one doubly deprotonated 4,4'-sulfonyldibenzoic acid (H2SDBA) ligand, one 3,4,7,8-tetramethyl-1,10-phenanthroline (TMPHEN) molecule and three solvent water molecules. Each Cd(II) centre is six-coordinated by two O atoms from a chelating carboxylate group of a SDBA(2-) ligand, two O atoms from monodentate carboxylate groups of two different SDBA(2-) ligands and two N atoms from a chelating TMPHEN ligand. There are two coordination patterns for the carboxylate groups of the SDBA(2-) ligand, with one in a µ1-η(1):η(1) chelating mode and the other in a µ2-η(1):η(1) bis-monodentate mode. Single-crystal X-ray diffraction analysis revealed that the title compound is a one-dimensional double-chain polymer containing 28-membered rings based on the [Cd2(CO2)2] rhomboid subunit. More interestingly, a chair-shaped water hexamer cluster is observed in the compound.

MicroRNA-29a-3p Accelerates Inflammatory Damage in Neonatal Pneumonia Via Targeting Krüppel-like Factor 4.

Neonatal pneumonia (NP) is a frequently occurring illness during the neonatal phase. The study investigated the molecular process and the role of microRNA (miR)-29a-3p in NP. Peripheral blood was collected from NP patients and healthy newborns. Human lung fibroblasts cell line (WI-38) were treated with lipopolysaccharide (LPS)) to establish a cellular model for NP. Then, miR-29a-3p and Krüppel-like Factor 4 (KLF4) levels were detected by RT-qPCR or Western blot. The relationship between miR-29a-3p and KLF4 was confirmed by dual luciferase reporter gene assay. Cell survival was assessed using the CCK-8 assay, whereas the levels of interleukin-6, tumor necrosis factor-α, and IL-1ß were quantified using ELISA. Additionally, apoptosis was evaluated through flow cytometry. Meanwhile, Bax and Bcl-2 were detected by RT-qPCR. Neonatal rats were administered LPS intraperitoneally (3 mg/kg) to induce NP, and pathological injury and inflammatory reaction were analyzed. MiR-29a-3p was elevated but KLF4 was silenced in NP patient's serum, LPS-treated WI-38 cell line, and LPS-treated newborn rats. Silence of miR-29a-3p or elevation of KLF4 constrained cell proliferation with inflammation of LPS-treated WI-38 cell line. MiR-29a-3p immediately targeted KLF4. Additionally, silence of miR-29a-3p alleviated LPS-stimulated lung injury and inflammation in neonatal rats. The protective action of silenced miR-29a-3p in LPS-treated WI-38 cell line and newborn rats was turned around by silencing KLF4. This study demonstrates originally that miR-29a-3p boosts inflammatory damage in NP via targeting KLF4, offering a basis for clinically diagnosing and treating NP.

A fivefold interpenetrating diamond-like three-dimensional metal-organic framework: poly[(µ2-benzene-1,4-diacetato)[µ2-1,6-bis(1,2,4-triazol-1-yl)hexane]zinc(II)].

In the mixed-ligand metal-organic title polymeric compound, [Zn(C(10)H(8)O(4))(C(10)H(16)N(6))](n) or [Zn(PBEA)(BTH)](n) [H(2)PBEA is benzene-1,4-diacetic acid and BTH is 1,6-bis(1,2,4-triazol-1-yl)hexane], the asymmetric unit contains a Zn(II) atom, one half of a BTH ligand and one half of a doubly deprotonated H(2)PBEA ligand. Each Zn(II) centre lies on a crystallographic twofold rotation axis and is four-coordinated by two O atoms from two distinct PBEA(2-) ligands and two N atoms from two different BTH ligands in a {ZnO(2)N(2)} coordination environment. The three-dimensional topology of the title compound corresponds to that of a fivefold interpenetrating diamond-like metal-organic framework.

A new three-dimensional cadmium(II) coordination polymer based on bis[4-(2-methylimidazol-1-yl)phenyl]methanone: synthesis, structure and properties.

A novel three-dimensional CdII coordination polymer, namely, poly[[(µ3-benzene-1,4-diacetato)(µ2-benzene-1,4-diacetato)bis{µ2-bis[4-(2-methylimidazol-1-yl)phenyl]methanone}dicadmium(II)] tetartohydrate], {[Cd(C10H8O4)(C21H18N4O)]·0.25H2O}n or {[Cd(PBEA)(MIPMO)]·0.25H2O}n, (I), was synthesized by the hydrothermal method using benzene-1,4-diacetic acid (H2PBEA), bis[4-(2-methylimidazol-1-yl)phenyl]methanone (MIPMO) and Cd(NO3)2·6H2O. The title compound was structurally characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopy and thermogravimetric analysis, and exhibits a three-dimensional pillar-layer framework based on CdII-PBEA layers and MIPMO pillars, which can be simplified into a pcu topological network. The title compound displays a highly selective and sensitive sensing for Fe3+ ions in aqueous solution. In addition, it displays a high photocatalytic activity for the degradation of methylene blue (MB) in water under UV light irradiation.

Looking for high energy density compounds applicable for propellant among the derivatives of DPO with -N3, -ONO2, and -NNO2 groups.

The derivatives of DPO (2,5-dipicryl-1,3,4-oxadiazole) are optimized to obtain their molecular geometries and electronic structures at the DFT-B3LYP/6-31G* level. The bond length is focused to primarily predict thermal stability and the pyrolysis mechanism of the title compounds. Detonation properties are evaluated using the modified Kamlet-Jacobs equations based on the calculated densities and heats of formation. It is found that there are good linear relationships between density, detonation velocity, detonation pressure, and the number of azido, nitrate, and nitramine groups. According to the largest exothermic principle, the relative specific impulse is investigated by calculating the enthalpy of combustion (ΔH(comb)) and the total heat capacity (C(p,gases)). It is found that the introduction of -N(3), -ONO(2), and -NNO(2) groups could increase the specific impulses and II-4, II-5, and III-5 are potential candidates for High Energy Density Materials (HEDMs). The effect of the azido, nitrate, and nitramine groups on the structure and the properties is discussed.

Poly[(µ3-benzene-1,4-diacetato)[µ2-1,4-bis(1,2,4-triazol-1-yl)butane]cadmium(II)]: self assembly into a three-dimensional supramolecular framework based on [Cd(µ3-benzene-1,4-diacetate)] double chains.

The title compound, [Cd(C(10)H(8)O(4))(C(8)H(12)N(6))](n), crystallizes with an asymmetric unit comprising a divalent Cd(II) atom, a benzene-1,4-diacetate (PBEA(2-)) ligand and a complete 1,4-bis(1,2,4-triazol-1-yl)butane (BTB) ligand. [Cd(PBEA)](n) double chains, arranged parallel to the c axis, are formed through an exo-tridentate binding mode of the PBEA(2-) ligands. These [Cd(PBEA)](n) double chains are pillared by tethering BTB ligands, in which the BTB shows a trans-trans-trans conformation, to establish [Cd(PBEA)(BTB)](n) two-dimensional coordination polymer (4,4)-layer slab patterns. The three-dimensional supramolecular architecture is formed by C-H···O hydrogen bonds and C-H···π interactions.

The coordination polymer poly[bis[µ2-2-(2,2'-bi-1H-imidazol-1-yl)acetato]cadmium].

The title compound, [Cd(C(8)H(7)N(4)O(2))(2)](n), crystallizes in the centrosymmetric triclinic space group P1 with an asymmetric unit consisting of a bivalent Cd(II) atom and two 2-(2,2'-bi-1H-imidazol-1-yl)acetate (BDAC(-)) anions. Two inversion-related BDAC(-) ligands are oppositely arranged and bind two Cd(II) ions to form a [Cd(2)(BDAC)(2)] rhomboid subunit which is bridged by another BDAC(-) ligand to form an infinite ladder along the a direction containing parallelogram grids. The three-dimensional supramolecular architecture is formed by hydrogen bonds and C-H···π and π-π interactions.

A novel two-dimensional (4,4) network based on dinuclear cadmium secondary building units: poly[(µ5-benzene-1,4-diacetato)[µ2-1,4-bis(1,2,4-triazol-1-yl)butane]cadmium(II)].

In the title mixed-ligand metal-organic polymeric compound, [Cd(C(10)H(8)O(4))(C(8)H(12)N(6))](n) or [Cd(PBEA)(BTB)](n) [H(2)PBEA is benzene-1,4-diacetic acid and BTB is 1,4-bis(1,2,4-triazol-1-yl)butane], the asymmetric unit contains one Cd(II) ion, one BTB molecule and one PBEA(2-) anion. The Cd(II) ion is in a slightly distorted pentagonal-bipyramidal geometry, coordinated by five carboxylate O atoms from three distinct PBEA(2-) anions and by two BTB N atoms. There are two coordination patterns for the carboxylate groups of the PBEA(2-) ligand, one being a µ(1)-η(1):η(1) chelating mode and the other a µ(2)-η(2):η(1) bridging mode, while the BTB molecule shows a trans-trans-trans conformation. The crystal structure is constructed from the secondary building unit (SBU) [Cd(2)(CO(2))(4)N(2)O(2)], in which the two metal centres are held together by two PBEA(2-) linkers. The SBU is connected by BTB and PBEA(2-) bridges to form a two-dimensional grid-like (4,4) layer with meshes of dimensions 14.69 × 11.28 Å.

A New Day 4 Grading System to Assess Embryo Quality in Frozen Embryo Transfer Cycles.

To present a new day 4 (D4) embryo grading system to assess embryos in frozen-thawed embryo transfer (FET) cycles. A new grading system (grades A-E) was developed from the 2011 ESHRE Istanbul Consensus for D4 embryos in FET cycles. Embryos with complete compaction were classified as grade A; those with partial compaction were assigned as grade B; and those without compaction were classified as grades C, D, and E according to their different blastomere number ratio (BNR; number of embryo blastomeres on D4/number of embryo blastomeres on D3, D4/D3). Embryos with a BNR of ≥ 1.5 were defined as grade C, those with a BNR of ≥ 1.2 and < 1.5 were defined as grade D, and those with a BNR of ≥ 1.0 and < 1.2 were defined as grade E. Using this proposed grading model, 5460 embryos with known implantation data were retrospectively analyzed after D4 transfer in FET cycles. The transferred embryos exhibited a similar declining trend in implantation and live birth rates from the top grade A to the lowest grade E. The in vitro fertilization group showed increased implantation rates of grade B and E embryos compared with the intracytoplasmic sperm injection group (grade B: 41.99%, 34.63%, χ2 = 5.84, p < 0.05 and grade E: 18.98%, 14.08, χ2 = 75.62, p < 0.01). Receiver-operating characteristic analysis revealed that our proposed model predicted the implantation outcomes and live birth rates of all embryos (area under the curve = 0.65; 95% confidence interval [CI],0.63-0.66; p < 0.01 and AUC = 0.73; 95%CI, 0.65-0.84; p < 0.001, respectively). This study demonstrates that the new grading system provided by us can be a useful tool for assisting embryo selection via changes in embryo morphology. D4 embryo transfer provides a simple and applicable method for FET cycles in daily practice.

Prediction of flavor and retention index for compounds in beer depending on molecular structure using a machine learning method.

In order to make a preliminary prediction of flavor and retention index (RI) for compounds in beer, this work applied the machine learning method to modeling depending on molecular structure. Towards this goal, the flavor compounds in beer from existing literature were collected. The database was classified into four groups as aromatic, bitter, sulfury, and others. The RI values on a non-polar SE-30 column and a polar Carbowax 20M column from the National Institute of Standards Technology (NIST) were investigated. The structures were converted to molecular descriptors calculated by molecular operating environment (MOE), ChemoPy and Mordred, respectively. By combining the pretreatment of the descriptors, machine learning models, including support vector machine (SVM), random forest (RF) and k-nearest neighbour (kNN) were utilized for beer flavor models. Principal component regression (PCR), random forest regression (RFR) and partial least squares (PLS) regression were employed to predict the RI. The accuracy of the test set was obtained by SVM, RF, and kNN. Among them, the combination of descriptors calculated by Mordred and RF model afforded the highest accuracy of 0.686. R 2 of the optimal regression model achieved 0.96. The results indicated that the models can be used to predict the flavor of a specific compound in beer and its RI value.

New lignans and acetophenone derivatives with α-glucosidase inhibitory activity from the leaves of Melicope patulinervia.

Four new lignans, patulinones A-D (1-4) and three new acetophenone derivatives, patulinones E-G (5-7) were isolated from the leaves of Melicope patulinervia. Their structures were elucidated on the basis of the interpretation of HR-ESIMS, NMR, CD data. All the isolated compounds were evaluated for α-glucosidase inhibitory activity. Of the isolates, compound 4 was found to exhibit the strongest inhibition against α-glucosidase with IC50 value of 6.02 ± 0.46 µM.

New oligomeric neolignans from the leaves of Magnolia officinalis var. biloba.

Six new oligomeric neolignans including two trimeric neolignans (1 and 2) and four dimeric neolignans (3-6) were isolated from the leaves of Magnolia officinalis var. biloba. Their structures were determined based on HR-ESIMS and NMR data, as well as electronic circular dichroism (ECD) calculations. Compound 1 is formed from two obovatol moieties directly linked to an aromatic ring of the remaining obovatol moiety, which is an unprecedented type of linkage between monomers. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1 and 3 showed significantly inhibitory activities with IC50 values of 6.04 and 3.26 µmol·L-1, respectively.

[Impact of magnetic attachment keepers on magnetic resonance imaging examination].

OBJECTIVE: To evaluate the effects of magnetic attachment keepers on MRI images. METHODS: In in vitro part, keepers of MAGFIT EX 400, MAGFIT EX 600 and MAGNEDISC 800 magnetic attachment systems were cast into standard root-caps with different alloy respectively, including nickel-chromium alloy and gold-palladium alloy, or not be cast for contrast. In in vivo part, volunteers with keepers in different position and amount were included. All the specimens and volunteers were imaged by a Siemens SONATA 1.5-T MRI scanner. Extent of the artifacts in every slice was measured. The magnitude of the artifacts and the distortion of the anatomic structures were compared. RESULTS: All kinds of keepers being studied produced obvious MRI artifacts. The extent of MRI artifacts induced by MAGFIT EX 400 keepers, MAGFIT EX 600 keepers and MAGNEDISC 800 keepers are 158.94 mm, 168.52 mm and 173.00 mm, respectively. The images of mental region, tongue, palate, jawbone and sinus were evidently obscured by artifacts in all cases. When keeper was put in the molar region, the keeper-related MRI artifact may obscure the imaging of brain, spinal cord. SE sequence with right-left frequency-encoding direction was more desirable in MRI for the patients with magnetic attachment keepers. CONCLUSION: Keepers of magnetic attachment system did induce obvious artifacts in MRI examination.

[Imaging and quantitative measurement of brain extracellular space using MRI Gd-DTPA tracer method].

OBJECTIVE: To observe the diffusion of Gd-DTPA in brain extracellular space (ECS) by magnetic resonance imaging(MRI) and investigate the feasibility of ECS measurement by using MRI tracer method in vivo. METHODS: 2 microL Gd-DTPA was introduced into ECS by caudate nucleus according to stereotaxic atlas in 8 Sprague Dawley(SD) rats (male, 280-320 g). The MRI scans were performed at 1 h, 3 h, 6 h, 9 h and 12 h respectively after administration. MRI appearances of Gd-DTPA diffusion and distribution was observed and compared. The MRI signal enhancement was measured at each time point. The neuroethology assessment was performed after MRI scanning at 12 h. RESULTS: The injection was accurate at the center of the caudate nucleus in 6 rats, while, at the capsula externa in other 2 rats. Gd-DTPA diffused isotropically after it was introduced into caudate nucleus, which spread into lateral cortex at 3 h. The MRI signal enhancement distributed mainly in the middle cerebral artery territory. A significant difference was found between the signal enhancement ratio at 1 h and that at 3 h in the original point of caudate nucleus (t=95.63, P<0.01), and the signal enhancement attenuated following the exponential power function y=1.7886x(-0.1776) (R2=0.94). In 2 rats with the injection point at capsula externa, Gd-DTPA diffused anisotropically along the fiber track of white matter during 1 h to 3 h, and spread into the lateral cortex at 6 h. CONCLUSION: The diffusion and clearance of Gd-DTPA in brain ECS could be monitored and measured quantitatively in vivo by MRI tracer method.

Ce(OTf)3-Catalyzed Multicomponent Reaction of Alkynyl Carboxylic Acids, tert-Butyl Isocyanide, and Azides for the Assembly of Triazole-Oxazole Derivatives.

Cerium(III) triflate-catalyzed multicomponent reactions between alkynyl carboxylic acids, tert-butyl isocyanide, and organic azides have been developed. In the presence of Ce(OTf)3 (10 mol %), the cascade reaction of one molecule of alkynyl carboxylic acid with three molecules of tert-butyl isocyanides proceeds chemoselectively and regioselectively via a triple and ordered isocyanide insertion process at room temperature, and then the cesium-catalyzed [3 + 2] cycloaddtion reaction between the resulted alkynyl oxazole and organic azides was further initiated by the temperature elevation (100 °C), thereby leading to multisubstituted triazole-oxazole derivatives in practical, time-saving, one-pot operations. Furthermore, some of the synthesized target compounds showed potential anticancer activities against MGC803 (human gastric cancer cell) with IC50 values below 20 µmol L-1.