Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). Methods: We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. Results: We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Conclusion: Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

The Effect of Dexmedetomidine on the Prognosis of Mechanically Ventilated Patients with Sepsis: A Meta-Analysis of Randomized Controlled Trials.

Background: Dexmedetomidine (Dex), as a new and highly selective α2 adrenergic receptor agonist, has been widely used in mechanically ventilated patients. In the present study, we used meta-analysis to study the effect of Dex on the prognosis of mechanically ventilated patients with sepsis. Methods: We searched PubMed, Cochrane clinical trial, EMBASE, Web of Science, and Chinese biomedical literature database to analyze relevant literature published from January 2000 to January 2021. We conducted the quality evaluation and data extraction for studies that met the inclusion criteria. RevMan 5.3 software was used to perform a meta-analysis of the 28-day mortality, hospital mortality, the length of ICU stay, and other adverse indicators. Results: Ten randomized controlled trials (RCTs) that met the inclusion criteria were finally included, including 9 RCTs in English and one in Chinese, with a total of 892 patients. Our meta-analysis results found that in mechanically ventilated patients with sepsis, Dex could significantly reduce the length of ICU stay (P=0.02), but did not reduce the patients' 28-day mortality (P=0.06), hospital mortality (P=0.17) and ventilator-free days (P=0.33). Furthermore, our meta-analysis results also found that Dex had no significant effect on the respiratory rate (P=0.53), heart rate (P=0.02), mean arterial pressure (P=0.63), the level of creatinine (P=0.82) and continuous renal replacement therapy (P=0.39) in mechanically ventilated patients with sepsis. Conclusion: In mechanically ventilated patients with sepsis, Dex can reduce the length of ICU stay, but which cannot reduce the 28-day mortality, hospital mortality, and ventilator-free days.

Visible-light-induced photooxidation of ruthenium(II) complex with 2,2'-biimidazole-like ligand by singlet oxygen.

Four new ruthenium(II) complexes [Ru(bpy)2(TMBiimH2)](ClO4)2 (Ru-5; bpy is 2,2'-bipyridine and TMBiimH2 is 4,5,4',5'-tetramethyl-2,2'-biimidazole), [Ru(bpy)2(L1H2)](ClO4)2·H2O (Ru-6; L1H2 is 4,5-dimethyl-2-(N,N-diacetyl)carboximidamide-1H-imidazole), [Ru(bpy)2(L2H2)](ClO4)2 (Ru-7; L2H2 is N(1),N(1),N(2),N(2)-tetrakis(acetyl)ethanediimidamide), and [Ru(phen)2(TMBiimH2)](ClO4)2 (Ru-8; phen is 1,10'-phenanthroline) have been synthesized and characterized. Their photophysical and electrochemical properties have been studied and compared to the previously reported [Ru(bpy)2(BiimH2)](PF6)2 (Ru-1), [Ru(bpy)2(BbimH2)](PF6)2 (Ru-2), [Ru(bpy)2(DMBbimH2)](PF6)2 (Ru-3), and [Ru(bpy)2(TMBbimH2)](PF6)2 (Ru-4). Under irradiation with either sunlight or household light in atmosphere, Ru-5 reacts with molecular oxygen to produce Ru-6 in an acetonitrile solution with a relatively high concentration and Ru-7 in a methanol or dilute acetonitrile solution, respectively. The mechanism studies show that singlet oxygen is the reactive oxygen species in the ring-opening reaction and the photooxidation reaction is solvent- and concentration-dependent. The photoreaction product Ru-6 is an intermediate, which has been isolated and structurally characterized by single-crystal X-ray diffraction. Ru-6 is stable in the solid state and an acetonitrile solution with a high concentration, but can be further oxidized to Ru-7 in a methanol or dilute acetonitrile solution.

Photophysical, electrochemical and anion sensing properties of Ru(II) bipyridine complexes with 2,2'-biimidazole-like ligand.

A new anion sensor [Ru(bpy)(2)(DMBbimH(2))](PF(6))(2) (3) (bpy is 2, 2'-bipyridine and DMBbimH(2) is 7,7'-dimethyl-2,2'-bibenzimidazole) has been developed. Its photophysical, electrochemical and anion sensing properties are compared with two previously investigated systems, [Ru(bpy)(2)(BiimH(2))](PF(6))(2) (1) and [Ru(bpy)(2)(BbimH(2))](PF(6))(2) (2) (BiimH(2) is 2,2'-biimidazole and BbimH(2) is 2,2'-bibenzimidazole). The high acidity of the N-H fragments in these complexes make them easy to be deprotonated by strong basic anions such as F(-) and OAc(-), and they form N-H···X hydrogen bonds with weak basic anions like Cl(-), Br(-), I(-), NO(3)(-), and HSO(4)(-). Complex 3 displays strong hydrogen bonding with these 5 weak basic anions, with binding constants between 17,000 and 21,000, which are larger than those observed in complex 1, with binding constants between 3300 and 5700, and in complex 2, which shows no hydrogen bonding toward Cl(-), Br(-), I(-), and NO(3)(-), and forms considerable hydrogen bonds with HSO(4)(-) with a binding constant of 11,209. These hydrogen bonding behaviours give different NMR, emission and electrochemical responses. The different anion binding affinity of these complexes may be mainly attributed to their different pK(a1) values, 7.2 for 1, 5.7 for 2, and 6.2 for 3. The additional methyl groups at the 7 and 7' positions of complex 3 may also play an important role in the enhancement of anion binding strength.

Prenatal alcohol exposure induces long-term changes in dendritic spines and synapses in the mouse visual cortex.

AIMS: To study the long-term changes of dendritic spine and synapse taking place in a mouse model of fetal alcohol spectrum disorders (FASDs). METHODS: Pregnant mice were intubated daily with ethanol (EtOH) from E5 to parturition. A DiI diolistic method was used to label dendritic spines of pyramidal cells in the visual cortex of EtOH-exposed and control pups over the period from postnatal (P) day P0 to P30; synaptic ultrastructure was also analyzed using transmission electron microscopy. RESULTS: Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length. The changes were dose dependent and persisted to P30. Ultrastructural changes were also observed, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls; ultrastructural changes also persisted to P30. CONCLUSIONS: Prenatal alcohol exposure is associated with long-term changes in dendritic spines and synaptic ultrastructure; these alterations probably reflect the developmental retardation of dendritic spines and synapses in visual cortex. These long-term changes are likely to contribute to lifelong mental retardation associated with childhood FASDs.

Expression of the apoptosis-related proteins caspase-3 and NF-kappaB in the hippocampus of Tg2576 mice.

OBJECTIVE: To investigate the relations between neuroapoptosis and the onset and development of Alzheimer's disease (AD), especially the role of NF-kappaB in the regulation of neuroapoptosis. METHODS: Caspase-3 and NF-kappaB (p50) expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. RESULTS: Both neuronal apoptosis and NF-kappaB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF-kappaB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P < 0.01 or P < 0.05). Linear regression analyses of caspase-3 and NF-kappaB expression demonstrated a correlation between neuroapoptosis and activity of NF-kappaB. CONCLUSION: The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-kappaB activity suggests a role of NF-kappaB in hippocampal neuroapoptosis.

Ruthenium(II) 2,2'-bibenzimidazole complex as a second-sphere receptor for anions interaction and colorimeter.

A ruthenium(II) complex [Ru(bpy) 2(H 2bbim)](PF 6) 2 ( 1) as anions receptor has been exploited, where Ru(II)-bpy moiety acts as a chromophore and the H 2bbim ligand as an anion binding site. A systematic study suggests that 1 interacts with the Cl (-), Br (-), I (-), NO 3 (-), HSO 4 (-), and H 2PO 4 (-) anions via the formation of hydrogen bonds. Whereas 1 undergoes a stepwise process with the addition of F (-) and OAc (-) anions: formation of the monodeprotonated complex [Ru(bpy) 2(Hbbim)] with a low anion concentration, followed by the double-deprotonated complex [Ru(bpy) 2(bbim)], in the presence of a high anion concentration. These stepwise processes concomitant with the changes of vivid colors from yellow to orange brown and then to violet can be used for probing the F (-) and OAc (-) anions by naked eye. The deprotonation processes are not only determined by the basicity of the anion but also related to the strength of hydrogen bonding, as well as the stability of the formed compounds. Moreover, a double-deprotonated complex [Ru(bpy) 2(bbim)].CH 3OH.H 2O ( 3) has been synthesized, and the structural changes induced by the deprotonation has also been investigated. In addition, complexes [Ru(bpy) 2(Hbbim)] 2(HOAc) 3Cl 2.12H 2O ( 2), [Ru(bpy) 2(Hbbim)](HCCl 3CO 2)(CCl 3CO 2).2H 2O ( 4), and [Ru(bpy) 2(H 2bbim)](CF 3CO 2) 2.4H 2O ( 5) have been synthesized to observe the second sphere coordination between the Ru(II)-H 2bbim moiety and carboxylate groups via hydrogen bonds in the solid state.

Anion-selective interaction and colorimeter by an optical metalloreceptor based on ruthenium(II) 2,2'-biimidazole: hydrogen bonding and proton transfer.

A new anion sensor [Ru(bpy)2(H2biim)](PF6)2 (1) (bpy = 2,2'-bipyridine and H2biim = 2,2'-biimidazole) has been developed, in which the Ru(II)-bpy moiety acts as a chromophore and the H2biim ligand as an anion receptor via hydrogen bonding. A systematic investigation shows that 1 is an eligible sensor for various anions. It donates protons for hydrogen bonding to Cl-, Br-, I-, NO3-, HSO4-, H2PO4-, and OAc- anions and further actualizes monoproton transfer to the OAc- anion, changing color from yellow to orange brown. The fluoride ion has a high affinity toward the N-H group of the H2biim ligand for proton transfer, rather than hydrogen bonding, because of the formation of the highly stable HF2- anion, resulting in stepwise deprotonation of the two N-H fragments. These processes are signaled by vivid color changes from yellow to orange brown and then to violet because of second-sphere donor-acceptor interactions between Ru(II)-H2biim and the anions. The significant color changes can be distinguished visually. The processes are not only determined by the basicity of anion but also by the strength of hydrogen bonding and the stability of the anion-receptor complexes. The design strategy and remarkable photophysical properties of sensor 1 help to extend the development of anion sensors.