Pregnancy related adverse events and congenital disorders associated with fluoroquinolones: A real-world pharmacovigilance study of the FDA adverse event reporting system (FAERS).

Background: Fluoroquinolones, including ciprofloxacin, levofloxacin, and moxifloxacin, are extensively employed as broad-spectrum antibacterial agents. However, their use is discouraged during pregnancy due to potential adverse events (AEs). The aim of this study is to systematically investigate the association between fluoroquinolones (specifically ciprofloxacin, levofloxacin, and moxifloxacin) and AEs related to pregnancy, as well as their potential impact on congenital disorders. Methods: A disproportionality analysis was conducted utilizing FDA Adverse Event Reporting System (FAERS) data spanning from the first quarter of 2004 to September 2023. The objective was to identify potential AEs signatures associated with fluoroquinolones through conducting reporting odds ratios (RORs) and Bayesian confidence propagation neural networks (BCPNN). Assessing the potential risk of pregnancy-associated AEs involved comparing each fluoroquinolone with all other medications. Additionally, in-depth comparative analyses were carried out between various fluoroquinolones and a reference drug (azithromycin). Results: A total of 1159 cases were identified, involving AEs related to pregnancy and congenital disorders. Obvious disproportionate association of abortion spontaneous and other nine AEs was identified for fluoroquinolone during gestation. Upon comparison with all the other drugs, ciprofloxacin exhibited an elevated risk of spontaneous abortion, non-site specific bone disorders congenital and 10 other significant signals. Levofloxacin demonstrated an increased risk of congenital tongue disorders and three other significant signals. Moxifloxacin displayed a noteworthy signal indicating multiple congenital cardiac abnormalities. Conclusions: We present compelling evidence regarding pregnancy-related AEs and congenital disorders linked to fluoroquinolones. Considering perinatal and genotoxicity aspects, we explore whether levofloxacin or moxifloxacin might be preferable when fluoroquinolones are deemed necessary to balance the benefits of pregnant women and fetuses.

Effect of Hot Metal Gas Forming Process on Formability and Microstructure of 6063 Aluminum Alloy Double Wave Tube.

The hot metal gas forming process can significantly improve the formability of a tube and is suitable for the manufacturing of parts with complex shapes. In this paper, a double wave tube component is studied. The effects of different temperatures (400 °C, 425 °C, 450 °C and 475 °C) and different pressures (1 MPa, 1.5 MPa, 2 MPa, 2.5 MPa and 3 MPa) on the formability of 6063 aluminum alloy tubes were studied. The influence of hot metal gas forming process parameters on the microstructure was analyzed. The optimal hot metal gas forming process parameters of 6063 aluminum alloy tubes were explored. The results show that the expansion rate increases with the increase in pressure. The pressure affects the deformation of the tube, which in turn has an effect on the dynamic softening of the material. The expansion rate of parts also increases with the increase in forming temperature. The increased deformation temperature is beneficial to the dynamic recrystallization of 6063, resulting in softening of the material and enhanced deformation uniformity between grains, so that the formability of the material is improved. The optimum hot metal gas forming process parameters of 6063 aluminum alloy tubes are the temperature of 475 °C and the pressure of 2.5 MPa; the maximum expansion ratio is 41.6%.

Long noncoding RNA Gm2694 drives depressive-like behaviors in male mice by interacting with GRP78 to disrupt endoplasmic reticulum homeostasis.

Long noncoding RNAs (lncRNAs) are involved in various biological processes and implicated in the regulation of neuronal activity, but the potential role of lncRNAs in depression remains largely unknown. Here, we identified that lncRNA Gm2694 was increased in the medial prefrontal cortex (mPFC) of male mice subjected to chronic social defeat stress (CSDS). The down-regulation of Gm2694 in the mPFC alleviated CSDS-induced depressive-like behaviors through enhanced excitatory synaptic transmission. Furthermore, we found that Gm2694 preferentially interacted with the carboxyl-terminal domain of 78-kilodalton glucose-regulated protein (GRP78), which abrogated GRP78 function and disrupted endoplasmic reticulum homeostasis, resulting in a reduction of the surface expression of AMPA receptors (AMPARs). Overexpression of GRP78 in the mPFC promoted the surface expression of AMPARs and attenuated the CSDS-induced depressive-like behaviors of mice. Together, our results unraveled a previously unknown role of Gm2694 in regulating endoplasmic reticulum homeostasis and excitatory synaptic transmission in depression.

Deficiency of Glycosylated α-Dystroglycan in Ventral Hippocampus Bridges the Destabilization of Gamma-Aminobutyric Acid Type A Receptors With the Depressive-like Behaviors of Male Mice.

BACKGROUND: Depression is a common psychiatric disorder associated with defects in GABAergic (gamma-aminobutyric acidergic) neurotransmission. α-Dystroglycan (α-DG), a cell adhesion molecule known to be essential for skeletal muscle integrity, is also present at inhibitory synapses in the central nervous system and forms a structural element in certain synapses. However, the role of α-DG in the regulation of depressive-like behaviors remains largely unknown. METHODS: Depressive-like behaviors were induced by chronic social defeat stress in adult male mice. Surface protein was extracted by a biotin kit, and the expression of protein was detected by Western blotting. Intrahippocampal microinjection of the lentivirus or adeno-associated virus or agrin intervention was carried out using a stereotaxic instrument and followed by behavioral tests. Miniature inhibitory postsynaptic currents were recorded by whole-cell patch-clamp techniques. RESULTS: The expression of α-DG and glycosylated α-DG in the ventral hippocampus was significantly lower in chronic social defeat stress-susceptible male mice than in control mice, accompanied by a decreased surface expression of GABAA receptor γ2 subunit and reduced GABAergic neurotransmission. RNA interference-mediated knockdown of Dag1 increased the susceptibility of mice to subthreshold stress. Both in vivo administration of agrin and overexpression of like-acetylglucosaminyltransferase ameliorated depressive-like behaviors and restored the decrease in surface expression of GABAA receptor γ2 subunit and the amplitude of miniature inhibitory postsynaptic currents in chronic social defeat stress-exposed mice. CONCLUSIONS: Our findings demonstrate that glycosylated α-DG plays a role in the pathophysiological process of depressive-like behaviors by regulating the surface expression of GABAA receptor γ2 subunit and GABAergic neurotransmission in the ventral hippocampus.

[Risk factors analysis on wound complications after closed calcaneal frature operation using lateral extensive L-shaped incision].

OBJECTIVE: To investigate the risk factors of wound complications after closed calcaneal fracture operation using a lateral extensive L-shaped incision and to explore the effective interventions to reduce the complications after incision. METHODS: Retrospective analysis of clinical data of 285 patients(315 calcaneal fractures) who underwent open reduction and internal fixation by using the lateral extensive L-shaped incision from January 2011 to January 2015. Eighteen factors which might cause the complications of calcaneal incision were compared by univariate analysis, and multiple Logistic regression analysis was performed for factors with statistically significances. RESULTS: Twenty-nine patients(30 calcaneus) had wound complications among all the 285 patients(315 calcaneus) after surgery, including 9 patients with incision redness, swelling, oozing or nonunion;16 patients with skin necrosis or incision rupture, 3 patients with soft tissue superficial infection, and 2 patients with osteomyelitis. Univariate analysis showed that fall height(P=0.017), diabetes (P=0.026), smoking(P=0.001), and operative time(P=0.003) were correlated with incision complications after surgery. Multivariate analysis showed that diabetes(P=0.029), smoking(P<0.001), and operative time(P=0.018) were risk factors for incision complications after operation. CONCLUSIONS: Preoperative smoking cessation, actively control of blood glucose and shortening the operation time by practicing can effectively reduce the incision complication after fracture surgery with the lateral extensive L-shaped incision.

[Applicability Comparison and Application Study of Two Methods for Determination of the Copper Complexing Capacity of Waters].

Complexing capacity (CC) is an important indicator affecting the environmental behavior of heavy metals in water, which can be determined by different methods based on different mechanisms. To validate and compare the applicability of different methods in CC determination, the complexing capacity of Cu2+ (CuCC) in solutions of ethylenediamine tetraacetic acid (EDTA) and acesulfame was determined by methods of dithizone extraction kinetics (DEK) and ion-selective electrodes (ISE), while EDTA and acesulfame were selected to represent strong and weak ligands in water, respectively. DEK method was found to be more suitable for determining the contribution of strong ligands to CuCC, while the results determined by ISE were related to both the strong and weak ligands in water. DEK and ISE methods were used to measure CuCC of several actual water samples, including samples from reservoir, discharge river, fishpond, and landfill leachates. CuCC in the water samples of the reservoir and discharge river measured by ISE were 86.9-227.0 µmol·L-1, which were about one order of magnitude higher than those measured by DEK (9.9-14.6 µmol·L-1). For the landfill leachates, CuCC measured by ISE were 6998.4-31005.8 µmol·L-1, which were 2 orders of magnitude higher than those by DEK (89.6-109.1 µmol·L-1). The increase of CuCC in the polluted water samples might be due to the weak ligands like pollutants. A positive correlation (R=0.975, P<0.01) was found between the CuCC related to the weak ligands (ΔCuCC) and the sum concentration of ammonia nitrogen and organic nitrogen in waters.