A national-wide survey on clinical implementation of PGx testing into precision therapeutics for Chinese children: a long way before standard clinical practice.

BACKGROUND: Pharmacogenetics/pharmacogenomics (PGx) focuses on the genetic variation that causes the heterogeneity of pharmacokinetics and drug response among individuals and has the potential to predict individual efficacy and/or side effects. This study aims to investigate and understand the implementation of genetic testing for the personalized medication (GTPM) in children's hospitals in Mainland China. METHODS: A survey was conducted on 50 children's hospitals from 31 provinces, municipalities, and autonomous regions across Mainland China, and statistical analysis and recommendations were made. RESULTS: Questionnaire response was rate of 76.0% (38/50). Data from 15 hospitals conducting GTPM were included in this study, but only 6 hospitals had offered PGx tests for no less than five drug-related genes, and only 5 hospitals had covered more than ten drugs, which was a small scale overall. 20.0% of the laboratories did not conduct internal quality control, and 33.3% did not participate in inter-laboratory quality assessment. 46.7% of the practitioners did not receive external training. The primary goal for GTPM was to optimize drug dosage in the 15 hospitals, while the main challenge for GTPM was the implementation cost. CONCLUSION: Although GTPM in pediatrics has made major progress in Mainland China in recent years, there were still various problems in terms of software, hardware configuration, personnel allocation, business scale, quality control, and result interpretation. This requires joint efforts of health administration, medical insurance departments, researchers, and hospitals to promote and improve GTPM.

[Risk factors for initial non-invasive ventilation failure in very low birth weight infants with gestational age <32 weeks: a multicenter retrospective study]. / 胎龄<32å‘¨æžä½Žå‡ºç”Ÿä½“é‡å„¿åˆå§‹æ— åˆ›é€šæ°”å¤±è´¥çš„å½±å“å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation (NIV) failure in very low birth weight infants (VLBWI) with gestational age <32 weeks. METHODS: A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit (NICU) in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted. Based on the outcomes of initial NIV, the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis. RESULTS: A total of 817 infants were included, with 453 males (55.4%) and 139 failures (17.0%). The failure group had lower gestational age, birth weight, and 1-minute and 5-minute Apgar scores compared to the successful group (P<0.05). The failure group also had a higher proportion of respiratory distress syndrome (RDS) diagnosed upon NICU admission, higher maximum positive end-expiratory pressure during NIV, and higher percentages of reaching the required maximum fraction of inspired oxygen (FiO2) ≥30%, ≥35%, and ≥40% throughout the initial NIV process compared to the successful group (P<0.05). Gestational age (OR=0.671, 95%CI: 0.581-0.772), RDS (OR=1.955, 95%CI: 1.181-3.366), and FiO2 ≥30% (OR=2.053, 95%CI: 1.106-4.044) were identified as risk factors for initial NIV failure in these infants with gestational age <32 weeks (P<0.05). The failure group had higher incidences of complications such as pulmonary infections, pneumothorax, retinopathy of prematurity, moderate to severe bronchopulmonary dysplasia, and severe intraventricular hemorrhage during hospitalization, as well as longer hospital stays and higher total costs compared to the successful group (P<0.05). CONCLUSIONS: Smaller gestational age, a diagnosis of RDS in the NICU, and achieving a maximum FiO2 ≥30% during the initial NIV process are risk factors for initial NIV failure in infants with gestational age <32 weeks. Initial NIV failure significantly increases the risk of adverse outcomes in this population.

Effects of ultrasonic degradation on physicochemical and antioxidant properties of Gleditsia sinensis seed polysaccharides.

In this study, two degraded polysaccharides from Gleditsia sinensis seed were obtained under ultrasonic power treatments of 300 and 450 W. The physicochemical properties, structural characteristics, and antioxidant activities of the degraded and undegraded polysaccharides were studied and compared. Ion exchange chromatography and methylation analysis showed that the polysaccharides had similar basic structural features and were composed of the same monosaccharide units before and after degradation, but the ultrasonic treatment increased the total monosaccharide content and changed the Mannose/Galactose value. Furthermore, with the increase in the ultrasonic power, the molecular weight and intrinsic viscosity of polysaccharides decreased, and the micromorphology became looser. The scavenging capacities for 1,1-diphenyl-2-picrylhydrazyl and hydroxyl free radicals and the reducing ability were significantly increased by the ultrasonic treatment. In conclusion, ultrasonic treatment may be an effective way to improve the antioxidant activities of polysaccharides from G. sinensis seed, and further studies on its antioxidant mechanism are still needed.

Advancements in Cardiovascular Disease Research Affected by Smoking.

The harmful substances in tobacco are widely recognized to exert a significant detrimental impact on human health, constituting one of the most substantial global public health threats to date. Tobacco usage also ranks among the principal contributors to cardiovascular ailments, with tobacco being attributed to up to 30% of cardiovascular disease-related deaths in various countries. Cardiovascular disease is influenced by many kinds of pathogenic factors, among them, tobacco usage has led to an increased year by year incidence of cardiovascular disease. Exploring the influencing factors of harmful substances in tobacco and achieving early prevention are important means to reduce the incidence of cardiovascular diseases and maintain health. This article provides a comprehensive review of the effects of smoking on health and cardiovascular diseases.

A vascular endothelial growth factor-loaded chitosanhyaluronic acid hydrogel scaffold enhances the therapeutic effect of adipose-derived stem cells in the context of stroke.

Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

Exendin-4 intervention attenuates atherosclerosis severity by modulating myeloid-derived suppressor cells and inflammatory cytokines in ApoE-/- mice.

OBJECTIVE: To investigate the impact of the glucagon-like peptide-1 (GLP-1) receptor agonist Exendin-4 on the proportion of myeloid-derived suppressor cells (MDSCs) in male ApoE-/- mice, and investigate alterations in the concentrations of inflammatory factors in plasma and spleen tissues and assess their correlation with MDSCs. METHODS: Thirty male ApoE-/- mice were randomly divided into five groups (n = 6 per group): control group (CON), model group (MOD), Exendin-4 intervention group (MOD/Ex-4), Exendin-9-39 intervention group (MOD/Ex-9-39), and Exendin-4 + Exendin-9-39 combined intervention group (MOD/Ex-4 + Ex-9-39). After 4 weeks of drug intervention, changes in aortic plaque were observed using Oil Red O staining and H&E staining. Flow cytometry was employed to detect the content of myeloid-derived suppressor cells (MDSCs) in bone marrow and peripheral blood. ELISA was utilized to measure the concentrations of inflammatory factors in mouse peripheral blood plasma, while RT-qPCR was employed to quantify the expression levels of inflammatory factors in the spleen. Pearson correlation analysis was conducted to assess the relationship between MDSCs and inflammatory factors. RESULTS: Mice in the MOD group had significantly higher body weight compared to the CON group, with a statistically significant difference (P<0.05). Following Exendin-4 intervention, body weight was reduced compared to the MOD group (P<0.05). Additionally, Exendin-4 treatment led to a significant reduction in atherosclerotic plaque compared to the MOD group (P<0.001). After Exendin-4 intervention, the proportion of MDSCs in the bone marrow was higher than in the MOD group (P<0.001), and the proportion of MDSCs in peripheral blood was significantly higher than in the MOD group (P<0.05). Further investigation revealed that Exendin-4 could regulate lipid levels in mice, decreasing concentrations of TG (P<0.01), TC (P<0.0001), and LDL-C (P<0.0001), while increasing HDL-C concentrations (P<0.01). Moreover, after Exendin-4 treatment, the level of the cytokine IL-6 in peripheral plasma was significantly lower compared to the MOD group (P<0.0001), while levels of IL-10 and TGF-ß were significantly higher compared to the MOD group (P<0.0001). In the spleen, levels of the cytokines IL-10 (P<0.0001) and TGF-ß (P<0.001) were significantly increased compared to the MOD group. Pearson correlation analysis showed that the proportion of MDSCs in peripheral blood was positively correlated with IL-10 and TGF-ß levels in both the spleen and peripheral blood. Additionally, the proportion of MDSCs in the bone marrow was positively correlated with IL-10 and TGF-ß levels in the spleen and peripheral blood. CONCLUSION: Exendin-4 alleviates the severity of atherosclerosis. This process may be achieved by promoting the secretion of myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood of atherosclerotic ApoE-/- mice, regulating the ratio of inflammatory factors in the body, reducing mouse body weight, and lowering blood lipids.

Preliminary study on the mechanism of SAHA in the treatment of refractory epilepsy induced by GABRG2(F343L) mutation.

Mutations in the γ-amino butyric acid type A (GABAA) receptor γ2 subunit gene, GABRG2, have been associated with refractory epilepsy. Increasing evidence indicates that suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone acetyltransferases (HDACs) inhibitor, can inhibit seizure onset. However, the mechanisms involved remains unknown. The present study aimed to explore the anti-epileptic effect and underlying mechanisms of SAHA in the treatment of refractory epilepsy induced by GABRG2 mutation. In the zebrafish line expressing human mutant GABRG2(F343L), Tg(hGABRG2F343L), SAHA was found to reduce seizure onset, swimming activity, and neuronal activity. In both Tg(hGABRG2F343L) zebrafish and HEK293T cells transfected with GABAA receptor subunits, SAHA could improve the pan-acetylation level and reduce the expression of HDAC1/10. The decreased expressions of GABAA receptor subunits could be rescued by SAHA treatment both in vivo and in vitro, which might be the result of increased gene transcription and protein trafficking. The up-regulated acetylation of histone H3 and H4 as well as Bip expression might be involved in the process. Taken together, our data proved that both histone and non-histone acetylation might contribute to the anti-epileptic effect of SAHA in refractory epilepsy caused by GABRG2(F343L) mutation, demonstrating SAHA as a promising therapeutic agent for refractory epilepsy.

Injectable bone cement cannulated pedicle screw for lumbar degenerative disease in osteoporosis - clinical follow-up of over 5 years.

OBJECTIVE: The aim of this study is to evaluate the clinical efficacy of injectable cemented hollow pedicle screw (CICPS) in the treatment of osteoporotic lumbar degenerative diseases through a large sample long-term follow-up study. Additionally, we aim to explore the risk factors affecting interbody fusion. METHODS: A total of 98 patients who underwent CICPS for transforaminal lumbar interbody fusion (TLIF) for osteoporotic lumbar degenerative disease from March 2011 to September 2017 were analyzed. X-ray and electronic computed tomography (CT) imaging data were collected during preoperative, postoperative, and follow-up periods. The data included changes in intervertebral space height (ΔH), screw failure, cement leakage (CL), and intervertebral fusion. The patients were divided into two groups based on their fusion status one year after surgery: satisfied group A and dissatisfied group B. Surgical data such as operation time, intraoperative bleeding volume and surgical complications were recorded, and visual analog scale (VAS) and Oswestry disability index (ODI) were used to evaluate the improvement of lumbar and leg pain. RESULTS: The mean follow-up time was 101.29 months (ranging from 70 to 128 months). A total of 320 CICPS were used, with 26 screws (8.13%) leaking, 3 screws (0.94%) experiencing cement augmentation failure, and 1 screw (0.31%) becoming loose and breaking. The remaining screws were not loose or pulled out. Female gender, decreased bone density, and CL were identified as risk factors affecting interbody fusion (P < 0.05). Early realization of interbody fusion can effectively prevent the loss of intervertebral space height (P < 0.05) and maintain the surgical treatment effect. Both VAS and ODI scores showed significant improvement during the follow-up period (P < 0.05). Binary logistic regression analysis revealed that decreased bone density and cement leakage were risk factors for prolonged interbody fusion. CONCLUSIONS: The results of long-term follow-up indicate that PMMA enhanced CICPS has unique advantages in achieving good clinical efficacy in the treatment of osteoporosis lumbar degenerative diseases. Attention should be paid to identify female gender, severe osteoporosis, and CL as risk factors affecting interbody fusion.

SIRT3 facilitates mitochondrial structural repair and functional recovery in rats after ischemic stroke by promoting OPA1 expression and activity.

BACKGROUND: Optical atrophy 1 (OPA1), a protein accountable for mitochondrial fusion, facilitates the restoration of mitochondrial structure and function following cerebral ischemia/reperfusion (I/R) injury. The OPA1-conferred mitochondrial protection involves its expression and activity, which can be improved by SIRT3 in non-cerebral ischemia. Nevertheless, it remains obscure whether SIRT3 enhances the expression and activity of OPA1 after cerebral I/R injury. METHODS: Mature male Sprague Dawley rats were intracranially injected with adeno-associated viral-Sirtuin-3(AAV-SIRT3) and AAV-sh_OPA1, followed by a 90-min temporary blockage of the middle cerebral artery and subsequent restoration of blood flow. Cultured cortical neurons of rats were transfected with LV-SIRT3 or LV-sh_OPA1 before a 2-h oxygen-glucose deprivation and reoxygenation. The rats and neurons were subsequently treated with a selective OPA1 activity inhibitor (MYLS22). The interaction between SIRT3 and OPA1 was assessed by molecular dynamics simulation technology and co-immunoprecipitation. The expression, function, and specific protective mechanism of SIRT3 were examined by various analyses. RESULTS: SIRT3 interacted with OPA1 in the rat cerebral cortex before and after cerebral I/R. After cerebral I/R damage, SIRT3 upregulation increased the OPA1 expression, which enhanced deacetylation and OPA1 activity, thus alleviating cerebral infarct volume, neuronal apoptosis, oxidative pressure, and impairment in mitochondrial energy production; SIRT3 upregulation also improved neuromotor performance, repaired mitochondrial ultrastructure and membrane composition, and promoted the mitochondrial biogenesis. These neuroprotective effects were partly reversed by OPA1 expression interference and OPA1 activity inhibitor MYLS22. CONCLUSION: In rats, SIRT3 enhances the expression and activity of OPA1, facilitating the repair of mitochondrial structure and functional recovery following cerebral I/R injury. These findings highlight that regulating SIRT3 may be a promising therapeutic strategy for ischemic stroke.

In-Situ Self-Assembly Dipole Shielding Layer Toward Efficient and Stable Inorganic Perovskite Solar Cells.

Despite CsPbI2.75Br0.25 inorganic perovskites exhibit high potential for single-junction and/or tandem solar cells, unexpected non-radiative recombination, and mismatched interfacial band alignment within the inorganic perovskite solar cells (PSCs) disadvantageously affect their photovoltaic performance. Rational design of the dipole shielding layer (DSL) is vital to realize a win-win situation for the defect passivation and band alignment. Herein, A-site dipole molecules, that is, neopentylamine and 2-methylbutylamine, are employed for in-situ self-assembly of a thus-far unreported DSL at the interface between 3D perovskite and hole transport layer. The as-prepared DSL demonstrates a 2D RP phase perovskite and the lattice-matching structurally-stable DSL@3D perovskite enables to alleviate the unexpected surface defects and suppress the spontaneous non-radiative recombination by means of effectively tuning the surface work function via regulating the dipole moment length and Van der Waals gap. Accordingly, the top dipole-modified inorganic PSCs exhibit a champion power conversion efficiency (PSC) as high as 19.77% and a fill factor over 83%. Equally importantly, the corresponding solar cells demonstrate a remarkable enhanced stability, maintaining 90% of its initial efficiency for more than 1200 h without encapsulation under a 20% ± 5% relative humidity.

SIRT1 restores mitochondrial structure and function in rats by activating SIRT3 after cerebral ischemia/reperfusion injury.

Mitochondrial dysfunction contributes to cerebral ischemia-reperfusion (CI/R) injury, which can be ameliorated by Sirtuin-3 (SIRT3). Under stress conditions, the SIRT3-promoted mitochondrial functional recovery depends on both its activity and expression. However, the approach to enhance SIRT3 activity after CI/R injury remains unelucidated. In this study, Sprague-Dawley (SD) rats were intracranially injected with either adeno-associated viral Sirtuin-1 (AAV-SIRT1) or AAV-sh_SIRT1 before undergoing transient middle cerebral artery occlusion (tMCAO). Primary cortical neurons were cultured and transfected with lentiviral SIRT1 (LV-SIRT1) and LV-sh_SIRT1 respectively before oxygen-glucose deprivation/reoxygenation (OGD/R). Afterwards, rats and neurons were respectively treated with a selective SIRT3 inhibitor, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). The expression, function, and related mechanism of SIRT1 were investigated by Western Blot, flow cytometry, immunofluorescence staining, etc. After CI/R injury, SIRT1 expression decreased in vivo and in vitro. The simulation and immune-analyses reported strong interaction between SIRT1 and SIRT3 in the cerebral mitochondria before and after CI/R. SIRT1 overexpression enhanced SIRT3 activity by increasing the deacetylation of SIRT3, which ameliorated CI/R-induced cerebral infarction, neuronal apoptosis, oxidative stress, neurological and motor dysfunction, and mitochondrial respiratory chain dysfunction, promoted mitochondrial biogenesis, and retained mitochondrial integrity and mitochondrial morphology. Meanwhile, SIRT1 overexpression alleviated OGD/R-induced neuronal death and mitochondrial bioenergetic deficits. These effects were reversed by AAV-sh_SIRT1 and the neuroprotective effects of SIRT1 were partially offset by 3-TYP. These results suggest that SIRT1 restores the structure and function of mitochondria by activating SIRT3, offering neuroprotection against CI/R injury, which signifies a potential approach for the clinical management of cerebral ischemia.

Self-injection-locked thin-film regenerative laser amplifier.

Organic lasers based on distributed feedback (DFB) microcavities have been extensively investigated. However, the application of these lasers is limited by their low output power and large beam divergence. Therefore, laser amplifiers are needed to achieve practically applicable laser intensity and controllable lasing modes for far-field applications. In this work, we report self-injection-locked laser amplifiers using the combination of a DFB microcavity and a Bragg reflector, where a high-reflection mirror acts as the Bragg reflector and its feedback supplies the external-cavity injection. The coherent coupling between the DFB microcavity and the Bragg amplifier is crucial for achieving high conversion efficiency and high-contrast transverse modes. An amplification factor larger than 20 and a single output laser spot with high contrast that has been achieved. Such an integration design of the self-injected DFB microcavity amplifier can be directly utilized in the realization of high-performance thin-film laser sources for practical applications.

Efficacy of different doses of corticosteroids in treating severe COVID-19 pneumonia.

BACKGROUND: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. RESULTS: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8-16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. CONCLUSION: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.

Corrigendum: Persistent activation of autophagy after cisplatin nephrotoxicity promotes renal fibrosis and chronic kidney disease.

[This corrects the article DOI: 10.3389/fphar.2022.918732.].

Distribution and characteristics of bacteria on the hand during oropharyngeal swab collection: Which handwashing points are affected?

AIMS: To identify the contaminated areas of the hand collection and analyse the distribution characteristics of bacteria in the hand after swab collection. DESIGN: This study used a cross-sectional design. METHODS: A cross-sectional study sampling 50 pairs of hands (sampling hand and auxiliary hand) of healthcare workers was performed. Ten samples were collected from each participant. The optimal hand hygiene rates and bacterial colony counts of the whole hand and different hand sections without hand hygiene were identified as the primary outcomes. RESULTS: The optimal hand hygiene rates of the sampling hand and auxiliary hand were 88.8% (222/250) and 91.6% (229/250), respectively. The lowest optimal hand hygiene rates for the sampling hand and the auxiliary hand were both on the dorsal side of the finger and the dorsum of the hand (86.0%, 86.0% vs. 90.0%, 86.0%); the optimal hand hygiene rates for both sites of the sampling hand were 86.0% (43/50), and the optimal hand hygiene rates for the auxiliary hand were 90.0% (45/50) and 86.0% (43/50). The bacteria colony counts did not differ between the sampling hands and auxiliary hand. CONCLUSIONS: The dorsal side of the finger and dorsum of the hand were the most likely to be contaminated during oropharyngeal swab collection. Therefore, it is essential to pay extra attention to hand hygiene care of these two sites during the collection process to minimize the risk of cross-contamination. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were adopted in this study.

Ligand-free Pd-catalyzed highly selective arylation of activated and unactivated alkenes via oxidative and reductive heck coupling.

In this work, an eco-friendly, green, efficient approach for oxidative and reductive Heck-Mizoroki (HM) reactions was developed, which offered acceptable yields from first-pass experiments. Mono-arylation was achieved without the use of ligands, directing groups, or prefunctionalized alkenes. Considering mild reaction conditions, good functional group compatibility, and great regioselectivity, the method can find broad applications in novel medicine and material development and discovery processes.

Corrigendum: Moderate-to-high risk of obstructive sleep apnea with excessive daytime sleepiness is associated with postoperative neurocognitive disorders: a prospective one-year follow-up cohort study.

[This corrects the article DOI: 10.3389/fnins.2023.1161279.].

Effect of fear of hypoglycaemia on sleep quality of patients with type 2 mellitus diabetes: The mediating role of alexithymia.

Background: Patients with type 2 diabetes mellitus (T2DM) commonly experience poor sleep quality. This study aimed to investigate whether alexithymia mediates the association between fear of hypoglycaemia (FoH) and sleep quality in patients with T2DM. Methods: From September 2021 to November 2021, a cross-sectional survey was conducted on 407 patients with T2DM in China. Data collection was made possible through the administration of the Chinese Version of the Worry Scale, Toronto Alexithymia Scale and Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Multiple linear regression analyses were also performed. Results: A total of 65.6% of the participants were male, and 75.7% were aged 18-40 years. FoH showed a moderate and positive correlation with CPSQI scores (r = 0.308, p < 0.001). Alexithymia was weakly and positively correlated with CPSQI scores (r = 0.185, p < 0.001). Meanwhile, FoH exhibited a moderate and positive correlation with alexithymia (r = 0.422, p < 0.001), and difficulty in identifying (r = 0.414, p < 0.001) and describing feelings (r = 0.416, p < 0.001) and a weak and positive correlation with externally oriented thinking (r = 0.221, p < 0.001). The total effect (ß = 0.408, p < 0.001) of FoH on CPSQI comprised not only the direct (ß = 0.293, 95% confidence interval: 0.174-0.411, p < 0.001) but also the indirect effect (ß = 0.115, p < 0.001) of alexithymia. Conclusions: Alexithymia can mediate the association between FoH and sleep quality. Clinicians should recognize the potential effect of alexithymia and incorporate it in intervention planning and care. Addressing the affective disturbances arising from FoH can enhance emotional expression and sleep quality among T2DM patients.

Differential inflammation responses determine the variable phenotypes of epilepsy induced by GABRG2 mutations.

OBJECTIVE: To explore the mechanism involved in variable phenotypes of epilepsy models induced by γ-aminobutyric acid type A γ2 subunit (GABRG2) mutations. METHODS: The zebrafish carrying wild-type (WT) GABRG2, mutant GABRG2(P282S), GABRG2(F343L) and GABRG2(I107T) were established by Tol2kit transgenesis system and Gateway method. Behavioral analysis of different transgenic zebrafish was performed with the DanioVision Video-Track framework and the brain activity was analyzed by field potential recording with MD3000 Bio-signal Acquisition and Processing System. The transcriptome analysis was applied to detect the underlying mechanisms of variable phenotypes caused by different GABRG2 mutations. RESULTS: The established Tg(hGABRG2P282S ) zebrafish showed hyperactivity and spontaneous seizures, which were more sensitive to chemical and physical epileptic stimulations. Traditional antiepileptic drugs, such as Clonazepam (CBZ) and valproic acid (VPA), could ameliorate the hyperactivity in Tg(hGABRG2P282S ) zebrafish. The metabolic pathway was significantly changed in the brain transcriptome of Tg(hGABRG2P282S ) zebrafish. In addition, the behavioral activity, production of pro-inflammatory factors, and activation of the IL-2 receptor signal pathway varied among the three mutant zebrafish lines. CONCLUSION: We successfully established transgenic zebrafish epileptic models expressing human mutant GABRG2(P282S), in which CBZ and VPA showed antiepileptic effects. Differential inflammatory responses, especially the SOCS/JAK/STAT signaling pathway, might be related to the phenotypes of genetic epilepsy induced by GABRG2 mutations. Further study will expand the pathological mechanisms of genetic epilepsies and provide a theoretical basis for searching for effective drug treatment.

Cobalt-Catalyzed Enantioselective Reductive α-Chloro-Carbonyl Addition of Ketimine to Construct the ß-Tertiary Amino Acid Analogues.

ß-Tertiary amino acid derivatives constitute one of the most frequently occurring units in natural products and bioactive molecules. However, the efficient asymmetric synthesis of this motif still remains a significant challenge. Herein, we disclose a cobalt-catalyzed enantioselective reductive addition reaction of ketimine using α-chloro carbonyl compound as a radical precursor, providing expedient access to a diverse array of enantioenriched ß-quaternary amino acid analogues. This protocol exhibits outstanding enantioselectivity and broad substrate scope with excellent functional group tolerance. Preliminary mechanism studies rule out the possibility of Reformatsky-type addition and confirm the involvement of radical species in stereoselective addition process. The synthetic utility has been demonstrated through the rapid assembly of iterative amino acid units and oligopeptide, showcasing its versatile platform for late-stage modification of drug candidates.