Chloroprocaine 3% for anesthesia during cesarean section in a patient with dopa-responsive dystonia: A case report.

RATIONALE: Dopa-responsive dystonia (DRD) is a rare autosomal dominant hereditary disorder with a prevalence of 0.5 per million population. The disease is characterized by onset of dystonia in childhood, progressive aggravation of the dystonia with diurnal fluctuation, and complete or near complete alleviation of symptoms with low-dose oral levodopa. The incidence of DRD is low, and only a few publications have described this disorder connected with anesthesia. PATIENT CONCERNS: We present a case involving a pregnant woman with DRD who continued levodopa/benserazide throughout the pregnancy. The perioperative anesthesia management was described. We used chloroprocaine 3% for epidural anesthesia during cesarean section. DIAGNOSES: Dopa-responsive dystonia. INTERVENTIONS: Levodopa/benserazide. OUTCOMES: In summary, levodopa/benserazide was continued throughout our patient's pregnancy with a good obstetric outcome, and chloroprocaine was safely used in epidural anesthesia without deterioration of her dystonic symptoms. LESSONS: Chloroprocaine was safely used in epidural anesthesia without deterioration of her dystonic symptoms.

Regulation of YAP translocation by myeloid Pten deficiency alleviates acute lung injury via inhibition of oxidative stress and inflammation.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, the myeloid PTEN governing Hippo-YAP pathway mediated oxidative stress and inflammation in lipopolysaccharide (LPS)-induced ALI remains to be elucidate. METHODS: The floxed Pten (PtenFL/FL) and myeloid-specific Pten knockout (PtenM-KO) mice were intratracheal instill LPS (5 mg/kg) to establish ALI, then Yap siRNA mix with the mannose-conjugated polymers was used to knockdown endogenous macrophage YAP in some PtenM-KO mice before LPS challenged. The bone marrow-derived macrophages (BMMs) from PtenFL/FL and PtenM-KO mice were obtained, and BMMs were transfected with CRISPR/Cas9-mediated glycogen synthase kinase 3 Beta (GSK3ß) knockout (KO) or Yes-associated protein (YAP) KO vector subjected to LPS (100 ng/ml) challenged or then cocultured with MLE12 cells. RESULTS: Here, our findings demonstrate that myeloid-specific PTEN deficiency exerts a protective against LPS-induced oxidative stress and inflammation dysregulated in ALI model. Moreover, ablation of the PTEN-YAP axis in macrophages results in reduced nuclear factor-E2-related factor-2 (NRF2) expression, a decrease in antioxidant gene expression, augmented levels of free radicals, lipid and protein peroxidation, heightened generation of pro-inflammatory cytokines, ultimately leading to increased apoptosis in MLE12 cells. Mechanistically, it is noteworthy that the deletion of myeloid PTEN promotes YAP translocation and regulates NRF2 expression, alleviating LPS-induced ALI via the inhibition of GSK3ß and MST1 binding. CONCLUSIONS: Our study underscores the crucial role of the myeloid PTEN-YAP-NRF2 axis in governing oxidative stress and inflammation dysregulated in ALI, indicating its potential as a therapeutic target for ALI.

K+-Specification with Flavone P0 Probe in a G-Quadruplex DNA.

G-quadruplex (G4) DNA is considered as a prospective therapeutic target due to its potential biological significance. To understand G4 biological roles and function, a G4-specific fluorescent probe is necessary. However, it is difficult for versatile G4 to precisely recognize without perturbing their folding dynamics. Herein, we reported that flavone P0 can be a fluorescent probe for G4 DNA-specific recognition and have developed a highly selective detection of K+ ion by dimeric G4/P0 system. When comparing various nucleic acid structures, including G4, i-motif, ss/ds-DNA, and triplex, an apparent fluorescence enhancement is observed in the presence of G4 DNA for 85-fold, but only 8-fold for non-G4 DNA. Furthermore, based on fluorescent probe of flavone P0 for G4 DNA screening, the noncovalent dimeric G4/P0 system is exploited as a K+ sensor, that selectively responds to K+ with a 513-fold fluorescence enhancement and a detection range for K+ ion concentration from 0 to 500 mM. This K+ sensor also has a remarkably anti-interference ability for other metal cations, especially for a high concentration of Na+. These results have demonstrated that flavone P0 is an efficient tool for monitoring G-quadruplex DNA and endows flavone P0 with bioanalytical and medicinal applications.

Efficient Silver(I)-Containing i-Motif DNA Hybrid Catalyst for Enantioselective Diels-Alder Reactions.

The inherent chiral structures of DNA serve as attractive scaffolds to construct DNA hybrid catalysts for valuable enantioselective transformations. Duplex and G-quadruplex DNA-based enantioselective catalysis has made great progress, yet novel design strategies of DNA hybrid catalysts are highly demanding and atomistic analysis of active centers is still challenging. DNA i-motif structures could be finely tuned by different cytosine-cytosine base pairs, providing a new platform to design DNA catalysts. Herein, we found that a human telomeric i-motif DNA containing cytosine-silver(I)-cytosine (C-Ag+-C) base pairs interacting with Cu(II) ions (i-motif DNA(Ag+)/Cu2+) could catalyze Diels-Alder reactions with full conversions and up to 95% enantiomeric excess. As characterized by various physicochemical techniques, the presence of Ag+ is proved to replace the protons in hemiprotonated cytosine-cytosine (C:C+) base pairs and stabilize the DNA i-motif to allow the acceptance of Cu(II) ions. The i-motif DNA(Ag+)/Cu2+ catalyst shows about 8-fold rate acceleration compared with DNA and Cu2+. Based on DNA mutation experiments, thermodynamic studies and density function theory calculations, the catalytic center of Cu(II) ion is proposed to be located in a specific loop region via binding to one nitrogen-7 atom of an unpaired adenine and two phosphate-oxygen atoms from nearby deoxythymidine monophosphate and deoxyadenosine monophosphate, respectively.

Association between healthy eating and depression symptoms among Chinese older adults: A cross-sectional study based on the Chinese Longitudinal Healthy Longevity survey.

Introduction: This study aimed to assess the relationship between the healthy eating index (HEI) and depression symptoms in an older adult population using the Chinese Longevity Health Survey. Methods: The HEI was constructed based on the frequency of intake of 13 dietary variables, with higher scores indicating better diet quality. Depression symptoms was assessed by the Center for Epidemiologic Studies Depression-10 scale. We used multivariate binary logistic regression to explore the association between the HEI and depression symptoms and reported as odds ratio (OR) and 95 % confidence interval (95 % CI). Results: A total of 12,078 older adults were included. The average HEI for this group of older adults was 26.4 ± 7.1. After adjusting for covariates, compared with participants in the lowest quartile of a healthy eating index, those in the second to the fourth quartile group had a 0.93- (95 % CI: 0.83 to 1.03), 0.84- (95 % CI: 0.75 to 0.95) and 0.69- (95 % CI: 0.62 to 0.77) fold risk of depression symptoms, respectively. Restricted cubic spline curves showed that the risk of depression symptoms decreased with increasing HEI, especially above 26, and for each unit increase in the HEI, the risk of depression symptoms in older adults decreased by 3 % (OR = 0.97; 95 % CI: 0.96 to 0.99). Conclusions: This study found an association between higher levels of the HEI and reduced risk of depression symptoms in older Chinese adults. This result emphasizes the need to focus on dietary diversity in older adults to promote healthy aging.

Dopamine oxidation promoted by human telomeric DNA models in the presence of a Cu(II) terpyridine chelate.

We found that under oxidative stress conditions, the coexistence of human telomeric DNA (HT-DNA) and a copper-terpyridine metallodrug can accelerate dopamine oxidation. The unwinding of HT-DNA from a duplex to cytosine-rich (C-rich) and guanine-rich (G-rich) single strands promotes dopamine oxidation in a general order of C-rich > G-rich > duplex. Along with dopamine oxidation, HT-DNA also undergoes severe damage.

Effects of ketamine and esketamine on preventing postpartum depression after cesarean delivery: A meta-analysis.

BACKGROUND: Ketamine and esketamine has been suggested to have potential efficacy in preventing postpartum depression (PPD) recent years. The aim of this meta-analysis was to evaluate the effectiveness of ketamine and esketamine on PPD after cesarean delivery. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for studies investigating the efficacy of ketamine and esketamine in preventing PPD. The primary outcomes of this study were risk ratios (RRs) and EPDS scores (Edinburgh Postnatal Depression Scale) in relation to PPD after ketamine and esketamine. The second outcomes were the postoperative adverse events. RESULTS: Thirteen randomized controlled trials (RCTs) and one retrospective study including 2916 patients were analyzed, including six on the use of ketamine and eight on the use of esketamine. The risk ratios and EPDS scores of PPD were significantly decreased in the ketamine/esketamine group compared to those in the control group in one week and four weeks postoperative periods. Subgroup analyses showed that high dosage, administrated in patient controlled intravenous analgesia (PCIA) method and only esketamine exhibited a significant reduction in the incidence and EPDS scores of PPD in one week and four week postoperative. However, the incidences of postoperative adverse events, such as dizziness, diplopia, hallucination, and headache were significantly higher in the ketamine/esketamine group than that in the control group. CONCLUSION: Ketamine and esketamine appear to be effective in preventing PPD in the one week and four week postoperative periods after cesarean delivery with moderate certainty of evidence. But they can also lead to some short-term complications too. Future high-quality studies are needed to confirm the efficacy of ketamine and esketamine in different countries.

Effect of different intensity exercises on cardiopulmonary function and quality of life of patients with chronic heart failure : A systematic review and meta-analysis.

BACKGROUND: Exercise-based cardiac rehabilitation has positive benefits for patients with chronic heart failure (CHF), but the choice of exercise intensity has been controversial. The aim of this systematic review and meta-analysis was to investigate the effects of different exercise intensities on cardiopulmonary function and quality of life (QoL) of patients with CHF. METHODS: Randomized controlled trials (RCTs) of different exercise intensities applied to patients with CHF were searched in PubMed, Web of Science, the Cochrane Library, and Embase databases from inception to December 2021. Study selection and data extraction were performed simultaneously by two independent reviewers, using the Physiotherapy Evidence Database Scale (PEDro) for quality assessment of the included literature. The weighted mean differences (WMD) or standardized mean difference (SMD) were calculated by employing a fixed or random effects model. Other statistical analyses included subgroup analysis and sensitivity analysis. Quality of evidence was evaluated by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) method. RESULTS: Eight RCTs were included. Analyses reported no significant improvement in left ventricular ejection fractions (LVEF; WMD = 0.47, 95% CI [-4.10, 5.03], p = 0.841), peak oxygen uptake (peak VO2) (SMD = 0.38, 95% CI [-0.03, 0.80], p = 0.069) and 6­min walking distance (6MWD) (WMD = 14.10, 95% CI [-9.51, 37.72], p = 0.242). Exercise interventions of varying intensity produced small-to-moderate beneficial effects on QoL (WMD = -4.99, 95% CI [-8.29, -1.68], p = 0.003), which appeared to be attenuated at long-term follow-up (WMD = 2.12, 95% CI [-2.91, 7.16], p = 0.409). CONCLUSION: High-intensity exercise does not have a significant advantage over moderate-intensity exercise in improving cardiopulmonary function and aerobic capacity in patients with CHF. Beneficial changes in QoL from high-intensity exercise also appeared to decrease during long-term follow-up, indicating a cumulative effect of the efficacy of high-intensity exercise.

Detection Rates of Mental Health Problems Among Sexual Minorities in Mainland China: A Meta-Analysis.

Previous studies that have addressed the growing mental health problems among sexual minorities in mainland China, but failed to inform mental health programs and public health policies with consistent detection results. To obtain robust results on aggregate detection rates and moderators of these problems, we performed a meta-analysis of the related Chinese and English literature published before 2022. Ultimately, 305 eligible studies (ndepression = 127, nanxiety = 71, nsuicide ideation = 55, nsuicide plan = 13, nsuicide attempt = 39) were pooled in the analysis. The results revealed "Money boys" and people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) had higher detection rates than general men who have sex with men. Depression was more prevalent in gays than lesbians, and the latter had a higher detection rate of suicide. Detection rates of anxiety and depression among sexual minorities in China were moderated by detection time, measurement tools, and their detection thresholds. Suggested future priorities include developing more targeted measurement tools that consider the living conditions and psychological characteristics of local sexual minorities, enhancing mental health programs for sexual minorities, and devising more practical and effective interventions to prevent and reduce their mental health problems.

Sexual Minorities within Heterosexuality: Psychosocial Characteristics of and Attitudes toward the "Fourth Love" in China.

Objective: Within the context of gender diversity, the concept of heterosexuality is also changing, emerging as a diversified sexual orientation and identity. This study aims to challenge the orthodoxy about heterosexuality by exploring the psychosocial characteristics and attitudes toward "fourth love" in China. Method: Two studies initially explored the current status of fourth love as a sexual minority. In Study 1, The Sex-Role Inventory and the Marital Attitude Scale were used to assess fourth-love (N = 144) and traditionally heterosexual participants' (N = 145) gender roles and marriage attitudes. In study 2, the Attitudes Toward the Fourth Love Scale was developed to assess college students' (N = 315) attitudes toward fourth-love men and women. Result: Fourth-love women often identify with masculine gender roles and significant differences were found between fourth-love and traditionally heterosexual women their gender roles. Fourth-love men identified with a neutral gender role, while there are significant differences between fourth-love men and traditionally heterosexual women in masculine gender roles. Fourth-love people's marriage attitudes were more negative than those of traditionally heterosexual people, especially for women. Various demographic factors influenced college students' attitudes toward the fourth love. Conclusion: As a sexual minority within the umbrella of heterosexuality in China, fourth-love individuals require further research attention and increased support.

Relationship between CYP2C19 Polymorphism and Clopidogrel Resistance in Patients with Coronary Heart Disease and Ischemic Stroke in China.

Objective: Clopidogrel is widely used for preventing ischemic complications related to cardiovascular diseases. However, many patients experience clopidogrel resistance (CR). The polymorphisms of CYP2C19 have been implicated in CR, but CYP2C19 polymorphism considerably varies with both ethnic group and geographical location. This study aimed to investigate the association between CYP2C19 polymorphisms and clopidogrel resistance (CR) in patients with coronary heart disease and ischemic stroke among Han and Tibetan populations in Qinghai Province, China. Methods: From June 2019 to January 2020, patients who were diagnosed with coronary heart disease or cerebral infarction in internal medicine of Qinghai Provincial People's Hospital and had taken dual antiplatelet drugs were included in this study. Blood was collected and routine items were completed. Whole exome sequencing was performed for CYP2C19 genetic polymorphisms of CYP2C19∗2 (rs4244285), CYP2C19∗3 (rs4986893), and CYP2C19∗17 (rs12248560). Results: A total of 91 patients with coronary heart disease or cerebral infarction (67 Han people (65.99 ± 12.25 years old) and 24 Tibetan (63.6324 Tib years old)) including 52 cases with CR and 39 cases with non-CR were enrolled in this study. For the Han population, the differences in age, glycosylated hemoglobin, activated partial thromboplastin time (APTT), gender, aspirin resistance, and diabetes were significant between the CR and non-CR groups. For the Tibetan population, the two groups showed no significant difference in all indicators. There was no significant difference between CR and non-CR groups for all genotypes (CYP2C19 ∗2, ∗3, and ∗17) in either Han or Tibetan populations. For the Han populations, age, APTT, and aspirin resistance were significantly correlated with CR. Conclusion: The present study indicated that CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 alleles were not correlated with CR for both Han and Tibetan populations in Qinghai Province, while age, APTT, and aspirin resistance were independent risk factors of CR in this region.

The effects of combined spinal-epidural analgesia and epidural anesthesia on maternal intrapartum temperature: a randomized controlled trial.

BACKGROUND: Labor epidural analgesia has been suggested to be associated with intrapartum fever. We designed this study to investigate the effects of epidural analgesia and combined spinal-epidural analgesia on maternal intrapartum temperature. METHODS: Four hundred healthy nullipara patients were randomly assigned to receive either epidural analgesia (EA group) or combined spinal-epidural analgesia (CSEA group). Maternal temperature was measured hourly after analgesia administration. The primary outcome was the incidence of maternal fever, and the secondary outcomes were the duration of analgesia, analgesia to full cervical dilation and analgesia to delivery. Neonatal outcomes and other basic labor events were also recorded. RESULTS: Maternal temperature gradually increased with time in both analgesia groups during labor. However, the CSEA group had a lower incidence of maternal fever, and a lower mean maternal temperature at 5 h, 6 h, and 9 h after analgesia. In addtion, the CSEA group also had a shorter time of analgesia duration, analgesia to full cervical dilation, analgesia to delivery, and less dose of epidural local anesthetic than the EA group. CONCLUSION: Our findings suggest that combined spinal-epidural analgesia is associated with a lower risk of intrapartum fever than epidural analgesia. TRIAL REGISTRATION: ChiCTR1900026606 . Registered on 16/10/2019.

hucMSC-sEVs-Derived 14-3-3ζ Serves as a Bridge between YAP and Autophagy in Diabetic Kidney Disease.

As nanoscale membranous vesicles, human umbilical cord mesenchymal stem cell-derived small extracellular vesicles (hucMSC-sEVs) have attracted extensive attention in the field of tissue regeneration. Under the premise that the mechanisms of hucMSC-sEVs on the treatment of diabetic kidney disease (DKD) have not been revealed clearly, we constructed DKD rat model with success. After tail vein injection, hucMSC-sEVs effectively reduced blood glucose, maintained body weight and improved renal function in DKD rats. Notably, we found that hucMSC-sEVs suppressed YAP expression in renal cortical regions. Further in vitro experiments, we confirmed that the expression of YAP in the nucleus of renal podocytes was increased, and the level of autophagy was inhibited in the high-glucose environment, which could be reversed by intervention with hucMSC-sEVs. We screened out the key protein 14-3-3ζ, which could not only promote YAP cytoplasmic retention instead of entering the nucleus, but also enhance the level of autophagy in the cytoplasm. Ultimately, excessive YAP protein was removed by autophagy, a classic way of protein degradation. In conclusion, our study provides new strategies for the prevention of DKD and proposes the possibility of hucMSC-sEVs becoming a new treatment for DKD in the future.

Repeated Sevoflurane Exposure in Neonatal Rats Enhances the Sensitivity to Pain and Traumatic Stress Later in Juvenile Life.

Purposeː: Sevoflurane exposure in the neonatal period of rodent animals was reported to be associated with neuroendocrine dysregulations later in life. We tested the hypothesis that repeated sevoflurane exposure in neonatal rats enhances the sensitivity to pain and acute traumatic stress response later in juvenile life and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) activity is involved in mediating these abnormalities. Methodsː: The postnatal 6 days (P6) Sprague-Dawley male rat pups pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 2.1% sevoflurane exposure for 2 hours daily in 3 consecutive days. Resultsː: The results showed that repeated exposures to sevoflurane in neonatal rats significantly reduced the paw withdrawal thermal latency (PWTL) at P9, P45. Repeated exposures to sevoflurane in neonatal rats did not significantly affect the basal secretion of serum corticosterone at juvenile period P45, whereas the level of corticosterone for neonatal sevoflurane-exposed rats at P45 was significantly higher than the CON group after subject to conditioned fear traumatic stress (CFTS). The resulting NKCC1/KCC2 mRNA ratio was significantly increased immediately after the neonatal rats received the last sevoflurane exposure, which was alleviated by pretreated with the NKCC1 inhibitor bumetanide. Conclusionː: Repeated exposures to sevoflurane in neonatal rats enhanced the sensitivity to pain and acute traumatic stress response in juvenile life. The neonatal brain depolarizing GABAAR activity is involved in mediating these abnormalities.

Therapeutic effects of exercise interventions for patients with chronic kidney disease: an umbrella review of systematic reviews and meta-analyses.

OBJECTIVE: To conduct an overview of meta-analyses evaluating the impact of exercise interventions on improving health outcomes in patients with chronic kidney disease (CKD). DESIGN: An umbrella review of systematic review and meta-analyses of intervention trials was performed. DATA SOURCES: PubMed, Web of Science, Embase and the Cochrane Database of Systematic Reviews were searched from inception to 9 March 2021 for relevant articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible meta-analyses compared the effects of usual care with and without exercise in patients with CKD. Health outcomes included those related to cardiovascular risk factors, physical fitness, dialysis-related symptoms, dialysis adequacy and health-related quality of life. Systematic reviews and meta-analyses that included fewer than 3 RCTs or fewer than 100 participants were excluded from the analysis. RESULTS: A total of 31 eligible systematic reviews and meta-analyses were included that assessed 120 outcomes. For physical fitness, there was a moderate effect size for cardiorespiratory fitness, muscle strength and body composition and small effect size for muscle endurance. The effect sizes for cardiovascular risk factors, dialysis-related symptoms and health-related quality of life outcomes were small. According to the Grading of Recommendations Assessment, Development and Evaluation framework, most outcomes were low or very low quality. CONCLUSION: Exercise appears to be a safe way to affect concomitant cardiovascular risk factors, such as blood pressure, improve physical fitness and health-related quality of life and reduce dialysis-related symptoms in patients with CKD. PROSPERO REGISTRATION NUMBER: CRD42020223591.

Repeated Sevoflurane Exposures in Neonatal Rats Increased the Brain Vulnerability to Future Stress Exposure and Resulted in Fear Extinction Deficit.

Sevoflurane anesthesia during neonatal period was reported to sensitize the rodent animals to stress later in life. The authors tested the hypothesis that repeated sevoflurane exposures in neonatal rats increased the brain vulnerability to future stress exposure and resulted in fear extinction deficit and investigated whether the neonatal brain depolarizing γ-aminobutyric acid type A receptor (GABAAR) is involved in mediating these abnormalities. Neonatal Sprague-Dawley male rats, pretreated with vehicle or the NKCC1 inhibitor, bumetanide, received sequential exposures to 3% sevoflurane for 2 h on postnatal days (P) 5, P6, and P7 and then were exposed to electric foot shock stress in fear conditioning training at P14. Juvenile rats at different developmental brain stage receiving identical sevoflurane exposures on P25, P26, and P27 were also studied. The results showed repeated sevoflurane exposures in neonatal rats and increased the cation-chloride cotransporters NKCC1/KCC2 ratio in the PFC at P14. Repeated exposures to sevoflurane in neonatal rather than juvenile rats enhanced the stress response and exacerbated neuroapoptosis in the PFC after exposed to electric foot shock in fear conditioning training. Neonatal rather than juvenile sevoflurane-exposed rats exhibited deficits in fear extinction training and recall. Pretreatment of neonatal rats prior to sevoflurane exposures with bumetanide reduced the NKCC1/KCC2 ratio at P14 and ameliorated most of the subsequent adverse effects. Our study indicates that repeated sevoflurane exposures in neonatal rats might increase the brain vulnerability to future stress exposure and resulted in fear extinction deficit, which might be associated with the neonatal enhanced brain depolarizing GABAAR activity.

Participation of Increased Circulating MAIT Cells in Lung Cancer: a Pilot Study.

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells that regulate the immune response via rapidly releasing inflammatory factors, including during progression of some tumors. However, the immunological role of MAIT cells is still unclear in lung cancer. We measured percentage, partial function, and clinical correlation of circulating MAIT cells from lung cancer patients through flow cytometry. Lung cancer patients displayed a high concentration of CD4+, CD8+, and activated CD38+CD8+MAIT cells, and a decrease of PD1+ double negative (DN) MAIT cells in peripheral blood. Meanwhile, increased levels of interferon-γ, interleukin (IL)-6, and 8 were examined in the serum of lung cancer patients. Importantly, we discovered a statistically positive association between accumulation of CD38+CD8+MAIT cells and reduced progression-free survival of lung cancer patients. While preliminary, the altering frequency of MAIT cells might be involved in dysfunctional immune response in lung cancer.