Association between BMI and age at menarche or spermarche among both sexes: Findings from six successive national surveys in China.

Background: To explore trends of the association between body mass index (BMI) and age at menarche or spermarche and its urban-rural disparities from 1995 to 2019. Methods: A total of 912 753 children and adolescents - including 519 940 9-18 years old girls and 392 813 11-18 years old boys - were involved in six successive cross-sectional surveys conducted across 30 provinces in China from 1995 to 2019. Data on menarche and spermarche was collected using the status quo method, where same-gender physicians conducted face-to-face interviews to determine if children and adolescents had experienced their first menstrual cycle or ejaculation (yes/no). The median age at menarche or spermarche was estimated by probit analysis. Anthropometric measurements measured the height and weight of the study subjects. Children and adolescents were classified into thinness, normal range of weight, overweight, and obesity. t test was used to compare the differences in BMI between premenarchal and postmenarchal girls or prespermarcheal and postspermarcheal boys. Logistic regression was used to explore the associations between BMI/nutritional status and menarche or spermarche stratified by urban or rural residency status. Results: From 1995 to 2019, BMI in all age groups growth over time, and the values of BMI among children and adolescents under 15 who had menarche or spermarche were more significant than those without menarche or spermarche. In 2019, for girls, thinness was associated with delayed menarche (odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.24-0.28), while overweight (OR = 1.99; 95% CI = 1.85-2.14) and obesity (OR = 2.20; 95% CI = 1.92-2.53) was associated with advanced menarche. For boys, thinness was associated with delayed spermarche (OR = 0.71; 95% CI = 0.65-0.78), overweight was associated with advanced spermarche (OR = 1.08; 95% CI = 1.01-1.15) while obesity had no association with spermarche. The OR between BMI and menarche in 1995 was 1.35 (95% CI = 1.33-1.37), which decreased to 1.19 (95% CI = 1.18-1.20) by 2019. The OR between BMI and spermarche in 1995 was 1.10 (95% CI = 1.09-1.11), which decreased to 1.02 (95% CI = 1.02-1.03) by 2019. The trends by urban-rural stratification were consistent with the total sample. Conclusions: We have established a dose-response relationship between BMI and menarche in girls, whereas the association appears to be nonlinear in boys, and the associations were diminishing. Similar findings were observed in both urban and rural areas. Considering the dual adverse effects of obesity and early puberty on health, the results of this study suggest that sexual health education should be strengthened, especially among obese girls. Further research on the influencing factors and biological mechanisms of early puberty will be beneficial.

Opioid-Free Anesthesia for Pain Relief After Laparoscopic Cholecystectomy: A Prospective Randomized Controlled Trial.

Purpose: To compare the efficacies of opioid-free anesthesia (OFA) and opioid-based anesthesia (OBA) in laparoscopic cholecystectomy (LC). Patients and Methods: A total of 150 patients who underwent 3-port LC procedures were randomly divided into an OFA group with esketamine, dexmedetomidine and lidocaine intravenous combined with local anesthetic incision infiltration or an OBA group with remifentanil combined with local anesthetic incision infiltration. The primary outcome was the consumption of rescue analgesics within 24 hrs after surgery. Secondary outcomes included time to LMA removal, time to orientation recovery, time to unassisted walking, sleep quality on the night of surgery, time to first flatus, hemodynamics during induction of general anesthesia, postoperative pain level on the visual analog scale (VAS), incidence of postoperative nausea and vomiting (PONV) and global satisfaction score (GSS) within 24 hrs after surgery. Results: Both the consumption of rescue analgesics and the time to first flatus in the OFA group were significantly lower than those in the OBA group (P < 0.001 and P = 0.029, respectively). However, the time to LMA removal and the time to orientation recovery were significantly longer in the OFA group than in the OBA group (P < 0.001). In addition, the VAS scores at 2 hrs and 8 hrs after surgery and HR at laryngeal mask airway insertion in the OFA group were significantly lower than those in the OBA group (P = 0.002 and P = 0.001, and P =0.016, respectively). Conclusion: OFA may be beneficial for patients undergoing LC in that it could decrease the dosage of postoperative analgesics and pain intensity and even shorten the time to first flatus after surgery.

Post-genomic era in agriculture and veterinary science: successful and proposed application of genetic targeting technologies.

Gene editing tools have become an indispensable part of research into the fundamental aspects of cell biology. With a vast body of literature having been generated based on next generation sequencing technologies, keeping track of this ever-growing body of information remains challenging. This necessitates the translation of genomic data into tangible applications. In order to address this objective, the generated Next Generation Sequencing (NGS) data forms the basis for targeted genome editing strategies, employing known enzymes of various cellular machinery, in generating organisms with specifically selected phenotypes. This review focuses primarily on CRISPR/Cas9 technology in the context of its advantages over Zinc finger proteins (ZNF) and Transcription activator-like effector nucleases (TALEN) and meganucleases mutagenesis strategies, for use in agricultural and veterinary applications. This review will describe the application of CRISPR/Cas9 in creating modified organisms with custom-made properties, without the undesired non-targeted effects associated with virus vector vaccines and bioactive molecules produced in bacterial systems. Examples of the successful and unsuccessful applications of this technology to plants, animals and microorganisms are provided, as well as an in-depth look into possible future trends and applications in vaccine development, disease resistance and enhanced phenotypic traits will be discussed.

Effect of a Local Anesthetic Injection Kit on Pain Relief and Postoperative Recovery After Transumbilical Single-Incision Laparoscopic Cholecystectomy.

Purpose: This study was conducted to explore whether incisional infiltration using a local anesthetic injection kit could better relieve postoperative pain and enhance the quality of recovery compared with ultrasound-guided rectus sheath block (RSB) or conventional local anesthetic infiltration in patients undergoing transumbilical single-incision laparoscopic cholecystectomy (SILC). Patients and Methods: A total of 60 patients undergoing SILC with American Society of Anesthesiology functional status scores of I-II were randomized into the rectus sheath block group (RSB group), conventional local wound infiltration group (LAI-I group) and incisional infiltration using a local anesthetic injection kit group (LAI-II group). The primary outcomes were the patient-controlled intravenous analgesia (PCIA) demand frequency within 48 hours after the operation and postoperative pain measured by a visual analog scale (VAS) at 2 h, 4 h, 8 h, 24 h, and 48 h after surgery. Secondary outcomes were the total procedure times, cumulative consumption of anesthetic drugs, duration of surgery, duration and awaking time of anesthesia, early recovery indicator and side effects. Results: The PCIA demand frequency in LAI-II group was significantly lower compared with patients in the RSB and LAI-I group (both P < 0.001). Moreover, the total procedure times in LAI-I and LAI-II group was significantly shorter than that in the RSB group (P < 0.001, respectively), but it was comparable between LAI-I and LAI-II group (P = 0.471). Though lower at 2h and 4h postoperative in LAI-II group, pain scores at each time point had no statistical differences among three groups. There were no significant differences among three groups for other outcomes as well. Conclusion: The effect of ultrasound-guided RSB and conventional local anesthetic infiltration in SILC patients were found to be similar in terms of relieving postoperative pain and promoting recovery. Incisional infiltration using a local anesthetic injection kit can significantly reduce the demand frequency of PCIA, which serves as a rescue analgesic.

Effect of Different Administration Routes of Dexmedetomidine on Postoperative Delirium in Elderly Patients Undergoing Elective Spinal Surgery: A Prospective Randomized Double-Blinded Controlled Trial.

BACKGROUND: Intravenous dexmedetomidine has been reported to decrease the occurrence of postoperative delirium (POD) in elderly patients. Nevertheless, some previous studies have indicated that intratracheal dexmedetomidine and intranasal dexmedetomidine are also effective and convenient. The current study aimed to compare the effect of different administration routes of dexmedetomidine on POD in elderly patients. METHODS: We randomly allocated 150 patients (aged 60 years or more) scheduled for spinal surgery to receive intravenous dexmedetomidine (0.6 µg/kg), intranasal dexmedetomidine (1 µg/kg) before anesthesia induction, or intratracheal dexmedetomidine (0.6 µg/kg) after anesthesia induction. The primary outcome was the frequency of delirium during the first 3 postoperative days. The secondary outcomes were the incidence of postoperative sore throat (POST) and sleep quality. Adverse events were recorded, and routine treatment was performed. RESULTS: Compared with the intranasal group, the intravenous group had a significantly lower occurrence of POD within 3 days (3 of 49 [6.1%] vs 14 of 50 [28.0%]; odds ratio [OR], 0.17; 95% confidence intervals [CIs], 0.05-0.63; P < .017). Meanwhile, patients in the intratracheal group had a lower incidence of POD than those in the intranasal group (5 of 49 [10.2%] vs 14 of 50 [28.0%]; OR, 0.29; 95% CI, 0.10-0.89; P < .017). Whereas, there was no difference between the intratracheal and intravenous groups (5 of 49 [10.2%] vs 3 of 49 [6.1%]; OR, 1.74; 95% CI, 0.40-7.73; P > .017). The rate of POST was lower in the intratracheal group than that in the other 2 groups at 2 hours after surgery (7 of 49 [14.3%] vs 12 of 49 [24.5%] vs 18 of 50 [36.0%], P < .017, respectively). Intravenous dexmedetomidine had the lowest Pittsburgh Sleep Quality Index score on the second morning after surgery (median [interquartile range {IQR}]: 4 [3-5] vs 6 [4-7] vs 6 [4-7], P < .017, respectively). Compared with the intranasal group, the intravenous group had a higher rate of bradycardia and a lower incidence of postoperative nausea and vomiting ( P < .017). The intranasal group was associated with the highest incidence of hypertension ( P < .017). CONCLUSIONS: For patients aged ≥60 years undergoing spinal surgery, compared with the intranasal route of dexmedetomidine, intravenous and intratracheal dexmedetomidine reduced the incidence of early POD. Meanwhile, intravenous dexmedetomidine was associated with better sleep quality after surgery, and intratracheal dexmedetomidine resulted in a lower incidence of POST. Adverse events were mild in all 3 administration routes of dexmedetomidine.

Up-regulation of HCN2 channels in a thalamocortical circuit mediates allodynia in mice.

Chronic pain is a significant problem that afflicts individuals and society, and for which the current clinical treatment is inadequate. In addition, the neural circuit and molecular mechanisms subserving chronic pain remain largely uncharacterized. Herein we identified enhanced activity of a glutamatergic neuronal circuit that encompasses projections from the ventral posterolateral nucleus (VPLGlu) to the glutamatergic neurons of the hindlimb primary somatosensory cortex (S1HLGlu), driving allodynia in mouse models of chronic pain. Optogenetic inhibition of this VPLGlu→S1HLGlu circuit reversed allodynia, whereas the enhancement of its activity provoked hyperalgesia in control mice. In addition, we found that the expression and function of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) were increased in VPLGlu neurons under conditions of chronic pain. Using in vivo calcium imaging, we demonstrated that downregulation of HCN2 channels in the VPLGlu neurons abrogated the rise in S1HLGlu neuronal activity while alleviating allodynia in mice with chronic pain. With these data, we propose that dysfunction in HCN2 channels in the VPLGlu→S1HLGlu thalamocortical circuit and their upregulation occupy essential roles in the development of chronic pain.

Oxidative Stress and Pyroptosis in Doxorubicin-Induced Heart Failure and Atrial Fibrillation.

Patients undergoing doxorubicin (Dox) chemotherapy often develop new-onset atrial fibrillation and heart failure. Recent studies indicate that the TLR4/MyD88/NLRP3 pyroptosis signaling pathway plays a key role in the occurrence and development of cancer, heart failure, and atherosclerosis. However, few studies investigated the role of oxidative stress and pyroptosis in doxorubicin-induced heart failure and new-onset atrial fibrillation. In this study, we recruited 84 healthy subjects, 112 patients undergoing Dox chemotherapy showing heart failure (HF), and 62 patients undergoing Dox treatment who manifested atrial fibrillation (AF). The mRNA and protein levels of TLR4 expression, several downstream pyroptosis-associated proteins (cleaved caspase-1, NLRP3, GSDMD-N, and HMGB-1), serum inflammatory factors, and oxidative stress were detected at the beginning of chemotherapy and after 3 months of Dox chemotherapy. Oxidative stress and downstream pyroptosis-associated proteins tended to increase in the Dox-baseline group to the Dox-HF group. However, virtually no change in the expression of either oxidative stress or pyroptosis-associated proteins was detected in patients after three months of Dox chemotherapy compared with those at baseline. This study suggests that the prolonged oxidative stress and high levels of pyroptosis-associated proteins contribute to cardiac systolic dysfunction, suggesting TLR4 as a novel biomarker and a potential treatment target for doxorubicin-induced heart failure.

A neural circuit for the suppression of feeding under persistent pain.

In humans, persistent pain often leads to decreased appetite. However, the neural circuits underlying this behaviour remain unclear. Here, we show that a circuit arising from glutamatergic neurons in the anterior cingulate cortex (GluACC) projects to glutamatergic neurons in the lateral hypothalamic area (GluLHA) to blunt food intake in a mouse model of persistent pain. In turn, these GluLHA neurons project to pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus (POMCArc), a well-known neuronal population involved in decreasing food intake. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that the GluACC → GluLHA → Arc circuit is activated in mouse models of persistent pain and is accompanied by decreased feeding behaviour in both males and females. Inhibition of this circuit using chemogenetics can alleviate the feeding suppression symptoms. Our study indicates that the GluACC → GluLHA → Arc circuit is involved in driving the suppression of feeding under persistent pain through POMC neuronal activity. This previously unrecognized pathway could be explored as a potential target for pain-associated diseases.

Trends in Postoperative Intensity-Modulated Radiation Therapy Use and Its Association With Survival Among Patients With Incompletely Resected Non-Small Cell Lung Cancer.

Importance: National guidelines allow consideration of postoperative radiation therapy (PORT) among patients with incompletely resected non-small cell lung cancer (NSCLC). However, there is a paucity of prospective data because recently completed trials excluded patients with positive surgical margins. In addition, unlike for locally advanced NSCLC, the role of intensity-modulated radiation therapy (IMRT) for PORT remains unclear. Objective: To evaluate trends of IMRT use for PORT in the US and the association of IMRT with survival outcomes among patients with incompletely resected NSCLC. Design, Setting, and Participants: This retrospective cohort study used data from the National Cancer Database for patients diagnosed between January 2004 and December 2019 with incompletely resected NSCLC who underwent upfront surgery with positive surgical margins followed by PORT. Exposures: IMRT vs 3D conformal radiation therapy (3DCRT) for PORT. Main Outcomes and Measures: The main outcome was overall survival. Multivariable Cox proportional hazards regression assessed the association of IMRT vs 3DCRT with overall survival. Multivariable logistic regression identified variables associated with IMRT. Propensity score matching (1:1) was performed based on variables of interest. Results: A total of 4483 patients (2439 men [54.4%]; median age, 67 years [IQR, 60-73 years]) were included in the analysis. Of those, 2116 (47.2%) underwent 3DCRT and 2367 (52.8%) underwent IMRT. Median follow-up was 48.5 months (IQR, 31.1-77.2 months). The proportion of patients who underwent IMRT increased from 14.3% (13 of 91 patients) in 2004 to 70.7% (33 of 471 patients) in 2019 (P < .001). IMRT was associated with improved overall survival compared with 3DCRT (adjusted hazard ratio, 0.84; 95% CI, 0.78-0.91; P < .001). Similar findings were observed for 1463 propensity score-matched pairs; IMRT was associated with improved 5-year overall survival compared with 3DCRT (37.3% vs 32.2%; hazard ratio, 0.88; 95% CI, 0.80-0.96; P = .003). IMRT use was associated with receipt of treatment at an academic facility (adjusted odds ratio [aOR], 1.15; 95% CI, 1.00-1.33; P = .049), having T4 stage tumors (aOR, 1.50; 95% CI, 1.13-1.99; P = .005) or N2 or N3 stage tumors (aOR, 1.25; 95% CI, 1.04-1.51; P = .02), and receipt of pneumonectomy (aOR, 1.35; 95% CI, 1.02-1.80; P = .04). Conclusion and Relevance: This cohort study found that use of IMRT for PORT among patients with incompletely resected NSCLC increased in the US from 2004 to 2019 and was associated with improved survival compared with 3DCRT. Further studies are warranted to investigate the role of different radiation therapy techniques for PORT.

Efficacy and Safety of Ultrafiltration in Patients with Heart Failure: A Single-Center Experience.

INTRODUCTION: There is a paucity of literature on the efficacy and safety of ultrafiltration in Chinese patients with heart failure (HF). Therefore, we aimed to compare the efficacy and safety of ultrafiltration with diuretics and provide information and evidence as to the best approach for patients with HF. METHODS: In this single-center, non-randomized interventional study patients with HF either received diuretics or ultrafiltration. The efficacy outcomes included changes in the weight, dyspnea score, and 6-min walk distance from baseline to 48 h after treatment. Safety outcomes were evaluated in both the groups with respect to changes in systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium ion concentration, and blood sodium ion concentration. RESULTS: A total of 149 patients with HF (diuretics, 73; ultrafiltration, 76) were included. At 48 h, patients in the ultrafiltration group showed significantly greater weight loss and better improvement in dyspnea score and 6-min walk distance compared to patients in the control group (P < 0.05). However, the two groups showed no statistically significant difference in terms of safety outcomes such as systolic blood pressure, heart rate, serum creatinine, blood urea nitrogen, blood potassium ion concentration, and blood sodium ion concentration, suggesting similar safety profiles of both the groups. CONCLUSION: Ultrafiltration was associated with greater weight loss and better dyspnea score and 6-min walk distance with similar safety profiles as compared with diuretics. Ultrafiltration can be considered as an optimal option for Chinese patients with HF.

Exosomes Derived from M2 Macrophages Exert a Therapeutic Effect via Inhibition of the PI3K/AKT/mTOR Pathway in Rats with Knee Osteoarthritic.

Macrophages are commonly classified as M1 macrophages or M2 macrophages. M2 macrophages are obtained by stimulation of IL-4 with anti-inflammatory and tissue repair effects. Exosomes are 30-150 nm lipid bilayer membrane vesicles derived from most living cells and have a variety of biological functions. Previous studies have shown that macrophage exosomes can influence the course of some autoimmune diseases, but their effect on knee osteoarthritis (KOA) has not been reported. Here, we analyze the roles of exosomes derived from M2 macrophage phenotypes in KOA rats. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), Western blotting, and DLS. The results showed that M2 macrophage exosomes significantly attenuated the inflammatory response and pathological damage of articular cartilage in KOA rats. In addition, a key protein associated with KOA including Aggrecan, Col-10, SOX6, and Runx2 was significantly increased, while MMP-13 was significantly suppressed following treatment with M2 macrophage exosomes. The present study indicated that M2 macrophage exosomes exerted protective effects on KOA rats mainly mediated by the PI3K/AKT/mTOR signal pathway. These findings provide a novel approach for the treatment of KOA.

Comparison of a tube core and Magill forceps for nasotracheal intubation: a randomised controlled trial.

BACKGROUND: Magill forceps are frequently used to complete nasotracheal intubation (NTI). We aimed to identify a tube core that could conveniently facilitate the NTI process without using Magill forceps. METHODS: Sixty patients scheduled for oral and maxillofacial surgeries were enrolled in our study and divided into two groups (30 per group) with no differences with regard to demographic data. In the Magill forceps group (Group M), a wire-reinforced endotracheal catheter was inserted into the trachea using Magill forceps. However, in the tube core group (Group T), a tube core bent to the physiological curve of the nasal cavity and lubricated with aseptic paraffin oil was inserted into the endotracheal catheter and was then withdrawn after the endotracheal catheter was advanced through the glottis under direct vision. RESULTS: All NTIs were completed successfully, and Magill forceps were not used on any patient in Group T. There was a significant difference in total NTI time between the two groups (Group M, 59.7 (5.1) s vs Group T, 52.4 (3.1) s). Mild epistaxis was observed in 6 patients in Group M and 5 patients in Group T (6/30 vs 5/30, respectively). No damage to oral tissue or teeth was observed in either group. CONCLUSIONS: We conclude that using a tube core, consisting of a disposable sterilised stylet, is a convenient choice for NTI. TRIAL REGISTRATION: Patient enrolment was conducted after registration in the Chinese Clinical Trial Registry ( www.Chictr.org.cn , ChiCTR190002 7387). This trial was prospectively registered on 11 November 2019.

Effect of levosimendan combined with recombinant human brain natriuretic peptide on diuretic resistance.

Levosimendan is a calcium sensitizer used for managing heart failure (HF) because of its inotropic and vasodilatory effects. As many patients do not respond to levosimendan as a monotherapy, it may be necessary to combine it with other diuretic agents such as recombinant human brain natriuretic peptide (rhBNc P). The aim of this study was to investigate efficacy of levosimendan when combined with rhBNP in patients with diuretic resistance and low ejection fraction (EF) rate.The study included HF patients with diuretic resistance and low EF. Before grouping, patients with a 24-hour urine volume of <0.5 mL/kg/h were administered with furosemide injection. Treatment group was administered levosimendan injection based on the original diuretic and rhBNP.One hundred twenty-eight patients were included, with 64 patients each in the control and treatment arms. 24-hour urine volume of the treatment group was significantly higher than that of the control group. Moreover, dyspnea score of the treatment group significantly improved compared with control group. In the treatment group, 12.5% of patients had no significant changes in the urine volume, weight, and dyspnea score before and after the treatment, indicating poor curative effect of the treatment, whereas in the control group, 23.4% of patients had poor curative effect (P < .05). No significant change was observed in the systolic blood pressure, heart rate, and serum creatinine level before and after treatment in both groups.Levosimendan in combination with rhBNP can effectively relieve diuretic resistance, reduce body weight, improve dyspnea, and ensure safety in the treatment process.