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.

The Effect of Unintended Facet Arthrodesis on the Treatment Outcome of Dynamic Neutralization System for Lumbar Degenerative Diseases.

Purpose: This study aimed to examine the influence of unintended facet arthrodesis on the therapeutic effectiveness of the dynamic neutralization system (Dynesys). Methods: This retrospective study enrolled consecutive patients who underwent posterior decompression and dynamic stabilization for lumbar spondylosis or spinal stenosis. Follow-up assessments included lumbar radiography, lumbar vertebral computerized tomography (CT), visual analog scale (VAS), and Oswestry disability index (ODI). Patients were classified into the facet fusion and non-fusion groups. The differences in the VAS scores for back pain and leg pain, ODI, intervertebral range of motion (ROM) at the surgical segments, and upper adjacent segments were assessed before and after treatment. Results: A total of 49 patients (29 males and 20 females) aged 31-65 years were enrolled and followed-up for over 40 months. Among the patients, 16 (32.7%) experienced unintended facet arthrodesis and were assigned to the fusion group, whereas the remaining patients were assigned to the non-fusion group. There was a significant increase in the incidence of facet arthrodesis in the surgical segments over time post-surgery (χ2 = 6.2, p < 0.05). The ROM of the surgical and upper adjacent segments, VAS scores for back pain and leg pain, and ODI were all significantly different before and after the operation (p < 0.05), but not between the fusion and non-fusion groups (p > 0.05). Conclusion: Although unintended facet arthrodesis is common after Dynesys procedure, the presence of facet arthrodesis does not significantly affect the efficacy of Dynesys in treating lumbar degenerative diseases.

Laurolitsine ameliorates type 2 diabetes by regulating the hepatic LKB1-AMPK pathway and gut microbiota.

BACKGROUND: Type 2 diabetes mellitus (DM) is a highly prevalent chronic metabolic disease. Effective antidiabetic drugs are needed to improve and expand the available treatments. Using the ob/ob diabetic mouse model, we previously demonstrated that the alkaloid-rich extract from Litsea glutinosa bark (CG) has potent antidiabetic effects and that laurolitsine (LL) is the richest alkaloid in CG. PURPOSE: We conducted a systematic investigation of the antidiabetic effects and potential mechanisms of LL in vitro and in vivo. METHODS: The antidiabetic effects of LL and its mechanisms of action were explored in HL-7702 hepatocytes in vitro and in db/db mice in vivo by a series of experiments, including cellular toxicity analysis, glucose consumption analysis, serum/liver biochemical analysis, pathological examinations, Western blots, RNA-seq analysis, and gut microbiota analysis. RESULTS: LL stimulated glucose consumption and activated AMP-activated protein kinase (AMPK) without inducing lactic acid production or cytotoxicity in vitro. LL had potent antidiabetic effects with hypoglycemic activity in vivo. It improved insulin resistance, glucose tolerance and lipid metabolism; protected liver, renal and pancreatic functions; and promoted weight loss in db/db mice. Transcriptomic analysis suggested that the antidiabetic effects of LL involved the regulation of mitochondrial oxidative phosphorylation. We further demonstrated that LL effectively activated the hepatic liver kinase B1 (LKB1)/AMPK pathway by regulating the ADP/ATP ratio. Simultaneously, LL significantly modulated the gut microbial community, specifically decreasing the abundances of Mucispirillum schaedleri and Anaerotruncus_sp_G3_2012, which might also contribute to its antidiabetic effects. CONCLUSION: These results suggest that LL is a promising antidiabetic drug candidate that may improve glucolipid metabolism via modulation of the hepatic LKB1/AMPK pathway and the gut microbiota.

Characterization of a novel aminopeptidase P from Trichinella spiralis and its participation in the intrusion of intestinal epithelial cells.

Aminopeptidases P are metalloproteases belonging to the M24 peptidase family. It specifically hydrolyzes the N-terminus of polypeptides free of acidic amino acids, and plays an important role in the nutrition, metabolism and growth of parasites. The aim of this study was to characterize a novel Trichinella spiralis aminopeptidase P (TsAPP) and to investigate its functions in the invasion of T. spiralis. TsAPP contained two domains of creatinase (a creatinase N and creatinase N2) and a domain of peptidase M24C and APP. The complete TsAPP sequence was cloned and expressed in Escherichia coli BL21 cells. The recombinantly produced TsAPP was used to raise polyclonal antibodies that were subsequently used to detect the expression of the protein in the different life stages of T. spiralis. TsAPP was expressed in various T. spiralis stages. TsAPP was primarily localized in the cuticle, stichosome and intrauterine embryos of this nematode. rTsAPP has an enzymatic activity of a natural aminopeptidase P to hydrolyze the substrate H-Ala-Pro-OH. rTsAPP promoted the larval intrusion of intestinal epithelium cells (IECs). The results showed that TsAPP is involved in the T. spiralis intrusion of IECs and it might be a potential candidate vaccine target against Trichinella infection.

Nootkatone, a Sesquiterpene Ketone From Alpiniae oxyphyllae Fructus, Ameliorates Metabolic-Associated Fatty Liver by Regulating AMPK and MAPK Signaling.

Metabolic-associated fatty liver disease (MAFLD) is becoming more common due to lifestyle changes. A long-term high-fat and high-glucose diet induces glycolipid metabolism disorders in the liver, which results in the development of MAFLD. To date, there is no specific clinically useful therapeutics for this disease. Natural products or synthetic compounds were screened and investigated to find effective agents for treating MAFLD. In this study, nootkatone (Nok), a natural sesquiterpene ketone isolated from Alpiniae oxyphyllae fructus, was explored for its potential to treat MAFLD, and underlying mechanisms were studied. Our results show that Nok dramatically ameliorated the disordered lipid and glucose metabolism in MAFLD mice, decreased fat accumulation in hepatic tissue, and improved liver injury. Inflammation, metabolic disorder, and oxidative stress were ameliorated in liver tissue based on RNA-seq transcriptome comparison between a Nok-treated group and an MAFLD model group. Furthermore, Nok significantly activated AMPK activity and inhibited MAPK activity, especially the p38 and JNK signaling pathways, in vivo based on western blot analysis. The pharmaceutical effects and potential signaling pathways impacted by Nok were also investigated in L02 cells. Nok significantly promoted the consumption of glucose and decreased the deposition of triglycerides in vitro. The p-AMPKα level was notably upregulated by Nok, indicating dramatic AMPK activation. In addition, Nok decreased the levels of p-ERK1/2, p-p38, and p-JNK. Nok also inhibited the activation of MAPK signaling and, thus, alleviated MAFLD development. Our results suggest that Nok may be useful in treating MAFLD. Nok may ameliorate MAFLD by regulating glycolipid metabolism disorders by activating AMPK and inhibiting MAPK activity. Collectively, this study suggests that Nok is an effective compound for the treatment of MAFLD.

Taurine Ameliorates Streptozotocin-Induced Diabetes by Modulating Hepatic Glucose Metabolism and Oxidative Stress in Mice.

Taurine is a sulfated amino acid derivative that plays an important role in maintaining the cell function of the living body. Although taurine has been shown to ameliorate diabetes, its mechanism of action has not yet been fully elucidated. The present study investigated the effects of taurine on diabetes focusing on glucose metabolism and oxidative stress. Type 1 diabetes was induced by the administration of streptozotocin (STZ) to male C57BL/6J mice. Taurine was dissolved in drinking water at 3% (w/v) and allowed to be freely ingested by diabetic mice. The weight and blood glucose levels were measured weekly. After nine weeks, mice were sacrificed and their serum, liver, and kidney were removed and used for biochemical and histological analyses. A microarray analysis was also performed in normal mice. Taurine alleviated STZ-induced hyperglycemia and hyperketonemia, accompanied by the suppression of the decrease in hepatic glycogen and upregulation of the mRNA expression of hepatic glucose transporter GLUT-2. Furthermore, STZ-induced elevation of oxidative stress in the liver and kidney was suppressed by taurine treatment. These results showed that taurine ameliorated diabetes and diabetic complications by improving hepatic glucose metabolism and reducing oxidative stress.

Untargeted and Targeted Metabolomics Reveal the Underlying Mechanism of Aspirin Eugenol Ester Ameliorating Rat Hyperlipidemia via Inhibiting FXR to Induce CYP7A1.

Hyperlipidemia is an important lipid disorder and a risk factor for health. Aspirin eugenol ester (AEE) is a novel synthetic compound which is made up of two chemical structural units from aspirin and eugenol. Therapeutic effect of AEE on hyperlipidemia has been confirmed in animal model. But the action mechanism of AEE on hyperlipidemia is still poorly understood. In this study, we investigated the effects of AEE on liver and feces metabolic profile through UPLC-Q-TOF/MS-based untargeted metabolomics in hyperlipidemia hamster induced with high fat diet (HFD), and the effects of AEE on the expression of genes and proteins related to cholesterol and bile acid (BA) in HFD-induced hyperlipidemia SD rat. The concentrations of 26 bile acids (BAs) in the liver from hyperlipidemia SD rat were also quantified with the application of BA targeted metabolomics. The results of untargeted metabolomics showed that the underlying mechanism of AEE on hyperlipidemia was mainly associated with amino acid metabolism, glutathione metabolism, energy metabolism, BA metabolism, and glycerophospholipid metabolism. AEE induced the expression of the BA-synthetic enzymes cholesterol 7α-hydroxylase (CYP7A1) by the inhibition of BA nuclear receptor farnesoid X receptor (FXR) in liver, which resulted in accelerating the conversion of cholesterol into bile acids and excrete in feces. The results of BA targeted metabolomics showed that AEE elevated the glycine-conjugated BA level and decreased the tauro-conjugated BA level. In conclusion, this study found that AEE decreased FXR and increased CYP7A1 in the liver, which might be the possible molecular mechanisms and targets of AEE for anti-hyperlipidemia therapies.

Mangiferin Ameliorates HFD-Induced NAFLD through Regulation of the AMPK and NLRP3 Inflammasome Signal Pathways.

Nonalcoholic fatty liver disease (NAFLD) is closely related to glycolipid metabolism and liver inflammation. And there is no effective drug approved for its clinical therapy. In this study, we focused on mangiferin (Man) and explored its effects and mechanisms on NAFLD treatment based on the regulation of glycolipid metabolism and anti-inflammatory in vivo and in vitro. The results exhibited that Man can significantly attenuate liver injury, insulin resistance, and glucose tolerance in high-fat diet- (HFD-) induced NAFLD mice and significantly reduce fat accumulation and inflammation in hepatic tissue of NAFLD mice. The transcriptome level RNA-seq analysis showed that the significantly different expression genes between the Man treatment group and the HFD-induced NAFLD model group were mainly related to regulation of energy, metabolism, and inflammation in liver tissue. Furthermore, western blots, real-time PCR, and immunohistochemistry experiments confirmed that Man significantly activated the AMPK signal pathway and inhibited NLRP3 inflammasome activation and pyroptosis in NAFLD mice. In in vitro cell experiments, we further confirmed that Man can promote glucose consumption and reduce intracellular triglyceride (TG) accumulation induced by free fatty acids in HepG2 cells and further that it can be blocked by AMPK-specific inhibitors. Western blot results showed that Man upregulated p-AMPKα levels and exhibited a significant AMPK activation effect, which was blocked by compound C. At the same time, Man downregulated the expression of NLRP3 inflammasome-related proteins and inhibited the activation of NLRP3 inflammasome, alleviating cell pyroptosis and inflammation effects. These results indicate that Man anti-NAFLD activity is mediated through its regulation of glucolipid metabolism by AMPK activation and its anti-inflammatory effects by NLRP3 inflammasome inhibition. Our study indicates that Man is a promising prodrug for the therapy of NAFLD patients.

Symmetry in Paraspinal Muscles as a Predictor of the Development of Pregnancy-Related Low Back and Pelvic Pain: A Prospective Study.

OBJECTIVE: To determine the asymmetry in the paraspinal muscle before pregnancy and evaluate its association with pregnancy-associated lumbopelvic pain (LPP). METHODS: This was a prospective case-control study conducted from January 2017 and December 2018. A total of 171 subjects (mean age ± SD, 27.4 ± 5.8 years) were finally divided into the LBP group, PGP group, and no LPP group. Each subject was asked to follow a standardized clinical imaging protocol before the pregnancy. The area of muscles (multifidus, erector spinae, and psoas muscles) on the axial slice at mid-disc of L4 -L5 and L5 -S1 were segmented and then the cross-sectional area (CSA) of a particular muscle was measured by outlining the innermost fascial border surrounding each muscle. The mean value of F-CSA's ratio to T-CSA (F/T CSA) was used to determine whether the bilateral paraspinal muscle was asymmetrical. Total muscle CSA (T-CSA) represents the sum of CSA of interested three muscles. The signal intensity can distinguish fat and muscle tissue in a different range. Based on this, functional CSA (F-CSA), represented by fat-free area, was evaluated quantitively by excluding the signal of the deposits of intramuscular fat. Total muscle CSA (T-CSA), functional CSA (F-CSA), and the ratio of F-CSA to T-CSA (F/T CSA) were measured unilaterally and compared between groups. Logistic regression was performed to determine the risk factors for pregnancy-associated LPP. The Pearson correlation coefficient was performed to test the relationship between asymmetry in F/T-CSA and pain rating. RESULTS: A total of 124 subjects (72.5%) (28.5 ± 5.2 years) had LPP during pregnancy. Forty-eight (38.7%) individuals had low back pain (LBP) and 76 (61.3%) had pelvic girdle pain (PGP). Seventy-six women (44.4%) were determined to have asymmetry in paraspinal muscle according to the definition in this methods section. The duration of follow-up was 24 months postpartum. A total of 39 (31.5%) women unrecovered from LPP. F/T-CSA was significantly decreased for LBP in the PGP group than in the and control group (0.03 ± 0.02 vs 0.05 ± 0.03 vs 0.12 ± 0.05, P < 0.001). Meanwhile, significant differences were detected in both groups (all P < 0.001). In patients with LBP, the level of paraspinal asymmetry, represented by the difference in F/T-CSA, was positively correlated with pain scores (r = 0.52, P < 0.01). However, no statistically significant correlation between pain scores and paraspinal asymmetry was found in PGP (r = 0.42, P > 0.05). Asymmetry in the paraspinal muscle (adjusted OR = 1.5), LBP (adjusted OR = 1.6), LPP in a previous pregnancy (adjusted OR = 1.4), sick leave ≥90 days (adjusted OR = 1.2), and heavy labor (adjusted OR = 1.2) were risk factors for the unrecovered LPP during pregnancy. CONCLUSIONS: Asymmetrical muscular compositions could lead to abnormal biomechanics for the segmental motions. Lateral-directed physical training and stretching may help decrease the occurrence and severity of this condition.

[Comparison of treatment outcomes in patients with maxillary dentoalveolar protrusion by applying different anchorage methods: a three-dimensional model study].

OBJECTIVE: This study aims to compare the treatment outcomes in patients with maxillary dentoalveolar protrusion by applying different anchorage methods via three-dimensional model measurement. METHODS: A total of 46 patients with maxillary dentoalveolar protrusion treated with bilateral maxillary first premolar extractions and high anchorage were selected. The subjects were randomly divided into three groups according to the type of anchorage applied, which included implant, extraoral, and Nance arch anchorages. The maxillary dental models were made before treatment and after space closure of maxilla. The movements of the maxillary central incisors and first molars were measured via a three-dimensional model measurement, and the amounts of movement were compared among the three groups. RESULTS: The sagittal lingual movements of the maxillary central incisors were (-6.661 ± 1.328), (-5.939 ± 1.806), and (-5.788 ± 2.009) mm for the implant, extraoral, and Nance arch anchorage groups, respectively, with no significant difference among the three groups (P = 0.121). The corresponding vertical movements of the maxillary central incisors were (0.129 ± 1.815) mm intrusion, and (-2.162 ± 2.026), (-2.623 ± 1.776) mm extrusion. Significant difference was found between the implant anchorage group and the other groups (P < 0.05). The corresponding sagittal mesial movements of the maxillary first molars were (0.608 ± 1.045), (1.445 ± 1.462), and (1.503 ± 0.945) mm. The corresponding vertical movements of the maxillary first molars were (0.720 ± 0.805) mm intrusion, (0.076 ± 0.986) mm intrusion, and (-0.072 ± 0.690) mm extrusion. Significant difference was found between the implant anchorage group and the other two groups (P < 0.05). In the transverse direction, the first molars all moved lingually with no significant difference among the three groups (P > 0.05). CONCLUSION: Implant anchorage may be superior in the vertical control of the maxillary incisors and in the sagittal, as well as in the vertical control of the maxillary molars, compared with the traditional anchorages during the treatment of patients with maxillary dentoalveolar protrusion.

[The pedicled anterolateral thigh flap for penile reconstruction].

OBJECTIVE: To introduce the application of pedicled anterolateral thigh (ALT) flap for total penile reconstruction and to investigate its feasibility and effect. METHODS: From May 2011 to May 2015, 12 male patients presented with absence of the penis or congenital malformation received phalloplasty with the pedicled ALT flap. Of them, the median age was 35 years old (range, 20-57 years). The size of the flaps ranged from 11 cm x 11 cm to 12 cm x 15 cm. 8 patients underwent urethra reconstruction with tube-in-tube flaps and other 4 patients with scrotal septal flaps. In this series, we performed one-stage urethral anastomosis in 4 cases and second-stage urethral anastomosis 6 months after the phalloplasty in 8 cases. RESULTS: An acceptable reconstructed phallus was achieved in 10 patients. These flaps were primarily healed with satisfactory functional and cosmetic results. The reconstructed penis was completely necrosis because of the flap failure in one case. The distal half of the phallus was lost due to infection in one case. Both of them were treated with pedicled ALT flap from the other side. Reliable results were achieved. At a median follow-up of 1.5 year (range 1 to 4 years), 9 patients (90%) were fully satisfied with phallic cosmesis and size, and 4 patients who was married had successful sexual intercourse. 8 patients had normal urinate function. Fistula was developed in 2 patients (20%) which was treated with delayed repair at 6-12 months with local scrotal flaps. CONCLUSIONS: The pedicled ALT flap can be simply used to reconstruct an entire penis as well as a urethra. It has several advantages including a less conspicuous donor site, greater bulk, better color match and no necessary for microsurgery.

[Reconstruction of facial soft tissue defects with pedicled expanded flaps].

OBJECTIVE: To investigate the application of pedicled expanded flaps for the reconstruction of facial soft tissue defects. METHODS: The expanded skin flaps, pedicled with orbicularis oculi muscle, submental artery, the branch of facial artery, superficial temporal artery, interior upper arm artery, had similar texture and color as facial soft tissue. The pedicled expanded flaps have repaired the facial soft tissue defects. RESULTS: Between Jan. 2003 to Dec. 2013, 157 cases with facial soft tissue defects were reconstructed by pedicled expanded flaps. Epidermal necrosis happened at the distal end of 8 expanded flaps, pedicled with interior upper arm artery(4 cases), orbicularis oculi muscle(3 cases) and submental artery(1 case), which healed spontaneously after dressing. All the other flaps survived completely with similar color and inconspicuous scar. 112 cases were followed up for 8 months to 8 years. Satisfactory results were achieved in 75 cases. 37 cases with hypertrophic scar at incisions need secondary operation. CONCLUSIONS: Island pedicled expanded flap with similar texture and color as facial soft tissue is suitable for facial soft tissue defects. The facial extra-incision and large dog-ear deformity could be avoided.

[Clinical observation of erhuang powder's promoting the wound healing of cervical columnar epithelium ectopy after physiotherapy].

OBJECTIVE: To observe the clinical effects of Erhuang Powder (EHP) in promoting the wound healing of cervical columnar epithelium ectopy after physiotherapy. METHODS: Sixty-four patients with moderate and severe cervical columnar epithelium ectopy accompanied with contact bleeding were assigned to the treatment group (34 cases) and the control group (30 cases) according to table of random digit. Physiotherapy of the cervix was given to all patients. EHP was externally applied to the affected site of patients in the treatment group once every 3 days. Five times consisted as one therapeutic course, totally for 2 courses. The therapeutic effects, the wound healing time, the vaginal fluid quantity, the vaginal fluid discharge time, the wound infection, and adverse reaction were observed in the two groups. RESULTS: The healing rate of the treatment group was 85.29% (29/34), higher than that of the control group (50%, 15/30) after 8 weeks of treatment, showing statistical difference (P < 0.1). The average wound healing time of the treatment group (3.2 - 0.8 weeks) was shorter than that of the control group (5.3 +/- 0.9 weeks), showing statistical difference (P < 0.5). The vaginal fluid quantity and the vaginal fluid discharge time in the treatment group were superior to those in the control group, showing statistical difference (P < 0.5, P < 0.1). Increased vaginal secretion accompanied with foreign odor or infection occurred in 2 patients of the control group. No adverse reaction or infection occurred in the treatment group. CONCLUSIONS: Local application of EHP could promote the wound healing of cervical columnar epithelium ectopy after physiotherapy. It could improve its healing rate. Therefore, it was one ideal and reliable method, and worthy of clinical spreading.