[Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning].

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Double Superconducting Dome and Triple Enhancement of T_{c} in the Kagome Superconductor CsV_{3}Sb_{5} under High Pressure.

CsV_{3}Sb_{5} is a newly discovered Z_{2} topological kagome metal showing the coexistence of a charge-density-wave (CDW)-like order at T^{*}=94 K and superconductivity (SC) at T_{c}=2.5 K at ambient pressure. Here, we study the interplay between CDW and SC in CsV_{3}Sb_{5} via measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6.6 GPa. We find that the CDW transition decreases with pressure and experience a subtle modification at P_{c1}≈0.6-0.9 GPa before it vanishes completely at P_{c2}≈2 GPa. Correspondingly, T_{c}(P) displays an unusual M-shaped double dome with two maxima around P_{c1} and P_{c2}, respectively, leading to a tripled enhancement of T_{c} to about 8 K at 2 GPa. The obtained temperature-pressure phase diagram resembles those of unconventional superconductors, illustrating an intimated competition between CDW-like order and SC. The competition is found to be particularly strong for the intermediate pressure range P_{c1}≤P≤P_{c2} as evidenced by the broad superconducting transition and reduced superconducting volume fraction. The modification of CDW order around P_{c1} has been discussed based on the band structure calculations. This work not only demonstrates the potential to raise T_{c} of the V-based kagome superconductors, but also offers more insights into the rich physics related to the electron correlations in this novel family of topological kagome metals.

[Clinical and immunological characteristics of patients with anti-synthetase syndrome complicated with cardiac involvement].

OBJECTIVE: To investigate the clinical and immunological features of cardiac involvement in patients with anti-synthetase syndrome (ASS). METHODS: In the study, 96 patients diagnosed with ASS hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital from April 2003 to November 2020 were included. The patients were divided into two groups according to whether they were accompanied with cardiac involvement. Demographic features, clinical characteristics (Gottron's sign/papules, muscle damage, etc.), comorbidities, laboratory indices (creatine kinase, inflammatory indicators, immunoglobulin, complement, lymphocyte subset, autoantibodies, etc.) were collected and the differences between the two groups were analyzed statistically. RESULTS: The prevalence of cardiac involvement in the patients with ASS was 25.0% (24/96). The ASS patients complicated with cardiac involvement presented with elevated cardiac troponin I (cTnI, 75.0%, 18/24), pericardial effusion (33.3%, 8/24), reduction of left ventricular function (33.3%, 8/24) and valves regurgitation (33.3%, 8/24). The age of onset of the patients with cardiac involvement was older than that of the patients without cardiac involvement [(54.58±10.58) years vs. (48.47±13.22) years, P=0.043). Arthritis was observed less frequently in the patients with cardiac involvement than those without cardiac involvement (37.5% vs. 61.1%, P=0.044). In addition, rapidly progressive interstitial lung disease (54.2% vs. 30.6%, P=0.037) was observed more frequently in the patients with cardiac involvement than those without cardiac involvement. As compared with the ASS patients without cardiac involvement, C-reactive protein (CRP) [(13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001], and lactate dehydrogenase (LDH) [408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007] were significantly higher in the patients with cardiac involvement. Anti-Ro-52 antibody was detected more commonly in the ASS patients with cardiac involvement compared with the patients without cardiac involvement (91.7% vs. 69.4%, P=0.029). No significant differences were found in the comorbidities, alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), erythrocyte sedimentation rate (ESR), ferritin (Fer), immunoglobulin G (IgG), complement 3 (C3), complement 4 (C4), lymphocyte subset between the two groups. CONCLUSION: Cardiac involvement is common in ASS, mainly manifested as myocardial damage. It is necessary to be aware of cardiac complications in patients with elevated CRP, elevated LDH and positive anti-Ro-52 antibody.

Criterion for optimizing high-power acousto-optically Q-switched self-Raman yellow lasers with repetition rates up to 500 kHz.

The criterion for optimizing the high-power acousto-optically ${Q}$Q-switched self-Raman yellow laser is originally explored for the repetition rate within 100-500 kHz. The minimum allowed value for the gate-open time is experimentally verified to be determined by the pulse buildup time. By using the minimum allowed gate-open time, the highest conversion efficiency can be achieved to raise the output power by approximately 20% in comparison with the conventional results. At a repetition rate of 200 kHz, the maximum output power at 588 nm can be up to 8.8 W at an incident pump power of 26 W. Furthermore, a practical formula is developed to accurately calculate the threshold pump power as a function of the gate-open time for a given repetition rate.

Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke.

BACKGROUND AND PURPOSE: Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. METHODS: After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. RESULTS: The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. CONCLUSIONS: Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.

WHITE STRIPE LEAF8, encoding a deoxyribonucleoside kinase, is involved in chloroplast development in rice.

KEY MESSAGE: WSL8 encoding a deoxyribonucleoside kinase (dNK) that catalyzes the first step in the salvage pathway of nucleotide synthesis plays an important role in early chloroplast development in rice. The chloroplast is an organelle that converts light energy into chemical energy; therefore, the normal differentiation and development of chloroplast are pivotal for plant survival. Deoxyribonucleoside kinases (dNKs) play an important role in the salvage pathway of nucleotides. However, the relationship between dNKs and chloroplast development remains elusive. Here, we identified a white stripe leaf 8 (wsl8) mutant that exhibited a white stripe leaf phenotype at seedling stage (before the four-leaf stage). The mutant showed a significantly lower chlorophyll content and defective chloroplast morphology, whereas higher reactive oxygen species than the wild type. As the leaf developed, the chlorotic mutant plants gradually turned green, accompanied by the restoration in chlorophyll accumulation and chloroplast ultrastructure. Map-based cloning revealed that WSL8 encodes a dNK on chromosome 5. Compared with the wild type, a C-to-G single base substitution occurred in the wsl8 mutant, which caused a missense mutation (Leu 349 Val) and significantly reduced dNK enzyme activity. A subcellular localization experiment showed the WSL8 protein was targeted in the chloroplast and its transcripts were expressed in various tissues, with more abundance in young leaves and nodes. Ribosome and RNA-sequencing analysis indicated that some components and genes related to ribosome biosynthesis were down-regulated in the mutant. An exogenous feeding experiment suggested that the WSL8 performed the enzymic activity of thymidine kinase, especially functioning in the salvage synthesis of thymidine monophosphate. Our results highlight that the salvage pathway mediated by the dNK is essential for early chloroplast development in rice.

Recombination of the Phase-Variable spnIII Locus Is Independent of All Known Pneumococcal Site-Specific Recombinases.

Streptococcus pneumoniae is one of the world's leading bacterial pathogens, causing pneumonia, septicemia, and meningitis. In recent years, it has been shown that genetic rearrangements in a type I restriction-modification system (SpnIII) can impact colony morphology and gene expression. By generating a large panel of mutant strains, we have confirmed a previously reported result that the CreX (also known as IvrR and PsrA) recombinase found within the locus is not essential for hsdS inversions. In addition, mutants of homologous recombination pathways also undergo hsdS inversions. In this work, we have shown that these genetic rearrangements, which result in different patterns of genome methylation, occur across a wide variety of serotypes and sequence types, including two strains (a 19F and a 6B strain) naturally lacking CreX. Our gene expression analysis, by transcriptome sequencing (RNAseq), confirms that the level of creX expression is impacted by these genomic rearrangements. In addition, we have shown that the frequency of hsdS recombination is temperature dependent. Most importantly, we have demonstrated that the other known pneumococcal site-specific recombinases XerD, XerS, and SPD_0921 are not involved in spnIII recombination, suggesting that a currently unknown mechanism is responsible for the recombination of these phase-variable type I systems.IMPORTANCEStreptococcus pneumoniae is a leading cause of pneumonia, septicemia, and meningitis. The discovery that genetic rearrangements in a type I restriction-modification locus can impact gene regulation and colony morphology led to a new understanding of how this pathogen switches from harmless colonizer to invasive pathogen. These rearrangements, which alter the DNA specificity of the type I restriction-modification enzyme, occur across many different pneumococcal serotypes and sequence types and in the absence of all known pneumococcal site-specific recombinases. This finding suggests that this is a truly global mechanism of pneumococcal gene regulation and the need for further investigation of mechanisms of site-specific recombination.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Effects of acarbose and siglitine on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus.

The effects of acarbose and sitagliptin on blood glucose fluctuation and islet ß-cell function in patients with type 2 diabetes mellitus (T2DM) were studied. One hundred and three patients with poorly controlled T2DM with insulin aspart 30 were selected and randomly divided into three groups: group A [continuous subcutaneous insulin infusion (CSII) treatment group], group B (CSII combined with acarbose treatment), group C (CSII combined with sitagliptin treatment). The treatment lasted for two weeks and the clinical indicators in the three groups were measured. The insulin dosage was adjusted according to the blood glucose statuses of the three groups of patients. In the final three days, 72 h of continuous glucose monitoring (CGM) were carried out, and the OGTT test was performed again. The results showed that the MODD (absolute means of daily difference), intra-day blood glucose fluctuation indices [(24 h MBG (mean blood glucose), LAGE (largest amplitude of glycemic excursions) and MAGE (average blood glucose fluctuation)] and postprandial blood glucose fluctuation indices [PGS (postprandial glucose spike), △t, PPGE (postprandial glucose excursion) and T (time) total] in group C and group B were significantly lower than those in group A. Compared with group B, the difference in blood glucose fluctuation indices in group C was not statistically significant (P>0.05). The HOMA-islet (homeostasis model assessment of islet) (CP-DM) index and FC-P (Fasting c-peptide) levels in group C and group B were significantly higher than those in group A (P less than 0.01). The HOMA-IR (CP) index of groups B and C was significantly lower than that of group A (P less than 0.01), and there was no statistically significant difference between groups B and C (P less than 0.05). Sitagliptin combined with intensive insulin pump therapy can reduce blood glucose fluctuation throughout the day, reduce insulin dosage, improve islet B cell function and reduce hypoglycemia better than intensive insulin pump therapy alone.

Genome-wide DNA methylation patterns in coronary heart disease.

BACKGROUND: To better understand the molecular mechanisms of atherosclerosis, we conducted a comparative analysis of DNA methylation patterns in right coronary arteries in the area of advanced atherosclerotic plaques (CAP), great saphenous vein (GSV), and internal mammary artery (IMA) of patients affected by coronary heart disease. METHODS: DNA methylation data (accession number E­GEOD-62867) were divided into three paired groups: CAP vs. IMA, CAP vs. GSV, and IMA vs. GSV. Differentially methylated genes (DMGs) were extracted to analyze the changes in the DMGs in the three different tissues. The gplots package was used for the clustering and heatmap analysis of DMGs. Subsequently, DMG-related pathways were identified using DAVID (Database for Annotation, Visualization and Integrated Discovery) and transcription factors (TFs) were predicted. RESULTS: Based on the filtering criterion of p < 0.05, and a mean beta value difference of ≥0.2, there were 252, 373, and 259 DMGs, respectively, in the CAP vs. IMA, CAP vs. GSV, and IMA vs. GSV groups. Interestingly, the S100A10 gene was hypomethylated in CAP compared with IMA and GSV. Clustering and heatmap analyses suggested that DMGs were segregated into two distinct clusters. Hypermethylated genes in CAP as compared with GSV were only involved in the pathway of fat digestion and absorption, while hypomethylated genes in CAP compared with GSV mainly participated in immune response-associated pathways (cytokine-cytokine receptor interaction, MAPK signaling pathway). CONCLUSION: The DNA methylation differences in vascular tissues of patients with coronary artery disease may provide new insights into the mechanisms underlying the development of atherosclerosis. The functions identified here-cytokine-cytokine receptor interaction, MAPK signaling pathway, DMG (S100A10), and TF (NF-kB)-may serve as potential targets in the treatment of atherosclerosis.

[Impact on the incidence of postoperative ventricular arrhythmias after cardiac resynchronization therapy defibrillator with quadripolar lead].

Objective: To evaluate incidence of postoperative ventricular arrhythmias in patients who received cardiac resynchronization therapy defibrillator (CRT-D ) with left ventricular quadripolar lead. Methods: The patients received CRT-D who had complete follow-up data in Anhui Provincial Hospital from June 2013 to June 2016 were included and divided into quadripolar lead group and bipolar lead group according to the type of left ventricular lead. And ventricular arrhythmia (VA), implantable cardioverter-defibrillator (ICD) shocks treatment, antitachycardia pacing therapy (ATP), and other indicators of the two groups were compared. Prognosis of the two groups was assessed by re-hospitalization for heart failure and cardiac death. Results: Of the 220 patients enrolled in the study, 58 patients were in quadripolar lead group and 162 in bipolar lead group, and there were no significant differences in baseline characteristics between the two groups. The VA episode per patient was not significantly different between the two groups [(0.60±2.38) VA per person vs (0.93±2.24) VA per person, P=0.055]; the quadripolar lead group had significantly lower burden of VA compared with bipolar lead group [(0.22±0.91) per person-year vs (0.46±1.13) per person-year, P=0.044]. Compared with bipolar lead group, there were significant reduction in both the ICD shocks per patient and the burden of ICD shocks in quadripolar lead group: [(0.12±0.36) shocks per person vs (0.23±0.52) shocks per person, P=0.034] and [(0.04±0.17) per person-year vs (0.12±0.46) per person-year, P=0.029], respectively. There were no significant differences between the two groups in both the ATP per patient and the burden of ATP: [(1.07±3.77) ATP per person vs (1.26±3.01) ATP per person, P=0.073] and [(0.38±1.39) per person-year vs (0.63±1.48) per person-year, P=0.058], respectively. And there were no significant differences between the two groups for the survival (P=0.496). Conclusion: Compared with bipolar lead group, the burden of VA could be significantly reduced after CRT-D in the quadripolar lead group.

Protective effect of penehyclidine hydrochloride on lipopolysaccharide-induced acute kidney injury in rat.

We aimed to observe the effect of penehyclidine hydrochloride (PHC) on lipopolysaccharide (LPS)-induced acute kidney injury in rats and expression of tight junction proteins ZO-1 and occludin. Adult male Sprague-Dawley (SD) rats were divided randomly (N = 10) into control group (C), LPS group (LPS), low-dose PHC group (L-PHC), and high-dose PHC group (H-PHC). All rats, except C group, received a vena caudalis injection of 5.0 mg/kg LPS; after 30 min, rats in L-PHC and H-PHC groups received a vena caudalis injection of 0.3 and 0.9 mg/kg PHC. After 24 h, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, serum creatinine (Scr), and blood urea nitrogen (BUN) were detected. Histopathological changes and expression of ZO-1 and occludin were observed in renal tissues. Versus levels of TNF-α (38.5 ± 9.0), IL-1ß (46.3 ± 12.7), Scr (37.2 ± 9.3), and BUN (6.5 ± 1.1) in control group, those in LPS group, TNF-α (159.0 ± 21.3), IL-1ß (130.8 ± 18.7), Scr (98.5 ± 18.2), and BUN (12.8 ± 1.8), increased obviously (P < 0.05), with significantly structural changes and decreases of ZO-1 and occludin. However, TNF-α (111.3 ± 11.6), IL-1ß (78.4 ± 14.3), Scr (51.3 ± 12.5), BUN (8.1 ± 1.2) in H-PHC group, and TNF-α (120.8 ± 14.3), IL-1ß (92.5 ± 19.0), Scr (56.7 ± 14.7), BUN (9.7 ± 1.6) in L-PHC group were obviously decreased (P < 0.05). PHC has protective effects on acute kidney injury in sepsis, including abatement of renal tissue inflammation and functional improvement, potentially by upregulating ZO-1 and occludin.

Insulin and extremity muscle mass in overweight and obese women.

BACKGROUND: Obesity disproportionately affects women, especially those of African descent, and is associated with increases in both fat and muscle masses. OBJECTIVE: Although increased extremity muscle mass may be compensatory to fat mass load, we propose that elevated insulin levels resulting from diminished insulin sensitivity may additionally contribute to extremity muscle mass in overweight or obese women. METHODS: The following measurements were performed in 197 non-diabetic women (57% black, 35% white; age 46±11 years (mean±s.d.), body mass index (BMI) range 25.0-57.7 kg m(-2)): dual-energy X-ray absorptiometry for fat and extremity muscle masses; exercise performance by duration and peak oxygen consumption (VO2 peak) during graded treadmill exercise; fasting insulin and, in 183 subjects, insulin sensitivity index (SI) calculated from the minimal model. RESULTS: SI (range 0.5-14.1 l mU(-1 )min(-1)) was negatively, and fasting insulin (range 1.9-35.6 µU ml(-1)) positively associated with extremity muscle mass (both P<0.001), independent of age and height. Sixty-seven percent of women completed 6 months of participation in a weight loss and exercise program: we found a significant association between reduction in fasting insulin and a decrease in extremity muscle mass (P=0.038), independent of reduction in fat mass or improvement in exercise performance by VO2 peak and exercise duration, and without association with change in SI or interaction by race. CONCLUSIONS: Hyperinsulinemia in overweight or obese women is associated with increased extremity muscle mass, which is partially reversible with reduction in fasting insulin concentration, consistent with the stimulatory effects of insulin on skeletal muscle.

Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women.

UNLABELLED: In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition. INTRODUCTION: Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults. METHODS: BAT volume (ml) and activity (standard uptake value) were determined by 18F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA. RESULTS: Among 24 healthy adults (age 28±1 years, F=10), BAT volumes were 82.4±99.5 ml in women and 49.7±54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4±8.1% (p=0.03), than men. BAT volume correlated positively with total and spine BMD (r2=0.40 and 0.49, respectively, p<0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p<0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11±2% (p=0.02) and 22±2% (p<0.01), respectively. No associations were observed between BAT parameters and BMD in men. CONCLUSIONS: This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.

Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

UNLABELLED: In animals, high fibroblast growth factor 21 (FGF21) states improve insulin resistance but induce bone loss. Whether FGF21 relates to bone mineral density (BMD) is unknown in humans. Contrary to prediction from animal findings, we found higher FGF21 levels associating with greater BMD in women, independent of age and body composition. INTRODUCTION: Recent laboratory studies suggest that FGF21 is involved in reciprocal regulation of bone and energy homeostasis. Systemic administration of FGF21 protects animals from obesity and diabetes but causes severe bone loss, smothering the enthusiasm over FGF21 as a potential antiobesity therapeutic. To date, there is no information on whether FGF21 relates to BMD in humans. We thus studied the relationship between plasma FGF21 levels and BMD in healthy adults. METHODS: Fasting plasma FGF21 levels were measured by enzyme-linked immunosorbent assay and body composition by dual-energy X-ray absorptiometry. RESULTS: Among 40 healthy volunteers (age 32 ± 10 year, 16 women), men had significantly higher lean body mass (p < 0.01) and total BMD (p < 0.05), and lower percent body fat than women (p < 0.01). Median plasma FGF21 levels were not different between the sexes. While there was no association between FGF21 concentrations and body composition in men, FGF21 levels correlated positively with fat mass (p < 0.01) in women. In men, no significant correlation between FGF21 with BMD was observed. However, in women, FGF21 correlated positively with total BMD (R (2) = 0.69, p = 0.003) and spine BMD (R (2) = 0.76, p = 0.001); the correlation remained significant after adjusting for age, ethnicity, and body composition. CONCLUSIONS: This study reveals for the first time a strong positive association between plasma FGF21 levels and BMD in healthy women, suggesting the association between bone loss and high FGF21 states in animals may not be directly translated to humans in physiologic states. We hypothesize that FGF21 may increase bone mass particularly in women through paracrine mechanisms in the bone-adipose interface.

[Improvement of China's legal system for public health emergency management from the perspective of lifecycle management].

A crucial lesson gained through the pandemic preparedness and response to COVID-19 is that all measures for epidemic control must be law-based. The legal system is related not only to public health emergency management per se but also to all aspects of the institutional supporting system throughout the lifecycle. Based on the lifecycle emergency management model, this article analyses the problems of the current legal system and the potential solutions. It is suggested that the lifecycle emergency management model shall be followed to establish a more comprehensive public health legal system and to gather the intelligence and consensus of experts with different expertise, including epidemiologists, sociologists, economists, jurist and others, which will collaboratively promote the science-based legislation in the field of epidemic preparedness and response for the establishment of a comprehensive legal system for public health emergency management and with Chinese characteristics.