Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

Background and Aims:Autoimmune thyroid disease(AITD)are closely associated with metabolic dysregulation,but the causal role of specific metabolites remains unclear.This study aimed to systematically evaluate the causal relationships between approximately 1 400 blood metabolites and two major AITD subtypes-Graves'disease(GD)and Hashimoto's thyroiditis(HT)-using a two-sample Mendelian randomization(MR)approach,to identify potential risk or protective metabolites and provide genetic evidence for mechanistic studies and targeted metabolic interventions.Methods:Summary-level genome-wide association study(GWAS)data for blood metabolites and AITDs were analyzed using inverse-variance weighted MR as the primary method,supplemented by MR-Egger,weighted median,and mode-based methods.Heterogeneity,pleiotropy,and robustness were assessed through Cochran's Q test,horizontal pleiotropy test,and leave-one-out analyses.Results:Forty-nine metabolites showed significant causal associations with GD and 89 with HT.Hexanoylglutamine and ceramide(d18∶1/16∶0)were identified as GD risk factors,while N2,N2-dimethylguanosine and β-hydroxyisovalerylcarnitine were protective.Pregnanediol sulfate and theobromine were associated with increased HT risk,whereas dihomo-linolenate(20:3n3 or n6)and caprylate appeared protective.The α-ketoglutarate/succinate ratio was positively associated with both diseases,suggesting a shared metabolic risk pathway.Conclusion:This MR study provides genetic evidence supporting causal links between multiple blood metabolites and GD or HT.Several metabolites may serve as predictive or protective biomarkers,offering novel insights into the pathophysiology,early screening,and personalized metabolic intervention strategies for AITDs.

Objective To evaluate the clinical efficacy of high-flow nasal cannula oxygen therapy(HFNC)versus non-invasive positive pressure ventilation(NPPV)in elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)accompanied by mild to moderate hypercapnia.Methods The study included 92 AECOPD patients with hypercapnia treated at the second medical center of Chinese PLA General Hospital from August 2021,to October 2023,with 49 in the NPPV group and 43 in the HFNC group.The two groups were compared in terms of 28-day intubation rate,90-day mortality,and arterial blood gases.Results The NPPV group showed a significantly higher 28-day intubation rate compared to the HFNC group(28.57％vs.11.63％,P<0.05),but no significant differences in the 90-day mortality rate(36.73％vs.23.26％,P>0.05).The Kaplan-Meier curve indicated that the HFNC group had a significantly lower 28-day intubation rate compared to the NPPV group(Log-Rank test:χ2=4.257,P=0.039),but no significant difference in 90-day mortality rate(Log-Rank test:χ2=2.596,P=0.107).A Cox proportional hazards model,which incorporated APACHE Ⅱ score and baseline PaCO2,demonstrated that the risk of 28-day intubation in the HFNC group was reduced by 69％as compared to the NPPV group(HR=0.31,95％CI:0.10～0.93,P=0.037),but the risk of 90-day mortality did not show a significant decrease(HR=0.61,95％CI:0.27～1.37,P=0.232).PaCO2 in both groups decreased gradually and pH increased simultaneously.PaCO2,pH,and PaO2 at 2h and 48h against the baseline values did not differ significantly between the two groups(P>0.05).Conclusion In elderly AECOPD patients with mild-to-moderate hypercapnia,HFNC reduces intubation rates compared to NPPV,without increasing mortality,and shows similar improvements in arterial blood gas indicators,making it a suitable respiratory support option.

Objective To evaluate the clinical efficacy of high-flow nasal cannula oxygen therapy(HFNC)versus non-invasive positive pressure ventilation(NPPV)in elderly patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)accompanied by mild to moderate hypercapnia.Methods The study included 92 AECOPD patients with hypercapnia treated at the second medical center of Chinese PLA General Hospital from August 2021,to October 2023,with 49 in the NPPV group and 43 in the HFNC group.The two groups were compared in terms of 28-day intubation rate,90-day mortality,and arterial blood gases.Results The NPPV group showed a significantly higher 28-day intubation rate compared to the HFNC group(28.57％vs.11.63％,P<0.05),but no significant differences in the 90-day mortality rate(36.73％vs.23.26％,P>0.05).The Kaplan-Meier curve indicated that the HFNC group had a significantly lower 28-day intubation rate compared to the NPPV group(Log-Rank test:χ2=4.257,P=0.039),but no significant difference in 90-day mortality rate(Log-Rank test:χ2=2.596,P=0.107).A Cox proportional hazards model,which incorporated APACHE Ⅱ score and baseline PaCO2,demonstrated that the risk of 28-day intubation in the HFNC group was reduced by 69％as compared to the NPPV group(HR=0.31,95％CI:0.10～0.93,P=0.037),but the risk of 90-day mortality did not show a significant decrease(HR=0.61,95％CI:0.27～1.37,P=0.232).PaCO2 in both groups decreased gradually and pH increased simultaneously.PaCO2,pH,and PaO2 at 2h and 48h against the baseline values did not differ significantly between the two groups(P>0.05).Conclusion In elderly AECOPD patients with mild-to-moderate hypercapnia,HFNC reduces intubation rates compared to NPPV,without increasing mortality,and shows similar improvements in arterial blood gas indicators,making it a suitable respiratory support option.

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

Objective:To compare the differences in chemical compositions before and after processing by different processing methods; To optimize the processing method of Atractylodes lancea Rhizoma.Methods:Atractylodes lancea Rhizoma was processed by stir-frying with bran and treating with rice washing water. The volatile and non-volatile components of raw Atractylodes lancea Rhizoma, bran-fried Atractylodes lancea Rhizoma and rice washing water treated Atractylodes lancea Rhizome were qualitatively analyzed by headspace gas chromatography-mass spectrometry (HS-GC-MS) and ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), and the differences in chemical composition before and after processing were compared.Results:The volatile components of the three different products were determined to have 18 common components, such as agarospirol, β-eudesol, etc. In addition, 86 non-volatile components were determined. The peak area response value of atractylodin, the index component prescribed by pharmacopoeia, decreased after processing, but there was little difference in bran stir-frying and rice-washed water frying.Conclusions:Different processing methods have certain effects on the chemical composition of Atractylodes lancea Rhizoma. Among them, the bran-frying method is superior in improving the quality of preparations, reducing production costs and improving production efficiency. The bran-fried product can be used as raw material for preparation production.

【Objective】 To establish strategies for preventing and managing hypoglycemia in children and adolescents with type 1 diabetes, in order to provide a clinical practice basis for reducing the incidence of hypoglycemia and optimizing comprehensive blood sugar management. 【Methods】 All domestic and foreign evidence on the prevention and management of hypoglycemia in children was retrieved until August 2023, including clinical practice guidelines, evidence summaries, best practice information books, expert consensus, systematic reviews, and original studies. 【Results】 This study included 9 articles, comprising 3 practical guidelines, 4 expert consensus articles, 1 clinical decision, and 1 evidence summary, covering 9 aspects ranging from hypoglycemia identification, risk factors, blood sugar monitoring, insulin treatment plans, health education, diet, exercise, and psychological support. It presents a total of 34 pieces of evidence, synthesizing the best evidence from both domestic and international sources on hypoglycemia prevention strategies for children and adolescents with type 1 diabetes. 【Conclusion】 Based on the latest evidence from domestic and global sources, this study systematically illustrates prevention strategies for hypoglycemia in children and adolescents with type 1 diabetes, providing comprehensive evidence and a reliable theoretical basis for raising clinical caregivers′ awareness of hypoglycemia prevention, reducing the risk of hypoglycemia occurrence, and constructing a systematic hypoglycemia prevention and control strategy.

Background A number of studies have shown that heavy metals in atmospheric PM_2.5 have impacts on human health, while studies on the impact of long-term and low-concentration exposure to lead in PM_2.5 on human health are limited. Objective To investigate the pollution characteristics of lead in ambient PM_2.5 and assess its chronic health risks. Methods Daily PM_2.5 concentration data in Jinan from 2014 to 2019 were collected, and the year-by-year trend of PM_2.5 concentration was analyzed. Licheng District (an industrial area) and Shizhong District (a residential area) were elected to install an ambient PM_2.5 monitoring stationrespectively. The sampling instrument was a 100 L·min⁻¹ high-flow PM_2.5 sampler, with a cumulative sampling time of 20-24 h per day, using a quartz fiber filter membrane for lead detection and a glass fiber filter membrane for PM_2.5 determination. The sampling frequency was 7 consecutive days per month from the 10^th to the 16^th (A total of 493 d were sampled and some were missing; 172 d during the heating period and 321 d during the non-heating period). Two PM_2.5 samples were collected in one monitoring site each day. A total of 986 samples were collected in one monitoring site. The lead content in PM_2.5 samples was detected by inductively coupled plasma mass spectrometry. The concentration of PM_2.5 was measured by weighing method. The annual average concentration and enrichment factor of lead in PM_2.5, the change trend of lead content per unit mass of PM_2.5, and the difference between heating period and non-heating period from 2014 to 2019 were estimated. Technical guide for environment health risk assessment of chemical exposure (WS/T 777-2021) was used to assess the health risks of exposure to lead in PM_2.5. Results The average annual concentration of lead in PM_2.5 ranged from 23.2 ng·m⁻³ to 154.7 ng·m⁻³. The average concentration in heating period from 2015 to 2019 was higher than that in non-heating period, and the differences in 2015, 2017, and 2019 were statistically significant (P < 0.01 or 0.001). The enrichment factors ranged from 200 to 1342 in 2014 to 2019. The average enrichment factors in heating period in 2015, 2017, and 2018 was higher than those in non-heating period, and the difference was statistically significant (P < 0.05 or 0.001). The lead contents per unit mass of PM_2.5 ranged from 493 ng·mg⁻¹ to 1944 ng·mg⁻¹, and the differences between heating period and non-heating period in 2014, 2017, and 2018 were statistically significant (P < 0.05 or 0.001). The average annual concentration and enrichment factor of lead in PM_2.5 showed a downward trend, and thus the lead content per unit mass of PM_2.5 also decreased. From 2014 to 2019, the carcinogenic risk of lead in PM_2.5 in Jinan ranged from 1.69×10⁻⁸ to 2.45×10⁻⁶, showing a significant downward trend year by year, and the 95^th percentile decreased by 3%-46% from the previous year. The carcinogenic risk level of lead was reduced to an acceptable level (<1×10⁻⁶) after 2017. Conclusion From 2015 to 2019, lead concentration and enrichment factor in PM_2.5 increase during heating period compared with non-heating period, but it is not completely consistent of lead content in PM_2.5 per unit mass. From 2014 to 2016, exposure to lead in PM_2.5 may elevate carcinogenic risk to human. After 2017, the carcinogenic risks of exposure to lead in PM_2.5 are at an acceptable level.

Objective:To investigate the effect of follicular size on the clinical outcomes of frozen-thawed embryo transfer induced by human chorionic gonadotropin (hCG) of natural cycles on ovulation.Methods:Clinical data of 427 cycles of frozen-thawed single blastocyst transfer in Nanjing Drum Tower Hospital from January 2016 to December 2019 were retrospectively analyzed. The patients were divided into 15-16 mm group (15≤diameter≤16 mm, n=66), 16-17 mm group (1620 mm group (diameter>20 mm, n=26), according to the maximum follicle diameter on the induction day of hCG ovulation induction. The estradiol and luteinizing hormone (LH) levels, and clinical pregnancy rate, abortion rate and live birth rate were compared in five groups. Results:There were statistically significant differences in estradiol and LH levels among the five groups on the day of hCG induction (all P<0.05). Estradiol levels in 15-16 mm group to >20 mm group gradually increased on the day of hCG induction, and estradiol level in 15-16 mm group was significantly lower than those in 17-18 mm group, 18-20 mm group and >20 mm group (median: 1 002.3 vs 1 103.3 vs 1 171.2 vs 1 539.0 pmol/L), with statistical significances ( P=0.034, P<0.001, P=0.002). On the day of hCG induction, LH levels in 15-16 mm group to >20 mm group showed a decreasing trend, and LH level in 15-16 mm group was significantly higher than those in 17-18 mm group and >20 mm group (median: 37.73 vs 28.24 vs 24.11 U/L), with statistically significant differences ( P=0.007, P=0.006). There were no significant differences in clinical pregnancy rate, abortion rate and live birth rate in 15-16 mm group to >20 mm group (all P>0.05). Conclusion:In the natural cycle protocol of hCG induced ovulation, the small follicle group could achieve similar clinical outcomes compared with normal sized follicles in the single blastocyst transfer of frozen-thawed embryos.