Brown adipose tissue(BAT), a metabolically active organ, not only plays a pivotal role in thermogenesis, but also exerts endocrine effects that regulate both its own metabolic processes and the function of various other organ systems. These effects are primarily mediated by brown adipose tissue-derived factors, or batokines. Recent advances in the understanding of batokine types, target organs, and underlying mechanisms have highlighted their significant role in the crosstalk between BAT and other organs. This review focuses on the various batokines secreted by BAT and their involvement in regulating interactions with key target organs such as the liver, cardiovascular system, skeletal muscle, and nervous system. By examining the specific functions and molecular mechanisms of these factors, this review aims to offer novel insights and suggest potential research directions for the prevention and treatment of related metabolic diseases.

Type 2 diabetes mellitus(T2DM)has emerged as a significant public health challenge and a con-siderable threat to human well-being due to its chronic nature.Consequently,it cannot be overlooked.In response to this pressing issue,scientific weight loss treatments have demonstrated their effectiveness as a coping strategy.Particularly,for patients in the early stages of the disease with preserved pancreatic islet function and obesity,weight loss treatment has been shown to significantly enhance their glucose tolerance and ameliorate metabolic disorders.Ongoing research has led to a growing body of evidence regarding the mechanisms and clinical data supporting the use of weight loss therapy in miti-gating type 2 diabetes.This paper aims to evaluate the impact of weight loss therapy on the major metabolic organs of the body,such as the liver,pancreas,skeletal muscle,and adipose tissue,and to delve into the physiological and molecular mechanisms involved in the remission of T2DM.

To analyze the disease burden, temporal trends, and attributable risk factors of early-onset female breast cancer (EOBC) in China and globally from 1990 to 2021.

[Purpose]To analyze the disease burden of malignant tumors and its changing trends in Chinese and global non-smoking female population from 1990 to 2021.[Methods]Data of mortality and disability-adjusted life year(DALY)due to malignant tumors for Chinese and global non-smoking female malignant tumors from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021(GBD 2021),and the average annual percentage change(AAPC)were calculated using Joinpoint regression model.[Results]From 1990 to 2021,the number of deaths for malignant tu-mors in Chinese non-smoking female population increased from 13.7 1×104 to 26.8 1×104,with a higher increased trend compared with the global(China:AAPC=2.19％,95％CI:2.06％～2.33％;Global:AAPC=1.92％,95％CI:1.80％～2.04％,P=0.003);the age-standardized mortality rate decreased from 32.42/105 to 24.58/105,with a higher decreased trend compared with the global(China:AAPC=-0.88％,95％CI:-1.00％～-0.76％;Global:AAPC=-0.59％,95％CI:-0.68％～-0.51％,P＜0.001).From 1990 to 2021,the DALY for malignant tumors in Chinese non-smoking female population increased from 412.96×104 to 691.20×104 person-years,with a similar changing trend compared with the global(China:AAPC=1.68％,95％CI:1.56％～1.81％,Global:AAPC=1.63％,95％CI:1.52％～1.75％,P=0.536);the age-standardized DALY rate in Chinese non-smoking female population decreased from 889.58/105 to 642.65/105,with a higher decreased trend compared with the global(China:AAPC=-1.04％,95％CI:-1.15％～-0.92％;Global:AAPC=-0.69％,95％CI:-0.78％～-0.61％,P＜0.001).The top five malignant tumors of high age-standardized mor-tality rate in Chinese non-smoking female population in 2021 were tracheal,bronchus and lung cancer,colon and rectum cancer,cervical cancer,breast cancer,and liver cancer.The top five malignant tumors of high age-standardized mortality rate globally in 2021 were cervical cancer,colon and rectum cancer,breast cancer,tracheal,bronchus and lung cancer,and pancreatic cancer.The age-standardized mortality rate and DALY rate of breast cancer,liver cancer,pan-creatic cancer and corpus cancer showed overall upward trends(all P＜0.05).[Conclusion]From 1990 to 2021,the number of deaths and DALY of malignant tumors in Chinese and global non-smoking female population showed overall increased trends,and age-standardized mortality rate and DALY rate showed overall decreased trends.In future,more targeted cancer prevention measures are needed to reduce the disease burden of malignant tumors in non-smoking female population.

Type 2 diabetes mellitus(T2DM)has emerged as a significant public health challenge and a con-siderable threat to human well-being due to its chronic nature.Consequently,it cannot be overlooked.In response to this pressing issue,scientific weight loss treatments have demonstrated their effectiveness as a coping strategy.Particularly,for patients in the early stages of the disease with preserved pancreatic islet function and obesity,weight loss treatment has been shown to significantly enhance their glucose tolerance and ameliorate metabolic disorders.Ongoing research has led to a growing body of evidence regarding the mechanisms and clinical data supporting the use of weight loss therapy in miti-gating type 2 diabetes.This paper aims to evaluate the impact of weight loss therapy on the major metabolic organs of the body,such as the liver,pancreas,skeletal muscle,and adipose tissue,and to delve into the physiological and molecular mechanisms involved in the remission of T2DM.

[Purpose]To analyze the disease burden of malignant tumors and its changing trends in Chinese and global non-smoking female population from 1990 to 2021.[Methods]Data of mortality and disability-adjusted life year(DALY)due to malignant tumors for Chinese and global non-smoking female malignant tumors from 1990 to 2021 were extracted from the Global Burden of Disease Study 2021(GBD 2021),and the average annual percentage change(AAPC)were calculated using Joinpoint regression model.[Results]From 1990 to 2021,the number of deaths for malignant tu-mors in Chinese non-smoking female population increased from 13.7 1×104 to 26.8 1×104,with a higher increased trend compared with the global(China:AAPC=2.19％,95％CI:2.06％～2.33％;Global:AAPC=1.92％,95％CI:1.80％～2.04％,P=0.003);the age-standardized mortality rate decreased from 32.42/105 to 24.58/105,with a higher decreased trend compared with the global(China:AAPC=-0.88％,95％CI:-1.00％～-0.76％;Global:AAPC=-0.59％,95％CI:-0.68％～-0.51％,P＜0.001).From 1990 to 2021,the DALY for malignant tumors in Chinese non-smoking female population increased from 412.96×104 to 691.20×104 person-years,with a similar changing trend compared with the global(China:AAPC=1.68％,95％CI:1.56％～1.81％,Global:AAPC=1.63％,95％CI:1.52％～1.75％,P=0.536);the age-standardized DALY rate in Chinese non-smoking female population decreased from 889.58/105 to 642.65/105,with a higher decreased trend compared with the global(China:AAPC=-1.04％,95％CI:-1.15％～-0.92％;Global:AAPC=-0.69％,95％CI:-0.78％～-0.61％,P＜0.001).The top five malignant tumors of high age-standardized mor-tality rate in Chinese non-smoking female population in 2021 were tracheal,bronchus and lung cancer,colon and rectum cancer,cervical cancer,breast cancer,and liver cancer.The top five malignant tumors of high age-standardized mortality rate globally in 2021 were cervical cancer,colon and rectum cancer,breast cancer,tracheal,bronchus and lung cancer,and pancreatic cancer.The age-standardized mortality rate and DALY rate of breast cancer,liver cancer,pan-creatic cancer and corpus cancer showed overall upward trends(all P＜0.05).[Conclusion]From 1990 to 2021,the number of deaths and DALY of malignant tumors in Chinese and global non-smoking female population showed overall increased trends,and age-standardized mortality rate and DALY rate showed overall decreased trends.In future,more targeted cancer prevention measures are needed to reduce the disease burden of malignant tumors in non-smoking female population.

Brown adipose tissue(BAT), a metabolically active organ, not only plays a pivotal role in thermogenesis, but also exerts endocrine effects that regulate both its own metabolic processes and the function of various other organ systems. These effects are primarily mediated by brown adipose tissue-derived factors, or batokines. Recent advances in the understanding of batokine types, target organs, and underlying mechanisms have highlighted their significant role in the crosstalk between BAT and other organs. This review focuses on the various batokines secreted by BAT and their involvement in regulating interactions with key target organs such as the liver, cardiovascular system, skeletal muscle, and nervous system. By examining the specific functions and molecular mechanisms of these factors, this review aims to offer novel insights and suggest potential research directions for the prevention and treatment of related metabolic diseases.

OBJECTIVE To investigate the impact of the methionine synthase reductase （MTRR） rs10380 C＞T gene polymorphism on methotrexate （MTX） plasma concentration， adverse drug reaction， and prognosis in children with intracranial tumors. METHODS Peripheral blood was collected from children with intracranial tumors， and genomic DNA was extracted. The MTRR rs10380 C＞T genotype was analyzed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The association of the MTRR rs10380 C＞T gene polymorphism with the ratio of MTX plasma concentration to dose （C/D ratio）， adverse drug reaction， tumor recurrence， and metastasis was analyzed. Bioinformatics analysis was used to explore the association of the rs10380 genotype and MTRR gene expression and its possible mechanisms. RESULTS A total of 75 children were included in the study. The distribution frequencies of the wild-type CC genotype and C allele of rs10380 were 62.67% and 81.33%， respectively， while the distribution frequencies of the variant CT genotype and T allele were 37.33% and 18.67%， respectively， which were in accordance with Hardy-Weinberg equilibrium（P＞0.05）. The incidence of electrolyte disorders （51.06%） and tumor metastasis rate （57.45%） in children with the CC genotype were significantly higher than those with the CT genotype （P＜0.05）. No significant differences were observed in the 24-hour and 42-hour C/D ratios and recurrence rates between the two genotypes of children （P＞0.05）. Bioinformatics analysis showed that MTRR protein mainly works in conjunction with 10 proteins， including MMAA， and was involved in various biological processes such as sulfur amino acid biosynthesis. CONCLUSIONS The MTRR rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.

Objective:To investigate mechanisms whereby phospholipase D1(PLD1)promotes pancreatic ductal adenocarcinoma(PDAC)progression.Methods:Targets were identified by screening the Genomic Spatial Event(GSE)database for genes differentially expressed in metastatic and primary tumors.Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas.Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining.The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data.The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1.The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice.Growth of primary tumors and liver metastases was monitored using bioluminescent imaging.The role of PLD1 in tumor progression was assessed using western blotting,transwell migration and scratch assays,and PLD1 enzyme-mutation cell lines.Downstream PLD1 target genes were identified using quantitative real-time PCR(qPCR),transcriptome sequencing,and response blocking.The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.Results:PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis,PLD1 expression was associated with diminished survival in PDAC patients;PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver(P<0.01);Treating the SW1990 cell line with PA and choline(PLD1 pathway products)did not restore loss of PDAC cell migration and invasion ability.Transwell and scratch assays in KRM,a PLD1 catalytic-mutation cell line,suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1.qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1.A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1.A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.Conclusion:PLD1 upregulates FSTL1 expression,promotes epithelial-mesenchymal transition of tumor cells,and enhances PDAC metastasis.Thus,PLD1 blockade could inhibit PDAC progression.