Osteoporosis is a systemic disease characterized by imbalanced bone metabolism and destruction of bone microstructure, with reduced bone density, decreased bone quality, and significantly increased risk of fracture as its hallmarks. At present, osteoporosis is primarily diagnosed through bone density measurement. However, this method has low sensitivity and is challenging for the early diagnosis of osteoporosis. We analyzed osteoporosis-related metabolomics studies based on blood, urine, and fecal samples, as well as the application of multi-omics approaches in elucidating its pathogenesis. Evidence suggests that metabolomics can detect metabolic alterations prior to measurable changes in bone mineral density, offering promising avenues for early osteoporosis detection. Blood-based metabolomics studies indicate that amino acid metabolism dysregulation is a key feature of osteoporosis. Specifically, glycine, glutamine, lysine, and hydroxyproline exhibit negative correlations with bone mineral density, whereas tryptophan, branched-chain amino acids, and arginine show positive associations. Lipid metabolism disturbances are characterized by increased levels of phosphatidylcholine, phosphatidylethanolamine, and triglycerides, alongside decreased levels of sphingomyelin and carnitine. Fecal metabolomics studies highlight the significance of the "gut-bone axis" in osteoporosis, where gut microbiota dysbiosis influences bone metabolism through modulation of arginine and proline metabolism and aminoacyl-tRNA biosynthesis pathways. Multi-omics approaches integrate metabolomics, genomics, proteomics, and other omics data to provide a more comprehensive understanding of osteoporosis' molecular mechanisms, enabling the identification of key biomarkers and therapeutic targets. Metabolomics holds considerable potential for early diagnosis, while multi-omics integration offers novel insights into the complex pathophysiological mechanisms underlying osteoporosis. As detection technologies and analytical methods continue to advance, omics-based strategies are expected to play a pivotal role in the development of precision medicine for osteoporosis.

Osteoporosis is a systemic disease characterized by imbalanced bone metabolism and destruction of bone microstructure, with reduced bone density, decreased bone quality, and significantly increased risk of fracture as its hallmarks. At present, osteoporosis is primarily diagnosed through bone density measurement. However, this method has low sensitivity and is challenging for the early diagnosis of osteoporosis. We analyzed osteoporosis-related metabolomics studies based on blood, urine, and fecal samples, as well as the application of multi-omics approaches in elucidating its pathogenesis. Evidence suggests that metabolomics can detect metabolic alterations prior to measurable changes in bone mineral density, offering promising avenues for early osteoporosis detection. Blood-based metabolomics studies indicate that amino acid metabolism dysregulation is a key feature of osteoporosis. Specifically, glycine, glutamine, lysine, and hydroxyproline exhibit negative correlations with bone mineral density, whereas tryptophan, branched-chain amino acids, and arginine show positive associations. Lipid metabolism disturbances are characterized by increased levels of phosphatidylcholine, phosphatidylethanolamine, and triglycerides, alongside decreased levels of sphingomyelin and carnitine. Fecal metabolomics studies highlight the significance of the "gut-bone axis" in osteoporosis, where gut microbiota dysbiosis influences bone metabolism through modulation of arginine and proline metabolism and aminoacyl-tRNA biosynthesis pathways. Multi-omics approaches integrate metabolomics, genomics, proteomics, and other omics data to provide a more comprehensive understanding of osteoporosis' molecular mechanisms, enabling the identification of key biomarkers and therapeutic targets. Metabolomics holds considerable potential for early diagnosis, while multi-omics integration offers novel insights into the complex pathophysiological mechanisms underlying osteoporosis. As detection technologies and analytical methods continue to advance, omics-based strategies are expected to play a pivotal role in the development of precision medicine for osteoporosis.

Objective:To study the the mechanism of action of Huanglong Mixture in the treatment of cough variant asthma (CVA) in children based on the IL-4/signal transduction and activator of transcription 6 (STAT6) signaling pathway using network pharmacology methods, molecular docking techniques, and in vitro cell experiments.Methods:The components and targets of various TCM components in Huanglong Mixture were searched in TCMSP database, HERB database and literature, and the disease targets of CVA were found in Gene Cards database, OMIM database, DrugBank database and PharmGkb database. The STRING database was used to construct the protein-protein interaction network, and Cytoscape 3.9.1 was used for topology analysis to screen out the core targets. The disease-drug-component-target network was constructed to screen out the core components. The KEGG enrichment analysis and GO enrichment analysis of the intersection targets were performed using Metascape software. PDB protein database, PubChem, Autodock and R language were used for molecular docking verification of core targets and core drug components. Finally, rat primary airway smooth muscle cells were cultured, modeled with interleukin-4 (IL-4), and p-STAT6 expression in the cytoplasm and nucleus was detected by Western blot.Results:A total of 122 effective components were obtained, including quercetin, kaempferol, luteolin and so on. The core targets included JUN, ESR1, TP53, MYC, HIF1, etc. GO enrichment analysis involved biological processes such as response to external stimuli, response to oxygen levels, positive regulation of protein phosphorylation, and regulation of cellular stress response. KEGG enrichment analysis showed that the main pathways of Huanglong Mixture in treating CVA included advanced glycation end product-glycation end product receptor (AGE-RAGE) signaling pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Janus kinase/signal transduction activation factor (JAK-STAT) signaling pathway. Molecular docking found that the core targets and core drug components had good combination. Cell experiments also confirmed that Huanglong Mixture could inhibit p-STAT6 entering the nucleus.Conclusions:The effective components and targets of Huanglong Mixture in the treatment of CVA are successfully predicted. The mechanism of Huanglong Mixture in the treatment of children with CVA may be related to the inhibition of IL-4/STAT6 signaling pathway.

Objective To analyze the distribution characteristics of abnormal karyotypes of fetal sex chromosome aneuploidy(SCA)and pregnancy outcomes in 101 fetal cases.Methods A retrospective study was conducted among 7 821 pregnant women who underwent successfully prenatal karyotyping diagnosis at Guangxi Zhuang Autonomous Region People's Hospital from January 2016 to December 2021.All women received amniotic fluid cell culture karyotype analysis and copy number variation sequencing(CNV-seq)detection and 101 cases of SCA detected were analyzed.Results A total of 101 cases were detected by SCA,with a detection rate of 1.29％.Among them,Klinefelter syndrome accounted for 33.66％,superestrogenism syndrome accounted for 17.82％,superandrogenic syndrome accounted for 12.87％,turner syndrome accounted for 10.89％,other aneuploidy abnormalities[including 48,XXXY:1 case;69,XXY(80％)/68,XXY,-22(20％):1 case]accounted for 1.98％,and chimerism accounted for 22.77％.The prenatal indications for 101 cases of SCA were as follows:age ≥ 35 years,high/critical risk of serum biochemical screening,fetal ultrasound abnormalities,abnormalities in non-invasive prenatal testing(NIPT),history of adverse pregnancy and childbirth and other reasons(1 case of cerebral palsy in pregnant women and 4 cases of bilateral thalassemia)accounted for 53.47％(54/101),4.95％(5/101),17.82％(18/101),51.49％(52/101),12.87％(13/101),4.95％(5/101),respectively.Partial cases had multiple prenatal diagnostic indications.Meanwhile,23 fetuses diagnosed with sex chromosome chimerism,of which 22 cases were validated by karyotype and CNV seq,11 pregnant women chose to terminate their pregnancy,with the rest chose to continue pregnancy.Conclusion The combination of prenatal karyotype diagnosis,serological testing,prenatal ultrasound and other prenatal screening methods can help improve the detection rate of SCA,while CNV-seq can provide more clinical evidence for genetic counseling of pregnant women with sex chromosome chimerism.

Extracellular vesicles (EVs) are communication vectors between cells and organs, which have been demonstrated new potential role in the pathogenesis, diagnosis, and treatment of kidney diseases. This paper describes the role of EVs in intercellular and inter organ communication in diabetic nephropathy by reviewing the biological properties of EVs, EVs-mediated organ-organ crosstalk, cell-cell crosstalk in diabetic nephropathy, and the role of EVs in the diagnosis and treatment of renal diseases. These insights aim to provide a theoretical basis for a more comprehensive understanding of the role of EVs in the pathogenesis and progression of diabetic nephropathy.

Extracellular vesicles (EVs) are communication vectors between cells and organs, which have been demonstrated new potential role in the pathogenesis, diagnosis, and treatment of kidney diseases. This paper describes the role of EVs in intercellular and inter organ communication in diabetic nephropathy by reviewing the biological properties of EVs, EVs-mediated organ-organ crosstalk, cell-cell crosstalk in diabetic nephropathy, and the role of EVs in the diagnosis and treatment of renal diseases. These insights aim to provide a theoretical basis for a more comprehensive understanding of the role of EVs in the pathogenesis and progression of diabetic nephropathy.

OBJECTIVE To provide the suggestions for improving t he enthusiasm of the public to report adverse drug reactions （ADRs），promoting pharmaceutical manufacturers to improve the smoothness of ADR reporting channels by the public and the enthusiasm of assuming the main responsibility for drug safety ，and to provide reference for the performance of drug safety supervision by regulatory departments in China. METHODS Taking 180 pharmaceutical manufacturers that had entered the top 1 000 in the world as the objects ，the questionnaire was prepared to investigate the smoothness of ADR reporting channels through 4 channels：contact number ，e-mail，official website and new media （including Wechat and microblog ） of enterprise . The questionnaire involved the establishment of public reporting channels ，the records and the feedback of enterprises. The existing problems were analyzed and suggestions were put forward. RESULTS & CONCLUSIONS More than 70％ of pharmaceutical manufacturers in China had established the channels for reporting ADR by the public ，which were mainly regular channels such as contact numbers and e-mail ，and each channel had the phenomenon that ADR information couldn ’t be reported. More than 60％ of the public channels established by manufactures lacked inquiry and supplement for the miss ing part of th e reported information ； only 24 pharmaceutical manufacturers provided feedback on ADR information ，and the feedback contents were monotonous. gywf2021-11It is suggested that pharmaceutical manufacturers should pay more attention to ADR monitoring among the public ，consider increasing multiple reporting channels while ensuring the smoothness of channels ，strengthen the training of employee ’s information collection ability to improve the quality of information ，timely feed back the ADR information reported by the public ， and increase the feedback content concerned by the public.

OBJECTIVE To provide re ference for accurate measurem ent of population health status ，pharmacoeconomic evaluation and guidance of health resource allocation. METHODS Using quota and convenient sampling ，five administrative villages were selected from the rural areas under the jurisdiction of Liuzhi special zone ，Qianxi city and Jianhe county of Guizhou province from July to September 2020. Based on the gender and age ratio quota of rural population in the results of the national census，330 respondents were selected for questionnaire survey. The contents of the questionnaire included the self-made scale containing sociodemographic characteristics and general health information ，five-level EuroQoL five-dimension questionnaire （EQ-5D-5L，hereinafter referred to as the “new dimension scale ”）with cognitive dimensions （including attention ，memory， computing ability and learning ability ）and mini-mental state examination （MMSE）. The effects of reliability ，validity and new dimensions of new dimension scale on respond ents’quality of life were investigate ，and its measurement characteristics were verified；the application value of it in pharmacoeconomic hy_cheer@126.com evaluation and guiding the allocation of health resources were explored. RESULTS A total of 330 questionnaires weredistributed，320 were recovered and 320 were effective. The recovery rate and effective rate were 96.97％ and 100％ respectively. The ceiling effect of new dimension scale was 13.44％，the split-half reliability was 0.821，and the overall Cronbach ’s α was 0.852. Exploratory factor analysis showed that the new dimension scale was loaded with physiological ，cognitive and psychological factors ，and the cumulative contribution rate was 69.35％. The correlation coefficient between the new dimension and the dimension of MMSE scale were 0.19-0.61，showing a moderate or medium to strong correlation （P＜0.01）. Compared with EQ- 5D-5L，after adding each dimension ，the interpretation ability of the regression model was improved by 5.00％-17.50％. CONCLUSIONS The new dimension scale has high feasibility ，good reliability and validity ，significantly reduces the ceiling effect of EQ- 5D-5L，has higher sensitivity to the evaluation of people ’s quality of life，and can better evaluate the quality of life of rural population. It is suggested that it can be applied for quality of life evaluation，intervention effect analysis and related economic evaluation.

Objective:To investigate whether the real-world marital status is a factor affecting the survival of patients with early stage breast cancer.Methods:According to the data of 62 845 patients with early stage (T 1-2N 0M 0) breast cancer who received treatment from January 2012 to December 2015 in the Surveillance, Epidemiology and End Results (SEER) database, univariate survival analysis for 7 factors including age, race, surgery, T stage, tumor differentiation, molecular type and marital status was performed by Kaplan-Meier method. The 5-year cancer specific survival (5-CSS) rate was calculated. Multivariate Cox proportional hazards model was used to analyze the death risk of patients with different marital status (married, unmarried and bad marriage). Results:Univariate analysis showed that 7 factors were correlated with the survival of patients with early stage breast cancer (all P < 0.001). Multivariate analysis showed that marital status was an independent factor affecting the survival of patients, and the death risk of unmarried patients and patients with bad marriage was 2.014 times (95% CI 1.714-2.367, P < 0.001) and 2.559 times (95% CI 2.254-2.905, P < 0.001) higher than that of married patients, respectively. In tumor differentiation, molecular type, T stage and race subgroups, univariate analysis showed that the rates of 5-CSS in married patients were higher than those in unmarried patients and patients with bad marriage (all P < 0.001); multivariate analysis showed that the risk of death in patients with bad marriage (except undifferentiated type) was higher than that in married patients (all P < 0.001), and the risk of death in unmarried patients (except undifferentiation, Luminal B type, black and other races) was also higher than that in married patients (all P < 0.01). Conclusions:Marital status is one of the factors influencing the survival of patients with early stage breast cancer.

Objective:To compare the dosimetric difference between intensity-modulated photon radiaotherapy (IMRT) planning and intensity-modulated proton radiotherapy (IMPT) planning for glioma.Methods:The clinical data of 15 glioma patients who underwent IMRT in ion medical center of the First Affiliated Hospital of USTC from November 2020 to April 2022 were retrospectively analyzed. IMRT planning and IMPT planning were designed for the image of each patient in the therapy planning system. Main dosimetric parameters were compared including plan target volume (PTV), coverage index (CI), dose homogeneity index (HI), and maximal dose (D max) and mean dose (D mean) of organs at risk between both plans. Results:There were no significant differences between IMRT planning and IMPT planning in terms of D max and D mean of PTV1 and PTV2, CI and HI (all P > 0.05). Compared with IMRT planning, brainstem D mean [6.92 GyE (0.09 GyE, 12.58 GyE) vs. 24.41 GyE (2.59 GyE, 34.18 GyE)], left optic nerve D max [0.78 GyE (0.04 GyE, 25.18 GyE) vs. 20.42 GyE (6.38 GyE, 37.17 GyE)], left optic nerve D mean [0.10 GyE (0.01 GyE, 11.63 GyE) vs. 9.74 GyE (2.99 GyE, 20.87 GyE)], right optic nerve D mean [1.57 GyE (0.13 GyE, 14.90 GyE) vs. 14.08 GyE (2.66 GyE, 23.67 GyE)], left len D max [0 GyE (0 GyE, 2.91 GyE) vs. 4.84 GyE (1.42 GyE, 5.48 GyE)], left len D mean [0 GyE (0 GyE, 1.73 GyE) vs. 3.84 GyE (1.25 GyE, 4.30 GyE)], right len D max [0.25 GyE (0.04 GyE, 4.55 GyE) vs. 4.28 GyE (1.58 GyE, 5.84 GyE)], right len D mean [0.16 GyE (0.01 GyE, 1.95 GyE) vs. 3.73 GyE (1.04 GyE, 4.86 GyE)], pituitary D max [6.97 GyE (0.18 GyE, 39.70 GyE) vs. 36.60 GyE (2.74 GyE, 45.19 GyE)], pituitary D mean [1.36 GyE (0.06 GyE, 13.85 GyE) vs. 24.74 GyE (2.42 GyE, 32.80 GyE)], hippocampus D max [5.10 GyE (0.24 GyE, 26.52 GyE) vs. 35.83 GyE (5.03 GyE, 46.11 GyE)], hippocampus D mean [0.36 GyE (0.04 GyE, 25.65 GyE) vs. 18.79 GyE (2.37 GyE, 28.10 GyE)] in IMPT planning were lower, and the differences were statistically significant (all P < 0.05). There were no statistical differences in brainstem D max [51.98 GyE (0.66 GyE, 53.43 GyE) vs. 53.29 GyE (3.87 GyE, 53.48 GyE)], right optic nerve D max [9.60 GyE (0.01 GyE, 43.32 GyE) vs. 25.37 GyE (3.45 GyE, 41.25 GyE)] of both plans (all P > 0.05). Conclusion:In the radiotherapy for glioma, IMRT and IMPT can meet the dose demand in clinic. Furthermore, IMPT planning can protect organs at risk and reduce radiation dose in hippocampus, brainstem, optic nerve, lens and pituitary.