Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.
Female ; Humans ; Papillomavirus Infections/diagnosis* ; Retrospective Studies ; Uterine Cervical Neoplasms/pathology* ; Prognosis ; Oncogene Proteins, Viral/genetics* ; Human Papillomavirus Viruses ; Adenocarcinoma/pathology* ; RNA, Messenger/genetics* ; Papillomaviridae/genetics* ; RNA, Viral/genetics*

Objective: To investigate the current situation of obesity and related metabolic abnormalities among preschool children, so as to provide theoretical support for future intervention. Methods: A cohort of 3 952 children, born in Tianjin and enrolled in the kindergarten from September 2017 to October 2018, were selected to conduct a baseline survey and a three-year follow-up (questionnaire survey, physical examination and laboratory testing). At the same time, a two-way cohort study was conducted to retrospectively collect maternal prenatal examination, delivery and regular physical examination information of children from birth to preschool age from Tianjin Maternal and Child Health Information System. Results: A total of 3 935, 3 654 and 2 739 children completed the follow up in the primary, middle and senior classes of kindergarten respectively. The height and weight of pre-school children increased with age, while the percentage of body fat decreased with age ( β-trend =-0.74, P <0.01). During three-year follow up, height, weight and body mass index of boys were higher than girls (P<0.05), while the percentage of body fat was lower than girls (primary class: 17.5%,18.5%; middle class: 16.4%,17.2%; senior class: 16.1%,17.1%, P <0.05). The detection rate of overweight (including obesity) and obesity increased with age( χ 2 trend were 15.51,38.72, P <0.05). The total detection rate of obesity increased from 5.4% at the baseline level to 9.6%. Laboratory test results showed that the detection rates of fasting blood glucose of boys were higher than that of girls in primary class, but blood lipid abnormalities were in the opposite (glucose: 7.7%, 4.8 %; lipid: 23.8% , 27.7%)( χ 2=12.01, 6.63, P <0.05). Conclusion The study has established a large growth cohort starting from the early embryonic stage, which will help to establish the strategies to promote children s health and prevent obesity and chronic diseases from multidimensional perspectives.

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .
B-Lymphocytes ; Graft vs Host Disease ; HLA Antigens/genetics* ; Haplotypes ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Leukemia, B-Cell/complications* ; Leukemia, Lymphocytic, Chronic, B-Cell/complications* ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Recurrence ; Retrospective Studies ; Siblings

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Gene Expression ; Genes, ras ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Oncogene Fusion ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Retrospective Studies ; Young Adult

Objective: To analyze the spatiotemporal distribution of life expectancy (LE) and health-adjusted life expectancy (HALE) in Guangzhou from 2010 to 2019, and quantize the comprehensive impact of different causes and sequelae on health. Methods: The LE, HALE, and cause-excluded health adjusted life expectancy (CEHALE) were estimated using cause-of-death surveillance datasets from Guangzhou Municipal Center for Disease Control and Prevention from 2010 to 2019 and open data from the Global Burden of Disease Study. Joinpoint log-linear regression model was used to analyze the temporal trend and described spatial distribution. Results: In 2019, the LE in residents in Guangzhou was 82.9 years (80.1 years in men and 85.9 years in women), and the HALE was 75.6 years (74.0 years in men and 77.3 years in women). Compared with the urban fringe, the central urban area had higher LE and HALE, and the differences between LE and HALE were small. The LE and HALE in Guangzhou showed an increasing trend from 2010 to 2019. The LE increased by 2.8 years (AAPC=0.4, 95%CI: 0.3-0.4), with the increase of 2.8 years in men and 2.9 years in women. The HALE increased by 2.4 years (AAPC=0.3, 95%CI: 0.3-0.4), with the increase of 2.5 years in men and 2.2 years in women. The median healthy life lost due to communicable, maternal, neonatal, and nutritional diseases was 6.2 years (AAPC=-4.2, 95%CI: -5.3--3.1), while the median healthy life lost due to non-communicable diseases was 14.7 years (AAPC=1.6, 95%CI: 0.9-2.3), the median healthy life expectancy reduced by injury was 6.3 years (AAPC=-3.5, 95%CI: -4.5--2.6). Musculoskeletal disorders, skin and subcutaneous diseases, cardiovascular diseases, nutritional deficiencies, diabetes and kidney diseases were the top five diseases causing healthy life expectancy loss. Conclusion: The LE and HALE in residents in Guangzhou increased steadily from 2010 to 2019, but the quality of life in the urban fringe was lower than that of the central urban area. Non-communicable diseases were the leading causes of healthy life expectancy loss. Health policies and prevention measures should be developed according to area specific characteristics, and social medical resources should be rationally allocated to key diseases to reduce their disease burden.
Cost of Illness ; Female ; Health Status ; Humans ; Infant, Newborn ; Life Expectancy ; Male ; Noncommunicable Diseases ; Quality of Life

OBJECTIVE: To explore the improvement effect of CXC chemokine receptor 4 (Cxcr4) gene-modified bone marrow mesenchymal stem cell (BMSC)-derived exosomes on aplastic anemia (AA), and make a preliminary exploration of the mechanism. METHODS: Mouse BMSCs were isolated and cultured, then infected by recombinant lentivirus carrying Cxcr4 gene. The expression of green fluorescence was observed through fluorescence microscope, the expression of Cxcr4 mRNA was detected by real-time fluorescence quantitative PCR, and the BMSC-derived exosomes modified with Cxcr4 gene were extracted. Mouse models of AA were constructed, and control group, model group (AA), AA+BMSC group, AA+NC-BMSC group, AA+Cxcr4-BMSC group were set up. Except control group and model group, the other three groups of mice were injected 400 μl exosomes from different sources via the tail vein, after 2 weeks, the routine blood indices and the number of bone marrow nucleated cells were detected, the pathological changes of bone marrow were observed by HE staining, and the expression level of Treg cells was detected by flow cytometry. RESULTS: Mouse BMSCs were successfully isolated, and BMSCs with high expression of Cxcr4 and their exosomes were obtained. Compared with the control group, the number of red blood cell (RBC), white blood cell (WBC), and platelet (PLT), the hemoglobin (Hb) content and proportion of Treg cells in the peripheral blood of mice in the model group significantly decreased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). The proliferation level of nucleated cells was low, and the medullary cavity was filled with a large number of fat cells. Compared with the model group, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+BMSC group, AA+NC-BMSC group, and AA+Cxcr4-BMSC group significantly increased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01), and pathological changes of bone marrow were improved. In addition, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+Cxcr4-BMSC group were significantly higher than those in the AA+BMSC group (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). CONCLUSION Injection of Cxcr4 gene-modified BMSC-derived exosomes has a certain improvement effect on AA mice, and the mechanism may be related to an increase of the proportion of Treg cells.
Anemia, Aplastic/metabolism* ; Animals ; Bone Marrow Cells ; Exosomes/metabolism* ; Humans ; Mesenchymal Stem Cells ; Mice ; Receptors, CXCR4

Objective:To observe the effect of different doses of Fufang Huangbaiye Tuji asin the treatment onof the inflammatory response in healing process for of skin with deep Ⅱ degree burn. Methods in healing process. Methods:The 120 cses patients with deep Ⅱ degree burn of fire-toxin injuring fluid syndrome diagnosed in the affiliated hospital of Chengde Medical University between June 2019 and March 2020 were randomly divided into control group，low -dose treatment group and high -dose treatment group，with 40 cases in each group and once. They got a dressing change perevery day. Control group was locally administered with lodophor solution 35 mL per 1% on the body surface area. Low-dose treatment group was locally administered with compound cortex phellodendri fluid 17.5 mL per 1% on the body surface area，while high-dose treatment group was locally administered with compound cortex phellodendri fluid 35 mL per 1% on the body surface area. Observe theThe inflammatory reaction of wound surface in each group onwas observed at admission and after treatment. The pathological changes of each groupsgroup were observed， and determination of nuclear factor kappa-B（NF-κB） p65 expression inon the wound surface was determined by immunohistochemistry on the 4th day after the treatment. The levels of interleukin（IL）-2，IL-8 and tumor necrosis factor（TNF）-α in wound tissue were measured with ELISA and Bacterial culture and count were performed in each group on the 4^th，10^th and 21^st daydays after treatment. The levels of IL-2，IL-8 and TNF-α in wound tissue were measured with ELISA. Results:There was no significant difference in the degree of wound inflammation in each group at admission，and the degree of relief after treatment was positively correlated with the treatment time. At the simultaneous phase point，the inflammatory reaction was severest in control group，which was followed by low-dose treatment group and high-dose treatment group. Bacterial growth were observed on the 4^th day in control group，which was found in low-dose and high-dose treatment groups on the 10^th day，the detection rates of Staphylococcus aureus and Pseudomonas aeruginosa were the highest. Compared with control group，the mean integrated optical density of NF-κB p65 in wound tissue decreased markedly in low-dose and high-dose treatment groups on the 4th day after treatment（P<0.05），the bacterial count decreased significantly in low-dose and high-dose treatment groups on the 10^th and 21^st days after treatment（P<0.05），and the levels of IL-2，IL-8 and TNF-α in wound tissue decreased markedly in low-dose and high-dose treatment groups on the 4^th，10^th and 21^st days after treatment（P<0.05），with statistically significant differences between low-dose and high-dose treatment groups（P<0.05）. Histopathological examination showed that inflammatory granulocytes and edema were improved in low-dose and high-dose treatment groups compared with control group，with a more significant performance in high-dose treatment group. Conclusion:The external application of compound cortex phellodendri fluid can reduce thebacterial growth of bacteria in on the wound surface，which may reduce the inflammatory reaction by inhibiting the production and release of inflammatory mediators，with a certain dose-effcteffect relationship，and is worth clinical promotion.

Objective:To study the intervention effect and underlying mechanism of Fufang Huangbaiye Tuji （FFHBY） on skin with deep Ⅱ degree burn wound. Method:Patients with deep Ⅱ degree burn of fire-toxin injuring fluid syndrome diagnosed in the Affiliated Hospital of Chengde Medical University from June 2019 to June 2020 were randomly divided into a control group （iodophor solution， 35 mL per 1% body surface area）， a low-dose treatment group （FFHBY， 17.5 mL per 1% body surface area）， and a high-dose treatment group （FFHBY， 35 mL per 1% body surface area）， 40 cases in each group. The patients in each group were treated correspondingly with dressing chance once per day. The pathological changes of the wound were observed on the 14th day after treatment. Wound symptoms and signs in each group before treatment and on the 7th， 14th， and 21st days after treatment were quantified， and the clinical efficacy on the 21st day after treatment was evaluated. Wound healing rates in each group were calculated on the 7th， 14th， and 21st days after treatment. The levels of vascular endothelial growth factor （VEGF）， fibroblast growth factor （FGF）-2， FGF-7， epidermal growth factor （EGF）， interleukin （IL）-10， tumor necrosis factor （TNF）-α， and Caspase-3 in wound tissues were measured with enzyme-linked immunosorbent assay （ELISA）. Nuclear factor kappa-B （NF-κB） p65 expression in wound surface was detected by immunohistochemistry. The apoptosis rate in wound tissues was determined by the TdT-mediated dUTP-biotin nick end labeding assay （TUNEL） method. Result:There was no significant difference in scores of symptoms and signs among groups before treatment. Compared with the control group， the treatment groups showed no significant difference in wound healing rates on the 7th day after treatment and increased healing rates on the 14th and 21st day after treatment（P<0.05）. The clinical efficacy in the treatment groups was superior to that in the control group on the 21st day after treatment. Additionally， the treatment groups also showed decreased scores of local symptoms and signs， increased levels of VEGF， FGF-2， FGF-7， EGF， and IL-10， and dwindled apoptosis rate and levels of Caspase-3， TNF-α， and NF-κB p65 expression in wound tissues on the 7th，14th and 21st day after treatment （P<0.05）. The high-dose treatment group was superior to the low-dose treatment group in the above indicators （P<0.05）. Histopathological examination showed that inflammatory cell infiltration was relieved in the treatment groups as compared with that in the control group， and the high-dose treatment group exhibited superior efficacy. Conclusion:FFHBY had an obvious therapeutic effect on deep Ⅱ degree burn. It could promote wound healing by up-regulating the level of growth factors， improving inflammatory response， and inhibiting cell apoptosis in a dose-dependent manner.

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.