To investigate the association between obesity-related metabolic indices and the risk of knee osteoarthritis(KOA) in middle-aged and older Chinese adults(≥45 years) using data from the China Health and Retirement Longitudinal Study(CHARLS).

Objective To compare the application value of three image post-processing techniques volume rendering(VR),multiplanar reformation(MPR)and curved planar reformation(CPR)in the identifi-cation of rib fracture malunion.Methods The types and numbers of rib fracture malunion in 75 pa-tients were recorded,and the sensitivity,specificity,accuracy and Youden index of VR,MPR and CPR in the diagnosis of rib fracture malunion were compared.Receiver operator characteristic(ROC)curve was drawn and area under the curve(AUC)was calculated,and the detection rates of three image post-processing techniques for different types of rib fracture malunion were compared.Results A total of 243 rib fractures were malunion in 75 patients.The diagnostic sensitivity of VR,MPR and CPR for rib fracture malunion was 52.67%,79.84%and 91.36%,the specificity was 99.58%,97.89%and 99.15%,the accuracy was 83.66%,91.76%and 96.51%,the Youden index was 0.52,0.78 and 0.91,the AUC was 0.761,0.889 and 0.953,respectively.Compared with VR,there were statistically signifi-cant differences in the number of broken rib end misalignment over 1/3,broken rib end overlap,bro-ken rib end angulation and intercostal bridge detected in MPR(P<0.05).Compared with VR,there was a statistically significant difference in the number of different types of rib fracture malunion de-tected by CPR(P<0.05).Compared with MPR,there were statistically significant differences in the number of broken rib end misalignment over 1/3,broken rib end separation and intercostal bridge de-tected in CPR(P<0.05).Conclusion The three image post-processing techniques are of great signifi-cance for the identification of rib fracture malunion.Especially CPR is highly effective in the diagno-sis of rib fracture malunion,and can be used as the main post-processing technique for forensic clini-cal identification of rib fracture malunion.

Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Death, Sudden/etiology*

OBJECTIVE: The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker. METHODS: A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL). RESULTS: The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m ³. The OELs for COEs exposure using the BBMD were 0.00170 mg/m ³ for the total population, 0.00158 mg/m ³ for males, and 0.00174 mg/m ³ for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m ³, respectively. CONCLUSION Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m ³. This value will provide a benchmark for determining possible OELs.
Male ; Female ; Animals ; Coke ; Polycyclic Aromatic Hydrocarbons ; DNA Copy Number Variations ; Benchmarking ; Occupational Exposure/analysis* ; DNA, Mitochondrial/genetics* ; DNA Damage

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ²=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ²=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ²=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.
Male ; Female ; Child ; Humans ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Retrospective Studies ; Survival Analysis ; Mutation ; Hematopoietic Stem Cell Transplantation

:Aim To study the effects of continuous dai¬ly administration of ramelteon starting at the subacute period of cryogenic traumatic brain injury (cTBI) on neurological function and brain tissue repair in mice. Methods Thirty male C57BL/6 mice were randomly divided into sham group, vehicle group and ramelteon treatment groups. The right sensory-motor cortex was damaged by pressing a copper probe precooled by liq¬uid nitrogen onto the skull. Ramelteon ( 10 nig 'kg-1 • d"1) was administered by gavage every day starting at different time points after cTBI (1 h, 1 d,3 d) until sacrifice on day 14. Beam walking test and open field test were used to evaluate the motor function. Toluidine blue staining was used to measure the infarct volume. Immunofluorescence was used to detect the expression of GAP-43 and synaptophysin in peri-infarct area. Mi¬croglia activation was detected using Iba-1. The area and thickness of glial scars were analyzed by detecting GFAP positive areas. Results All three treatment ( 1 h - 14 d, 1 - 14 d, and 3 - 14 d) significantly im¬proved cTBI induced motor dysfunction, reduced the infarct volume, elevated the expression of GAP -43 and synaptophysin, and decreased the area and thick¬ness of glial scar and microglia activation. In addition, all ramelteon treatment groups had similar effects on the above indexes. Conclusions Delayed ramelteon treatment can improve neurological dysfunction after cTBI,and the therapeutic time window can be delayed for up to three days after cTBI. Inhibiting glial scar formation and microglia activation, and promoting ax- onal regeneration and synaptogenesis may contribute to the beneficial effects of ramelteon.

OBJECTIVE To investigate the mechanism of Xiaoai Jiedu Recipe in promoting ferroptosis of tumor cells and inhibi-ting the growth of transplanted tumors in hepatocellular carcinoma mice by proteomics method.METHODS C57BL/6J mice were randomly divided into,model group,low-and high-dose groups of Xiaoai Jiedu Recipe,Xiaoai Jiedu Recipe combined with ferropto-sis inhibitor group,ferroptosis inhibitor group and cisplatin group.The H22 mouse transplantation tumor model was constructed and the drug administration interventions were as follows:the low-and high-dose groups of Xiaoai Jiedu Recipe were given Xiaoai Jiedu Reci-pe by gavage at the doses of 10 and 20 g·kg-1·d-1;the ferroptosis inhibitor group was given Liproxstatin-1 by intraperitoneal injec-tion at the dose of 10 mg·kg-1·d-1;the cisplatin group was given cisplatin by intraperitoneal injection at the dose of 10 mg·kg-1·d-1;the Xiaoai Jiedu Recipe combined with ferroptosis inhibitor group was given a gavage dose of 20 g·kg-1·d-1of Xiaoai Jiedu Recipe and an intraperitoneal injection of 10 mg·kg-1·d-1 of the ferroptosis inhibitor Liproxstatin-1;the model group was given an equal amount of saline by gavage.The drugs were administered for 11 d continuously.The tumors were stripped to calcu-late tumor inhibition rate.Pathological changes were observed by hematoxylin-eosin(HE).Mitochondrial structural changes were ob-served by transmission electron microscopy.Reactive oxygen species(ROS)levels were detected by flow cytometry.Serum was pre-pared and analysed by TMT peptide labelling combined with LC-MS/MS to find differential protein expression profiles,applying IPA software.Serum iron ions,glutathione(GSH)and malondialdehyde(MDA)levels were measured biochemically.Protein expression levels of nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HMOX1),cystine/glutamate reverse transporter protein(SLC7A11)and glutathione peroxidase 4(GPX4)were measured by protein Western blot.RESULTS The tumor growth was inhibi-ted in the low-and high-dose groups and the cisplatin group,with inhibition rates of 36.12%,51.63%and 57.43%,respectively,while the tumor growth was promoted in the ferroptosis inhibitor group,with an inhibition rate of-45.56%,and the tumor size was re-duced in the Xiaoai Jiedu Recipe combined with ferroptosis inhibitor group compared with the ferroptosis inhibitor group,with an inhi-bition rate of 18.11%.HE staining showed that apoptotic cells and a large number of vacuoles accumulated in the tumor tissues of the high-dose group and the cisplatin group.Transmission electron microscopy showed that the mitochondrial atrophy and membrane densi-ty increased to a certain extent in the low and high-dose groups of Xiaoai Jiedu Recipe.Flow cytometry results showed that ROS levels were significantly increased after the intervention of Xiaoai Jiedu Recipe(P<0.01).Proteomic tests showed that there were 129 differ-ential proteins,including 62 down-regulated proteins and 67 up-regulated proteins,in the high-dose group of Xiaoai Jiedu Recipe compared with the model group,and these differential expressions were involved in lipid metabolism,et al.The results of biochemical tests showed that the intervention of Xiaoai Jiedu Recipe increased the serum iron and MDA levels,and decreased the GSH level in mice.Western blot results showed that the protein expression levels of Nrf2 and HMOX1 increased,and those of SLC7A11 and GPX4 decreased after the intervention of the high-dose group of Xiaoai Jiedu Recipe(P<0.01).CONCLUSION Xiaoai Jiedu Recipe pro-motes ferroptosis in hepatocellular carcinoma cells by inducing the Nrf2/HMOX1 signaling pathway,regulating oxidative stress and ele-vating the level of lipid peroxidation,which may be one of its mechanisms of action in inhibiting the growth of transplanted tumors.

On October 26,2022,Hunan Armed Police Corps Hospital admitted a 25-year-old male patient with＂ hepatic sparganosis＂.The patient was admitted to the hospital for＂ persistent pain in the upper abdomen for 1 day＂,and described having swallowed river water while swimming a month prior.Physical examination revealed tenderness and rebound pain in the right lower abdomen,and percussion pain in the liver area.A full-panel antibody test for parasites revealed positivity for schizocephala-specific IgG.Combined imaging results,serum laboratory examination and exposure history,a diagnosis of ＂hepatic sparganosis＂ was supported.Twenty days after anti-infection and whole-body deworming treatment,liver lesions observed by abdominal enhanced CT were significantly reduced,routine blood panel was recovery,and the patient's symptoms completely disappeared.

Objective To evaluate the molluscicidal effect of 50% wettable powder of niclosamide ethanolamine salt (WPNES) against Oncomelania hupensis on the soil surface and inside the soil layer by immersion method in winter. Methods O. hupensis snails were placed on the soil surface and 2, 5 cm and 10 cm under the soil layer outdoors in winter, and then immersed in 50% WPNES at concentrations of 1 mg/L and 2 mg/L for 1, 3 d and 7 d, while dechlorinated water served as controls. Snail mortality was observed following immersion with 50% WPNES on the soil surface and inside the soil layer. Results Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 3-day corrected snail mortality rates were 98.0% and 76.0% on the soil surface, and the 7-day corrected snail mortality rate was both 100.0%. Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 7-day corrected snail mortality rates were 95.5% and 85.6% 2 cm below the soil layer, 66.0% and 6.4% 5 cm below the soil layer. However, the 7-day snail mortality rate swere comparable between the 50% WPNES treatment group (at 2 mg/L and 1 mg/L) and controls 10 cm below the soil layer (both P > 0.05). Conclusion Immersion of 50% WPNES at a concentration of 2 mg/L for 7 days presents a high molluscicidal efficacy against O. hupensis on the soil surface and 5 cm within the soil layers in winter.