The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Znic (Zn) alloys with good cytocompatibility and suitable degradation rate have been a kind of biodegradable metal with great potential for clinical applications. This paper summarizes the biological role of degradable Zn alloy as bone implant materials, discusses the mechanical properties of different Zn alloys and their advantages and disadvantages as bone implant materials, and analyzes the influence of different processing strategies (such as alloying and additive manufacturing) on the mechanical properties of Zn alloys. This paper provides systematic design approaches for biodegradable Zn alloys as bone implant materials in terms of the material selection, product processing, structural topology optimization, and assesses their application prospects with a view to better serve the clinic.
Orthopedics ; Zinc ; Alloys ; Dental Materials ; Prostheses and Implants

Objective:To investigate clinical manifestations, pathological features and diagnosis of eczematoid clear cell acanthoma of the nipple/areola.Methods:The clinical manifestations, histopathological features, special staining results and immunohistochemical features of a case of eczemtoid clear cell acanthoma of the nipple/areola firstly reported in China were analyzed, and compared with those of similar cases in foreign literature.Results:The female patient presented with recurrent pruritic rashes on the left nipple and areola for over 2 years. Skin examination showed hypertrophic skin on the left nipple and areola, and scattered erythema, hypopigmented macules and hyperpigmented macules on the areola, which were covered with a few crusts and scales. Histopathological examination of the skin lesions showed focal epidermal crusts and scales, focal parakeratosis, extended and fused rete ridges, thickened spinous layer, focal spongiosis, clear cell clumps in the spinous cell layer, telangiectasia in the superficial dermis, with infiltration of a few eosinophils and neutrophils. Periodic acid-Schiff staining showed positive results, and immunohistochemical staining revealed positive reaction for epithelial membrane antigen. Topical treatment with triamcinolone acetonide and econazole cream was effective, and topical application of 3% boric acid solution could alleviate exudation. During the 6-month follow-up, the patient experienced intermittent recurrence twice, and responded well to the above treatment.Conclusions:Eczematoid clear cell acanthoma of the nipple/areola has unique clinical and pathological features, revealing that it′s a new subtype of clear cell acanthoma. Pathological examination is the gold standard for its diagnosis.

Objective:To investigate the association between serum sex hormone-binding globulin (SHBG) and non-alcoholic steatohepatitis (NASH).Methods:In this cross-sectional study, a total of 371 middle-aged and young obese patients who were hospitalized and underwent liver puncture in Nanjing Drum Tower Hospital from January 2016 to April 2021 were included. The population was divided into control group ( n=43) and non-alcoholic fatty liver disease (NAFLD) group ( n=328) based on the non-alcoholic fatty liver disease activity score. Subjects in NAFLD group were further divided into non-alcoholic fatty liver (NAFL) ( n=60), uncertain-NASH ( n=172), and NASH ( n=96). Serum SHBG was tested in patients with NAFLD who were divided into three subgroups according to tertiles. The liver pathological characteristics in different SHBG level subgroups were compared. The risk factors of NASH were analyzed by logistic regression. The prediction model of NASH noninvasive diagnosis was established by forward stepwise regression, and the diagnostic value of non-invasive model for NASH was evaluated by receiver operating characteristic (ROC) curve. Results:The median age in patients were (32±10) years old with a body mass index of (39.16±6.58) kg/m2, including 236 females (63.6%). Serum SHBG level [ M ( Q1, Q3)] in NAFLD group was significantly lower than that in control group [16.90 (11.43, 23.00) vs. (23.45 (15.40, 31.22) mmol/L, P<0.05], and progressively diminished in NAFL, uncertain-NASH and NASH subgroups [(22.24±10.47), (20.57±19.58), (15.80±8.74) mmol; P for trend<0.05]. Compared with the high-leveled SHBG subgroup, the steatosis score (2.09±0.80 vs. 1.51±0.72, P<0.01) and lobular inflammation score (1.10±0.68 vs. 0.85±0.68, P<0.05) were significantly higher in the low-leveled SHBG group. Multivariate logistic regression analysis indicated that lower serum SHBG level was an independent risk factor for NASH ( OR=2.527, 95% CI: 1.296 to 4.928, P<0.05). The area under ROC curve of SHBG combined with aspartate aminotransferase in predicting NASH in NAFLD patients was 0.752 (95% CI: 0.696 to 0.809). Conclusion:Low serum SHBG level is associated with NASH.

Objective:To analyze parents' knowledge, attitudes and practice (KAP) on antibiotics use in children.Methods:A survey of parents' KAP on antibiotics use in children was conducted among 482 parents in Tangqiao community who were visiting the vaccination unit of our center during January to June 2018. The influencing factors of patients' KAP on antibiotics use in children were investigated with univariater and multivariate logistic regression analysis.Results:In terms of knowledge, 89.0% (429/482) of parents agreed that common cold did not require antibiotics treatment; 88.8% (428/482) of parents knew that antibiotics had adverse reactions; 82.0% (395/482) of parents knew that overuse of antibiotics would increase the possibility of drug resistance of pathogenic bacteria; and 69.7% (327/482) of the relevant knowledge acquisition came from doctors. In terms of attitudes, 84.1% (405/482) of the parents agreed with the phenomenon of excessive use of antibiotics in our country; 68.2% (405/482) of the parents agreed that they should follow the doctor's instruction but not ask the doctor to prescribe drugs; 30.7% (148/482) parents thought they had enough knowledge about antibiotics drugs; 24.7% (148/482) parents were willing to use more expensive antibiotics for their children. In terms of practice, 13.9% (67/482) of parents would buy antibiotics by themselves; 35.7% (172/482) of parents had antibiotics at home. Multi-factor regression analysis results showed that parents with high annual family income are likely to better understand antibiotics ( OR=2.619, 95 %CI: 1.431—4.793); parents who had antibiotics at home ( OR=4.713, 95 %CI: 1.964—11.309)and purchased antibiotics by themselves ( OR=2.768, 95 %CI: 1.237—6.194) were more likely to use antibiotics for their children. Conclusion:There are still some problems in parents' knowledge, attitude and behavior of using antibiotics in children in the community, and public education on rational use of antibiotics in children is necessary.

Objective To investigate the correlation between serum vitamin D level in human body and Chlamydia trachomatis (Ct) genitourinary tract infection. Methods This study enrolled 174 outpa-tients (male: 95, female: 79, 20-49 years) infected with Ct and 380 healthy subjects (male: 211, female:169, 20-49 years) in Tianjin from November 1, 2016 to March 15, 2017. Blood samples were collected from all subjects after fasting overnight and the time points for sample collection in the Ct infection group were before and after a course of antibiotic treatment. Serum 25-hydroxyvitamin D [25-(OH)D] levels were measured with enzyme-linked immunosorbent assay (ELISA). PCR assay was used to assess the recovery in those patients one month after a course of treatment. Two case-control studies were respectively conducted, in which 161 patients and 161 healthy subjects as well as 41 uncured patients and 41 cured patients were randomly selected and matched for gender and age. Statistical analysis was performed using SPSS19. 0. Re-sults The two case-control studies showed that vitamin D deficiency was a risk factor for both Ct genital tract infection and poor efficacy, of which the adjusted ORs were 2. 281 (95％ CI: 1. 438, 3. 619) and 7. 266 (95％ CI: 2. 551, 21. 036). Among all subjects aged 20-39, male patients had lower 25-(OH)D level in serum than healthy men [(40. 10±17. 93) nmol/ L vs (53. 72±18. 00) nmol/ L, P< 0. 01] and fe-male patients also had lower 25-(OH)D level in serum than healthy women [(35. 71±19. 99) nmol/ L vs (45. 42±16. 08) nmol/ L, P<0. 01]. The levels of 25-(OH)D in uncured male and female patients were re-spectively lower than those in cured male and female patients [(30. 50±14. 53) nmol/ L vs (41. 32±17. 24) nmol/ L; (29. 47±16. 66) nmol/ L vs (41. 37±21. 03) nmol/ L; both P<0. 05]. Conclusion Vitamin D deficiency related to Ct infection in human genitourinary tract and poor prognosis. Lower serum vitamin D levels might increase the risk of Ct genitourinary tract infection and reduce the efficacy of treatment.

Objective To explore the feasibility and application in quantifying the rabbit central nervous system by using magnetic resonance diffusion tensor imaging(DTI)sequences.Methods 12 normal New Zealand rabbits were used to scan the brain and spinal cord of rabbits by DTI sequence of 1.5T MR machine,and the normal apparent diffusion coefficient(ADC)and fractional anisotropy (FA)values were obtained in the different regions of the brain and every spinal segment of rabbits,to analyse the characteristics and regularity of numerical changes.Results The average ADC value in the brain of rabbits was (0.87±0.08)×10-3mm2/s,the average FA value was 0.23±0.09;the average ADC value in cervical spinal cord was (1.05±0.14)×10-3mm2/s,the average FA value was 0.55±0.08.The average ADC value in thoracic spinal cord was (1.14±0.12)×10-3mm2/s,and the average FA value was 0.57±0.06;the average ADC value in lumber spinal cord was (1.20±0.12)×10-3mm2/s,and the average FA value was 0.61±0.06.Conclusion FA average value in the brain is lower than that in spinal cord (P<0.001),the difference is related to the distribution of nerve fibers and physiological curvature of spine.ADC average value in the brain is lower than that in spinal cord(P<0.001),this is related to the volume of spinal canal and the peripheral structure of spinal cord.The difference of FA value in the brain and spinal cord is higher than ADC value.

Background Peters anomaly is a rare eye disease.Understanding the clinical features of Peters anomaly is helpful for us to correctly manage this disease.Objective This study was to investigate the clinical characteristics and treatment methods of Peters anomaly and provide available basis for the diagnosis and individualized treatment of Peters abnormal.Methods A descriptive study was performed.The clinical data from 8 eyes of 4 patients with Peters anomaly who were diagnosed and treated in Beijing Children's Hospital from January 1,2014 to March 30,2016 were retrospectively analyzed.The clinical manifestations of the anterior ocular segment were examined by handheld slit-lamp microscope,and corneal curvature,corneal thickness,axial length and intraocular pressure were measured.The therapy and outcomes of the patients were evaluated.Results Peters anomaly was classified into type Ⅰ,type Ⅱ and Peters plus syndrome based on the findings and literature'criteria.Regarding to the clinical findings,the adhesion of peripheral angle with cornea,shallow or disappeared anterior chamber were found in all the eyes,and these manifestations were type Ⅰ Peters anomaly and occurred in 2 eyes of 2 patients.The opacity and adhesion of the central lens capsula to corneal endothelium was seen in 6 eyes which belonged to type Ⅱ Peters anomaly.The mean corneal thickness was (680± 127) μm in 4 measured eyes,which was thicker than normal eyes;the mean corneal curvature was (37.40±1.79)D in 4 measured eyes;the mean axial length was (21.06±0.19)mm and the mean diameter of cornea was (9.4 ± 0.5) mm in 4 measured eyes.Iridocoloboma was found in 4 eyes and congenital aniridia was in 4 eyes.In addition,esotropia appeared in 1 patient,and nystagmus occurred in 3 patients.The 3 patients of type Ⅱ in this study were found to have the disorders associated with systemic neurogenic developmental abnormalities and diagnosed as Peters plus syndrome.Trabeculectomy with anterior vitrectomy was performed in 2 eyes with the intraocular pressure ＞30 mmHg(1 mmHg =0.133k Pa) and the introcular pressure reduced to below 21 mmHg after operation.Penetrating corneal transplantation was carried out on 1 eye with central opacity.However,rejection of graft occurred at 1 month and became complete cloudy at 3 months after surgery.Cataract extraction surgery was performed on 4 eyes with lens opacity and intraocular lens were implanted in 2 eyes or iridectomy was carried out in another 2 eyes,and the visual quality was evidently improved after operation.Conclusions The clinical characteristics of Peters anomaly include leukoma,shallow anterior chamber,peripheral iris adhesion with cornea and lens opacity due to adhesion of lens anterior capsule to corneal endothelium.Personalized operative regimen should be determined based on the clinical findings of the eyes with Peters anomaly.

[Objective]To investigate the expression change of miR-134 in methamphetamine(MA)-induced neuronal injury in PC12 cells and its effect on neuronal excitability and understand the pathogenesis of methamphetamine-induced neuronal injury.[Methods]PC12 cells in the logarithmic phase were divided into control group and MA group. The MA group was treated with 800μmol/L MA to establish the model of neuronal injury. The cellular injury was observed under microscope. The neuronal apoptosis was detected by Hoechst3342/PI double staining,and miR-134 expression was measured by using real-time quantitative PCR (Real time-PCR). Furthermore,we constructed miR-134 interference vector and observed its effect on evoked action potential.[Results]The cultured PC12 cells were damaged under the 800 μmol/LMA treatment ,and neurites became shorter ,the apoptotic cells were evidence. Real time-PCR showed that miR-134 expression was increased after MA treatment. Electrophysiological data showed that the evoked action potential increased after miR-134 interference.[Conclusions]High concentration of MA can induce neuronal damage and apoptosis and also increase miR-134 expression. While silence miR-134 expression can increase neuronal excitability.Our study provides an experimental basis for elucidating the possible mechanism of MA-induced neuronal injury and the role of miR-134 in neurotoxicity and neuronal excitability.

Objective To assess the clinical and radiologic outcomes between laminoplasty with forominotomy(LF) and anterior cervical discectomy and fusion(ACDF) in treating cervical radiculomyelopathy(CRM). Methods Datas of 68 patients (ACDF=33, LF=35) from January 2008 to January 2010 was collected retrospectively, the follow-up is at least 2 years. The Japa-nese Orthopedic Association (JOA) score and associated recovery rate were evaluated. For radiographic evaluation, the lordotic an-gle and range of motion (ROM) at C2-C7 were investigated. The Neck Disabilitv Index Scale(NDI) was used to evaluate the degree of patient’pain at the last follow-up. Results Patients’demographics were similar between the two groups. The differences be-tween ACDF and LF in operative time (187min VS 154min),the blood loss (127 ml VS 235 ml) and the sensation of lower extremity (64.0%VS 66.0%) are significant(t=4.170, P=0.000;Z=-6.888, P=0.000;Z=-7.512, P=0.000). 1 case with failed fusion of bone graft 3 months post-operation. 3 cases of adjacent segment degenerative changes occurred at the 2nd year follow-up in ACDF group. But no such complications occurred in the EOLF group. In addition, ACDF group showed lower NDI score than LF group in extracting and amusing (Z=-3.947, P=0.000;t=-7. 523, P=0.000). Cervical lordosis of ACDF increased from 13.7° to 16.2°, while that of LF group decreased from 14.6° to 13.3°(Z=-3.374,P=0.001);Both of the two groups (ACDF/LF) exhibited decreased cervi-cal ROM (14.8° VS 16.5°, t=-2.167, P=0.034). Conclusion The two surgical procedures have similar clinical effects in treating multi-segmental CRM. However, the LF group demonstrated shorter operative time, fewer short-term complications, so it proved to be effective and safe surgical procedure.