The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Objective To investigate the value of histone deacetylase 3(HDAC3)in evaluating the risk of slow/no reflow in AMI patients after PCI.Methods A total of 280 AMI patients undergo-ing PCI in our hospital from June 2020 to June 2022 were recruited,and according to TIMI blood flow grading,they were divided into slow/no reflow group(TIMI≤grade 11,n=54)and normal flow group(TIMI＞grade Ⅱ,n=226).The demographic characteristics,underlying diseases,baseline data at admission,and preoperative results of coronary angiography and laboratory tests were compared between the two groups.Multivariate logistic regression analysis was used to determine the influencing factors for slow/no reflow in AMI patients after PCI,and ROC curve was drawn to analyze the predictive value of related indicators for slow/no reflow.Results Obvi-ously larger proportions of smoking history and Killip grade Ⅱ,higher heart rate,longer reperfu-sion time,and higher serum levels of LDL-C,NLR,D-D and HDAC3 were observed in the slow/no reflow group than the normal flow group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that reperfusion time,NLR and HDAC3 were influencing factors for slow/no reflow in AMI patients after PCI(P＜0.05,P＜0.01).The AUC value of reperfusion time+NLR in predicting the slow/no reflow after PCI in AMI patients was 0.798(95％CI:0.664-0.922,P=0.002),with a sensitivity and specificity of 0.87 and 0.73,respectively.And when serum HDAC3 level was combined in the prediction,the AUC value was 0.903(95％CI:0.790-0.922,P＜0.01),with a sensitivity and specificity of 0.93 and 0.84,respectively.Conclusion Preoperative HDAC3 level is an influencing factor for slow/no reflow in AMI patients after PCI.Based on reperfusion time and NLR,combination of the 3 indicators can provide additional predictive value for slow/no reflow in these patients.

[Objective] To analyze the characteristics of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 allele polymorphisms among cord blood donors in Guangdong population. [Methods] According to HLA high resolution genotyping data of 32 717 samples of cord blood donors from Guangdong Cord Blood Bank from January 2009 to December 2023, the allele frequencies were calculated by direct counting and the haplotype frequencies were calculated by using Arlequin software 3.5.2.2. [Results] A total of 102 HLA-A alleles, 160 HLA-B alleles and 96 HLA-DRB1 alleles were detected in 32 717 samples. Among them, 46 HLA-DPB1 alleles were detected in 5 377 samples, and 66 HLA-C alleles and 35 HLA-DQB1 alleles were detected in 13 310 samples. The most common alleles were HLA-A^*11∶01 (28.96%), HLA-B^*40∶01 (15.23%), HLA-DRB1^*09∶01 (15.72%), HLA-C^*01∶02 (19.40%), HLA-DQB1^*03∶01 (20.85%) and HLA-DPB1^*05∶01 (40.79%). The most common 3 loci haplotype and 6 loci haplotype were HLA-A^*02∶07-B^*46∶01-DRB1^*09∶01 (1.55%), HLA-C^*07∶02-DQB1^*03∶01-DPB1^*05∶01 (1.77%), HLA-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (3.31%) and HLA-A^*02∶07-B^*46∶01-C^*01∶02-DRB1^*09∶01-DQB1^*03∶03-DPB1^*05∶01 (0.30%). [Conclusion] In this study, the allele and haplotype frequencies of HLA-A, HLA-B, HLA-DRB1, HLA-C, HLA-DQB1 and HLA-DPB1 were obtained in the cord blood donors in Guangdong, which can provide important reference data for HLA gene related research and the selection of donors for clinical application.

Objective:To explore the mid-term efficacy of liquid nitrogen-inactivated autologous tumor segment bone replantation for repairing bone defects after resection of malignant tumors in the long bone shaft.Methods:A retrospective analysis was performed on the clinical data of 16 patients treated with liquid nitrogen-inactivated autologous bone graft at Beijing Jishuitan Hospital from July 2015 to June 2017 to repair defects caused by malignant tumour resection of the diaphysis. There were 10 males and 6 females with a mean age of 23.4±11.6 years (range, 8-44 years), including 8 classic osteosarcoma, 2 high-grade surface osteosarcoma, 4 Ewing's sarcoma, 1 periosteal osteosarcoma, and 1 undifferentiated pleomorphic sarcoma. Tumors were located in the humerus in 2 cases, in the femur in 8 cases and in the tibia in 6 cases. The mean length of tumor was 12.4±4.8 cm (range, 5.5-26 cm). Postoperative imaging examination was performed every 6 months, and the healing status of the transplanted bone-host bone was evaluated based on the imaging assessment method of the International Society of Limb Salvage (ISOLS) imaging assessment after allogeneic bone transplantation, and the complications were assessed using the Henderson classification. The five-year survival rate for patients and grafted bone was calculated using the Kaplan-Meier survival curve.Results:The median follow-up was 64 (60.3, 69.8) months. At the end of follow-up, 13 patients were tumour free and 3 patients died of multiple metastases at 19, 20 and 33 months after surgery. There were 32 osteotomy ends in 16 patients, of which 30 healed, including 11 metaphyseal osteotomy ends, and the healing time was 9 (6, 12) months after replantation of the tumour segment with liquid nitrogen-inactivated autologous bone; 19 osteotomy ends in the diaphysis took 13 (9, 21) months to heal, with a statistically significant difference in healing time between different sites ( Z=-2.25, P=0.025). Sixteen patients had six complications, including two cases of non-union at the diaphyseal site, one case of failure of internal fixation due to non-union, three cases of recurrence, and no soft tissue complications or infections. One patient with failed internal fixation was treated with a vascularized tip iliac bone graft that healed 6 months after surgery. Another patient died of multiple metastases with 1 unhealed diaphysis left. Three cases of recurrence were all located in the extracranial soft tissue of the autologous tumor segment inactivated by liquid nitrogen. Among them, one case underwent reoperation and local radiotherapy, and there was still no tumor survival after 65 months of surgery, and two cases died due to multiple metastases. The five-year survival rate of patients was 81% as calculated using the Kaplan-Meier survival curve, and the graft survival rate was 100%. There was no amputation and the limb salvage rate was 100%. Conclusion:The use of liquid nitrogen-inactivated autologous tumor segment bone replantation for reconstruction of bone defects after resection of malignant tumors in the shaft has advantages of higher healing rate, shorter healing time at the metaphyseal end compared to the osteotomy end, fewer complications, and higher survival rate of the replanted bone.

Objective To describe the epidemiological and clinical characteristics of fibrous dysplasia of bone admitted to a single center in the past 30 years. Methods We analyzed the clinical features of 744 patients with bone fibrous dysplasia diagnosed by pathology, including age, gender, disease location, monostotic or polyostotic lesions, pathological fracture and malignant transformation. Results There were 1183 lesions in 744 patients. The mean age at admission was 31.1±13.5 years old. The ratio of male to female was close to 1:1. The most common site was the lower extremities (916(77.4%)), followed by the upper extremities (106(9.0%)). The most common sites of lower extremities were the femur (645(54.5%)) and the tibia (224(18.9%)). Polyostotic cases accounted for 25.4%, and monostotic cases accounted for 74.6%. Pathological fracture occurred in 163 (13.8%) patients. There were 6 (0.8%) patients with malignant transformation. The mean age was 40.5 years old. The mean time of malignant transformation was 7.7 years. Conclusion Fibrous dysplasia of bone is a rare group of benign bone tumors, with typical epidemiological and clinical features.

Objective To determine the prosthesis survival and limb function after revision of global modular replacement system (GMRS) tumor prosthesis. Methods We retrospectively analyzed the clinical data of 16 patients who developed aseptic loosening of lower extremity tumor prosthesis and subsequently received revision with GMRS from 2009 to 2012. Kaplan-Meier method was used to calculate the 5- and 8-year survival rates of the prosthesis. The MSTS function scale was used to evaluate the functional outcomes. Results The average follow-up time was 90 months (52-118 months). The 5- and 8-year survival rates of GMRS prosthesis were both 94%. After revision, two patients failed, including one case of infection and one case of repeated aseptic loosening. The average interval between the first joint replacement and revision surgery was 81 months (27-187 months). Until the last follow-up, 93.3%(14/15) of the patients did not develop repeated aseptic loosening, 85.7%(12/14) of the patients who underwent GMRS revision had a longer loosening-free survival than those with the primary joint replacement (90.6±19.3 vs. 43.4±29.7 months, P=0.001). The average MSTS functional score was 27.7(24-30). Conclusion The incidence of repeated aseptic loosening for GMRS prosthesis is low and the limb function is good. The reported technique is satisfactory in the middle and long term.

OBJECTIVE：To compare the chemical constituents of petroleum ether fraction from ethanol extract of Aconitum sinomontanum before and after processing. METHODS ：After A. sinomontanum was purified with water ，the raw product decoction pieces were prepared ；the raw decoction pieces were steamed with licorice juice under high pressure to prepare processed decoction pieces of A. sinomontanum . The petroleum ether fractions of raw product and processed product were obtained after ultrasonic extraction with 95％ ethanol. The chemical constituents in the samples were analyzed by GC-MS. NIST 2014 mass spectrometry database was used to compare and match the components . The peak area normalization method was used to determine the relative percentage content of each component. RESULTS ：Before and after processing ，fatty acids and esters were the main components in the petroleum ether fraction from ethanol extract. Totally 18 chromatographic peaks were detected in the detection pieces of raw product，and 13 compounds were identified ，accounting for 94.60％ of the total content of volatile components. The components with relatively high content were （Z，Z，Z）-9，12，15-octadecatrienoic acid （26.13％），hexadecanoic acid ethyl ester （25.27％）， palmitoleic acid （10.84％），ethyl linoleic acid （10.67％），（Z，Z）-9，12-octadecenoic acid methyl ester （6.66％），pentadecanoic acid（5.11％）and so on. Totally 25 chromatographic peaks were detected in the decoction pieces of processed products，and 18 components were identified ，accounting for 82.40％ of the total content of volatile components. The components with relatively high content were palmitoleic acid （18.95％），（Z，Z）-9，12-octadecenoic acid methyl ester （17.93％），hexadecanoic acid ethyl ester（11.94％），（Z，Z，Z）-9，12，15-octadecatrienoic acid （10.54％），（Z，Z）-9，12-octadecenoic acid （5.51％），（Z）-11-hexadecanoic acid（5.30％）and so on. After processing ，7 new components were added ，5 of which were identified as （－）-eucalyptus globulus alcohol，ethyl 2-methyltetrade-canoate，6-methyl-4-phenylcoumarin，β-sitosterol，heptadecane. After processing ，no components disappeared，and the content of some components increased or decreased. CONCLUSIONS ：After processing ，the volatile components in the petroleum ether fraction from ethanol extract of A. sinomontanum are different ，and（－）-eucalyptus globulus alcohol and other components are added after processing.

Object:This study aims to compare the efficacy, acceptability and tolerability of cognitive behavior therapy (CBT), pharmacotherapy, and their combination therapy for acute panic disorder via network Meta-analysis.Methods:Electronic databases including PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for relevant randomized controlled clinical trials from their inception up to March 24, 2021. The outcomes were efficacy (remission rate and response rate), acceptability and tolerability. Network Meta-analysis was adopted with random effects, and estimated relative risk (RR) for all effects of CBT, CBT plus medications, selective serotonin-reuptake inhibitors(SSRIs), serotonin-noradrenaline-reuptake inhibitors(SNRIs), tricyclic antidepressants(TCAs), monoamine oxidase inhibitors(MAOI), benzodiazepines(BZD), noradrenergic-reuptake inhibitors(NRI), and others. This study used gemtc package in R for network analysis, Review Manager for quality assessment, and GRADEPro for evidence assessment, respectively.Results:Identified citations (7 173) included 72 trials comprising 12 293 patients. The treatment measures with higher remission rate and response rate than placebo included CBT+drug( RR:2.4, 95% CI: 1.7-3.5), CBT( RR:1.8, 95% CI:1.4-2.3), SNRI( RR:1.8, 95% CI:1.5-2.2), BZD( RR:1.6, 95% CI:1.4-1.9), SSRI( RR:1.5, 95% CI:1.4-1.7), TCA( RR:1.5, 95% CI: 1.4-1.8)(remission rate in brackets); Among them, CBT combined with medications was better than SSRI, SNRI and TCA. The acceptability of BZD was better than placebo but its tolerability was inferior. Besides, the tolerability of SSRI and TCA was inferior to placebo. Conclusions:CBT combined with medications is more effective than BZD alone and the antidepressants alone. CBT combined with medications may selected the first-line treatment for panic disorder.

Object:This study aims to compare the efficacy, acceptability and tolerability of cognitive behavior therapy (CBT), pharmacotherapy, and their combination therapy for acute panic disorder via network Meta-analysis.Methods:Electronic databases including PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for relevant randomized controlled clinical trials from their inception up to March 24, 2021. The outcomes were efficacy (remission rate and response rate), acceptability and tolerability. Network Meta-analysis was adopted with random effects, and estimated relative risk (RR) for all effects of CBT, CBT plus medications, selective serotonin-reuptake inhibitors(SSRIs), serotonin-noradrenaline-reuptake inhibitors(SNRIs), tricyclic antidepressants(TCAs), monoamine oxidase inhibitors(MAOI), benzodiazepines(BZD), noradrenergic-reuptake inhibitors(NRI), and others. This study used gemtc package in R for network analysis, Review Manager for quality assessment, and GRADEPro for evidence assessment, respectively.Results:Identified citations (7 173) included 72 trials comprising 12 293 patients. The treatment measures with higher remission rate and response rate than placebo included CBT+drug( RR:2.4, 95% CI: 1.7-3.5), CBT( RR:1.8, 95% CI:1.4-2.3), SNRI( RR:1.8, 95% CI:1.5-2.2), BZD( RR:1.6, 95% CI:1.4-1.9), SSRI( RR:1.5, 95% CI:1.4-1.7), TCA( RR:1.5, 95% CI: 1.4-1.8)(remission rate in brackets); Among them, CBT combined with medications was better than SSRI, SNRI and TCA. The acceptability of BZD was better than placebo but its tolerability was inferior. Besides, the tolerability of SSRI and TCA was inferior to placebo. Conclusions:CBT combined with medications is more effective than BZD alone and the antidepressants alone. CBT combined with medications may selected the first-line treatment for panic disorder.