Objective To investigate the effects of aloperine(ALO)on bone metabolism in osteoporosis(OP)mice via Wnt/β-catenin signaling pathway-mediated autophagy and apoptosis.Methods Sixty mice were randomly allocated into six groups(n=10 per group):Sham group(sham-operated mice),OP group(osteoporosis model induced by bilateral ovariectomy),L-ALO group(OP mice intraperitoneally injected with 10 mg/kg aloper-ine),M-ALO group(OP mice intraperitoneally injected with 20 mg/kg aloperine),H-ALO group(OP mice intra-peritoneally injected with 30 mg/kg aloperine),and EV group(OP mice administered 0.09 mg/kg estradiol valerate).Bone mineral density and microstructure of the tibia were assessed.Hematoxylin and eosin(HE)staining was per-formed to examine the morphology of tibial bone tissue.Serum levels of OCN,OPG,ALP,Ca,and P were measured using ELISA.Protein expression levels of LC3-Ⅱ,LC3-Ⅰ,Beclin-1,P62,Caspase-3,Caspase-9,Bax,Wnt3a,β-catenin,and C-Myc were analyzed by Western blot.Autophagosomes were visualized using immunofluorescence.Results Compared with the Sham group,the bone mineral density(BMD)and trabecular thickness in the OP group were significantly reduced,while trabecular separation,bone surface area,and volume were significantly increased(P<0.05).The levels of OPG,OCN,Ca,and P were significantly downregulated,whereas ALP levels were significantly upregulated(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly decreased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly increased(P<0.05).Compared with the OP group,the L-ALO,M-ALO,and H-ALO groups exhibited significant increases in BMD and trabecular thickness,along with significant decreases in trabecular separation,bone surface area,and volume(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).In contrast,compared with the OP group,the EV group showed significant increases in BMD and trabecular thickness,as well as significant decreases in trabecular separation,bone surface area to volume ratio(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).Conclusions Peanine may promote autophagy in osteoblasts and inhibit their apoptosis,thereby improving bone metabolism in OP mice.This effect may be mediated through the activation of the Wnt/β-catenin signaling pathway.

Objective To investigate the effects of aloperine(ALO)on bone metabolism in osteoporosis(OP)mice via Wnt/β-catenin signaling pathway-mediated autophagy and apoptosis.Methods Sixty mice were randomly allocated into six groups(n=10 per group):Sham group(sham-operated mice),OP group(osteoporosis model induced by bilateral ovariectomy),L-ALO group(OP mice intraperitoneally injected with 10 mg/kg aloper-ine),M-ALO group(OP mice intraperitoneally injected with 20 mg/kg aloperine),H-ALO group(OP mice intra-peritoneally injected with 30 mg/kg aloperine),and EV group(OP mice administered 0.09 mg/kg estradiol valerate).Bone mineral density and microstructure of the tibia were assessed.Hematoxylin and eosin(HE)staining was per-formed to examine the morphology of tibial bone tissue.Serum levels of OCN,OPG,ALP,Ca,and P were measured using ELISA.Protein expression levels of LC3-Ⅱ,LC3-Ⅰ,Beclin-1,P62,Caspase-3,Caspase-9,Bax,Wnt3a,β-catenin,and C-Myc were analyzed by Western blot.Autophagosomes were visualized using immunofluorescence.Results Compared with the Sham group,the bone mineral density(BMD)and trabecular thickness in the OP group were significantly reduced,while trabecular separation,bone surface area,and volume were significantly increased(P<0.05).The levels of OPG,OCN,Ca,and P were significantly downregulated,whereas ALP levels were significantly upregulated(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly decreased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly increased(P<0.05).Compared with the OP group,the L-ALO,M-ALO,and H-ALO groups exhibited significant increases in BMD and trabecular thickness,along with significant decreases in trabecular separation,bone surface area,and volume(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).In contrast,compared with the OP group,the EV group showed significant increases in BMD and trabecular thickness,as well as significant decreases in trabecular separation,bone surface area to volume ratio(P<0.05).The levels of OPG,OCN,Ca,and P were significantly upregulated,while ALP levels were significantly downregulated(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio and expression levels of Beclin-1,Wnt3a,β-catenin,and C-Myc proteins were significantly increased,while the expression levels of P62,Caspase-3,Caspase-9,and Bax proteins were significantly decreased(P<0.05).Conclusions Peanine may promote autophagy in osteoblasts and inhibit their apoptosis,thereby improving bone metabolism in OP mice.This effect may be mediated through the activation of the Wnt/β-catenin signaling pathway.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Objective:To explore the clinical effects of free anterolateral thigh perforator flaps in repairing diabetic foot ulcers (DFUs) under a multi-disciplinary team (MDT) cooperation model.Methods:The study was a retrospective observational study. From June 2018 to December 2022, 49 DFU patients who met the inclusion criteria were admitted to the Department of Hand and Foot Microscopy and Wound Repair Surgery of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), including 28 males and 21 females, aged from 47 to 68 years, with type 2 diabetes history period ranging from 6 months to 21 years. Under a MDT cooperation model, the physicians from department of endocrinology comprehensively assessed the patients, stabilized the patients' general condition, and controlled their complications, the surgeons from department of vascular surgery assessed and improved the patients' lower limb blood supply, the physicians from department of infectious diseases provided anti-infection treatment plans, the physicians from department of anesthesiology and perioperative medicine assessed the patients' perioperative risk and ensured their perioperative safety, and according to the patients' condition, the physicians from departments such as cardiology, neurology, nutrition, and rehabilitation actively and timely participated in the treatment. The surgeons from department of hand and foot microscopy and wound repair surgery prepared the wound base and used free anterolateral thigh perforator flaps to repair the wounds. After once or multiple debridement in the first stage, the wound area ranged from 5.0 cm×4.5 cm to 17.0 cm×10.0 cm. After once or twice vacuum sealing drainage treatment, the free anterolateral thigh perforator flaps were used to repair the wounds with incision area of 6 cm×5 cm to 18 cm×11 cm in the second stage. The descending branches of lateral circumflex femoral artery and the accompanying veins of flaps were anastomosed to the arteries and veins in the recipient sites, respectively. The wounds in the flap donor sites were sutured directly. After surgery, whether the patient's perioperative period was stable, the survival of flaps, the healing of wounds in the flap donor and recipient sites were observed. During the follow-up, the texture and appearance of flaps, whether there was a new ulcer, and the patient's walking ability were observed.Results:All the patients had stable perioperative period. Among them, the flaps in 46 patients survived successfully; the flaps in 2 patients developed complete necrosis, including 1 case whose ulcer was healed after repair of pedicled flap from the lower leg, and 1 case who underwent amputation of the lower leg; the flap in 1 patient developed partial necrosis, which was healed after dressing change and skin grafting. The wounds in the flap donor and recipient sites healed well. During the postoperative follow-up of 6-24 months, the flaps had good texture and appearance with no new ulcers, and the patients had no obvious impairment in daily walk.Conclusions:The MDT cooperation model can sufficiently ensure the perioperative safety of DFU patients. The free anterolateral thigh perforator flaps can repair the DFU wounds achieving good clinical effects with high flap survival rate and decreased amputation rate.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

Building a nationwide representative sibling information database of pediatric cancer is of great significance for the research of pediatric cancer. In October 2022, based on the national pediatric cancer surveillance platform, the National Center for Pediatric Cancer Surveillance(NCPCS) identified and integrated the information of pediatric cancer cases using the patient master index, and then determined and retrieved the diagnosis and treatment information of pediatric cancer siblings through the sibling pair matching algorithm system, to establish the sibling information database. The information database was stored in the sibling database module of the surveillance platform, which realized the dynamic update, retrieval, download, and analysis of sibling information. The database provided data and technical support for the further childhood cancer research among siblings, as well as provided a reference for the construction of research-oriented databases for other disease surveillance systems. As of March 2024, this database had included 2 980 childhood cancer patients, collecting nearly 30 000 related medical records. In the future, NCPCS should further improve the sensitivity of sibling decision logic and expand the functionality of the sibling information database, so as to better meet the diverse needs of clinical and scientific research.

Building a nationwide representative sibling information database of pediatric cancer is of great significance for the research of pediatric cancer. In October 2022, based on the national pediatric cancer surveillance platform, the National Center for Pediatric Cancer Surveillance(NCPCS) identified and integrated the information of pediatric cancer cases using the patient master index, and then determined and retrieved the diagnosis and treatment information of pediatric cancer siblings through the sibling pair matching algorithm system, to establish the sibling information database. The information database was stored in the sibling database module of the surveillance platform, which realized the dynamic update, retrieval, download, and analysis of sibling information. The database provided data and technical support for the further childhood cancer research among siblings, as well as provided a reference for the construction of research-oriented databases for other disease surveillance systems. As of March 2024, this database had included 2 980 childhood cancer patients, collecting nearly 30 000 related medical records. In the future, NCPCS should further improve the sensitivity of sibling decision logic and expand the functionality of the sibling information database, so as to better meet the diverse needs of clinical and scientific research.

Objective:To evaluate the feasibility of coronary artery calcium (CAC) detection, quantification and risk classification using ultra-low-dose chest CT (ULD-CT) combined with a calcium-aware algorithm.Methods:A total of 115 patients were prospectively enrolled from April to October 2022 at Zhejiang Provincial People′s Hospital, who underwent a standard calcium scoring CT (CACS-CT) scan followed by an additional ULD-CT scan. CACS-CT adopted a prospective ECG-triggered sequence scan with a tube voltage of 120 kVp, and the reconstruction algorithm with Qr36 (group CACS-CT Qr). ULD-CT adopted non-ECG-triggered high-pitch scan with a tube voltage of Sn 100 kVp, and the standard algorithm Qr36 (group ULD-CT Qr) and calcium-aware algorithm Sa36 (group ULD-CT Sa) were respectively used to reconstruct two groups of images. Taking the CAC detection of CACS-CT as a reference, the accuracy of ULD-CT for detecting CAC was calculated, and kappa was used to evaluate the agreement of CAC detection between scanning protocols. The agreement of CACS quantification between scanning protocols was assessed using intraclass correlation coefficients (ICC) and Bland-Altman plots, and the agreement of risk classification between scanning protocols was assessed using weighted kappa. Results:The CAC was found in 66.96% (77/115) of patients in CACS-CT Qr. Taking the CAC detection in CACS-CT Qr as a reference, the sensitivity of CAC detection in ULD-CT Qr and ULD-CT Sa was 96.1% and 97.4%, respectively, and the specificity was 94.73% (k= 0.902, 0.921). The CACS for ULD-CT Qr and ULD-CT Sa was lower than that for CACS-CT Qr (3.6, 6.2 vs. 8.5; P< 0.001), but strongly correlated with CACS for CACS-CT Qr ( r= 0.983, P< 0.001). The mean difference in CACS for ULD-CT Sa and CACS-CT Qr was smaller (12.33), and the agreement was better (ICC= 0.992). The agreement of risk classifications between ULD-CT Sa and CACS-CT Qr was relatively high (weighted k= 0.936), and the reclassification rate (6.08%) was relatively low. The effective radiation dose for ULD-CT was reduced by approximately 77.22% compared with that for CACS-CT. Conclusions:It is feasible to evaluate CACS using Non-ECG-triggered ULD-CT combined with a calcium-aware algorithm.

Objective:To investigate the effects of circ_000543 derived from hypoxic exosomes on proliferation and invasion of breast cancer (BC) cells.Methods:Bioinformatic website was used to predict the abnormal expression of circ_000543 in BC tissue and the transcription factor that might regulate circ_000543. Double luciferase report experiment and ChIP assay were used to confirm the regulation relationship between YY1 and circ_000543. Exosomes were separated from normal BC cells and BC cells under hypoxic condition, and qRT-PCR was adopted to detect the expression of circ_000543 in exosomes. The expression of circ_000543 and YY1 in exosomes was intervened and the exosomes were cocultured with BC cells under normoxia. CCK8 and Transwell assay was used to detect the proliferation and invasive ability individually.Results:qRT-PCR experiment found that, compared with MCF-10A cells (1±0.11) and exosomes isolated from normoxic cells (1±0.10), circ_000543 expression was up-regulated in BC cells (1.59±0.13) and exosomes derived from cells under hypoxic condition (1.63±0.12) ( t=6.001, P=0.004; t=6.986, P=0.002). Exosomes derived from cells under hypoxic condition promoted proliferation and invasion of BC cells under normoxia. Inhibition of circ_000543 partially offset the effects of exosomes. YY1 induced the expression of circ_000543 in BC cells as a transcription factor. The expression of circ_000543 was inhibited when YY1 expression was down-regulated; at the same time, down-regulation of YY1 inhibited the effects of exosomes on proliferation and invasion of BC cells. Conclusion:The transcription factor YY1 promoted proliferation and invasion of BC cells by inducing hypoxic breast cancer-derived exosomal circ_000543.

Objective:To investigate the effect of methyltransferase like 14 (METTL14) on the proliferation and invasion of breast cancer (BC) cells by regulating cyclin L2 (Cyclin L2, CCNL2) through m6A modification.Methods:Cancer tissues and paracancerous tissues of BC patients in Yantaishan hospital were collected from Aug. 2018 to Feb. 2020. The expression levels of m6A, METTL14 and CCNL2 in tissues were detected by high performance liquid chromatography/mass spectrometry (HPLC/MS) and qRT-PCR. Dual-luciferase reporter assay, qRT-PCR, and western blot were used to verify the regulatory relationship between METTL14 and CCNL2. RIP experiments verified the regulatory relationship between YTH domain-containing family protein (YTHDF2) and CCNL2. Cell viability was detected by MTT method, and cell invasion ability was detected by Transwell.Results:Compared with normal cells (0.24±0.02) and tissues (0.18±0.02) , BC cells MCF-10A (0.47±0.03, t=11.05, P<0.001) and HS-578T (0.41±0.03, t=8.17, P=0.001) and BC tissues (0.39±0.02, t=12.86, P<0.001) m6A level increased. Compared with normal tissues (1.00±0.26) (0.84±0.07) , METTL14 mRNA (1.57±0.28, t=13.50, P<0.001) and protein levels (1.66±0.11, t=10.89, P<0.001) in BC tissues were significantly increased high. Compared with the control group (100.00±10.11) (1.00±0.12) , the BC cell invasion ability (54.15±6.21, t=6.69, P=0.003) and activity (0.64±0.06, t=4.65, P=0.010) were weakened. Compared with the control group (100±11.05) (1±0.13) , the BC cell invasion ability (175.31±13.45, t=7.49, P=0.002) and activity (2.16±0.16, t=9.75, P=0.002) in the METTL14 overexpression group were enhanced, and the effects of METTL14 on cell invasion (137.41±12.64, t=3.56, P=0.024) and activity (1.64±0.15, t=5.59, P=0.005) were partially reversed after m6A inhibitor treatment change. Compared with normal tissues, CCNL2 expression was down-regulated in BC tissues, and the interaction between CCNL2 and METTL14 was confirmed. Compared with the control group (1.00±0.1) (0.64±0.05) , knockdown of METTL14 could make CCNL2 mRNA (1.67±0.05) . 0.13, t=7.08, P=0.002) and protein (1.09±0.09, t=7.57, P=0.002) were up-regulated. METTL14 knockout enhanced the stability of CCNL2 mRNA through a YTHDF2-dependent pathway, compared with sh-METTL14 group (50.47±5.16) (0.52±0.05) , BC cell invasion ability of sh-METTL14+sh-CCNL2 group (71.69±6.41, t=4.47, P=0.011) and activity (0.64±0.05, t=2.94, P=0.042) were improved. Conclusion:METTL14 inhibits the expression of CCNL2 through m6A modification to enhance the invasion and activity of BC cells.