Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Objective To investigate the survival time of patients diagnosed with sporadic Creutzfeldt-Jakob disease in China between 2020 and 2022 and explore the associated factors influencing survival.Methods A retrospective analysis was conducted on clinically diagnosed cases with complete information on sporadic Creutzfeldt-Jakob dis-ease diagnosed by the China Creutzfeldt-Jakob disease surveillance network from 2020 to 2022,baseline information of patients was obtained from the case files,telephone follow-up was used to obtain the treatment and survival status of the patients after the diagnosis,life-table method was used for estimating the survival rate,Kaplan-Meier method was used for calculating the median survival time and the 95％CI,Cox regression model was used for univariate and multivariate analyses were used to screen for factors influencing survival time.Results The median survival time of the 300 patients was 5 months(95％CI:4.165-5.835).Univariate analysis revealed that factors such as age at onset,regional distribution,presence of corticobasal or extrapyramidal symptoms as initial manifestations,number of initial symptoms,presence of corticobasal or extrapyramidal functional abnormalities,number of major clinical manifestations,presence of typical electroencephalogram findings,and use of nasal feeding during the course of the disease were potential factors influencing survival time(P＜0.1).Multivariate analysis showed that the risk of death in patients with onset age＞65 years was 1.350 times higher than in patients with onset age ≤65 years(P=0.021,95.0％CI:1.046-1.742).Patients without pyramidal or extrapyramidal dysfunction had a 0.674-fold lower risk of death compared to those with these symptoms(P=0.020,95.0％CI:0.483-0.939).Patients who did not receive nasal feeding had a 1.817-fold higher risk of death compared to those who did(P＜0.001,95.0％CI:1.406-2.349).Conclusion Age at onset,the presence of pyramidal or extrapyramidal functional abnormalities,and the use of nasal feeding during the disease course are factors influencing the survival time of pa-tients clinically diagnosed with sCJD.

With the advancement of surgical technologies and the improvement of perioperative management,the survival rates of organ transplant recipients and grafts have been significantly elevated.Shortage of donor organs has become the main obstacle to further development of organ transplantation.Recently,kidney and heart xenotransplantation with genetically modified pigs as donors have entered clinical trials and achieved favorable results.Xenotransplantation has repeatedly become a hot spot in biomedical research.Compared with heart and kidney,the survival time of liver grafts from genetically modified pigs in non-human primates is shorter.Besides,experimental results are dramatically different.Hence,it is not eligible for clinical trials.Consequently,recent research progress in xenotransplantation was reviewed from surgical pattern selection,coagulation dysfunction and acute vascular rejection,advances in liver xenotransplantation were summarized,and the main problems hindering xenotransplantation from entering clinical trials and potential solutions were illustrated,aiming to provide reference for xenotransplantation from scientific research to clinical application.

With the development of more and more multi-center and cross-field cooperative medical research,the establishment of high-quality and efficient ethical collaborative review and mutual recognition systems is an inevitable demand for multi-institutional research,and an inevitable move to implement relevant national policies.Based on the work practice of ethical collaborative review and mutual recognition in Shenzhen,by analyzing the practical challenges of ethical collaborative review and mutual recognition in China,this paper proposed that to ensure the homogeneity and efficiency of review.Government departments need to take the lead,establish an ethical review alliance,and clarify responsibilities and rights.Based on actual needs,system first,and effective communication,ethical collaborative review and mutual recognition of results could be jointly promoted,aiming to provide a reference for our counterparts in China to promote ethical collaborative review and mutual recognition of cross-institutional research.

In fixed prosthodontics, clear exposure of the preparation margin is the prerequisite for obtaining accurate digital impressions and improving the marginal fit of restorations. To resolve the issues associated with the cord retraction technique, such as pain, acute injury, and prolonged procedural time, this study proposes a new technology for intraoral digital impression taking with pneumatic gingival retraction. The new scanning head blows a high-speed airflow that instantaneously separates the free gingiva, locally exposing the subgingival preparation margin. Combined with the farthest point preservation stitching algorithm based on the distance from the normal vector and high-speed laser scanning photography, it achieves global preparation edge data and gingival reconstruction, realizing painless, non-invasive, and efficient precise acquisition of the preparation margin. Using this new technique, a patient with a full porcelain crown restoration on a posterior tooth was treated. The digital impression revealed a clear margin of the preparation, and the crown made from this data has a good marginal fit.

Objective:To understand the medical care of patients with sporadic Creutzfeldt-Jakob disease in China and its relationship with survival time.Methods:A retrospective analysis was performed on data of 150 patients with sporadic Creutzfeldt-Jakob disease diagnosed by China′s Creutzfeldt-Jakob Disease Surveillance Network during the period of January 1, 2021 to December 31, 2022 in this study, and telephone follow-up with family members was used to obtain information of the patients′ care, treatment, and survival after diagnosis. Survival was estimated by life table method, median survival time and 95% confidence interval ( CI) were calculated by Kaplan-Meier method, log-rank method was used to compare the difference in survival time between different groups, and multifactorial analysis was performed by COX proportional risk regression model regarding the influencing factors on patients′ survival time. Results:The median survival time of 150 patients with sporadic Creutzfeldt-Jakob disease was 6 months, and the cumulative lifetime survival rates at 2, 6, 12, and 18 months were 62%, 39%, 22%, and 9%, respectively. The result of univariate analysis showed that the differences in survival time between groups with the presence or absence of cortical blindness in the first symptom, the presence or absence of respiratory support (oxygen therapy), the presence or absence of adjunctive medication, and the presence or absence of tube feeding (nasogastric) were meaningful ( P<0.1). Multifactorial COX regression analysis showed that the risk of death in patients without adjuvant medication was 1.429 times higher than that in patients with adjuvant medication (95.0% CI: 1.014-2.014), and the risk of death in patients without tube feeding (nasal feeding) was 1.479 times higher than that in patients with tube feeding (nasal feeding) (95% CI: 1.052-2.081). Conclusions:Whether or not adjuvant medication is administered and whether or not tube feeding (nasogastric) is used are factors that affect survival time in patients with sporadic Creutzfeldt-Jakob disease, and the administration of appropriate adjuvant medication and tube feeding (nasogastric) may contribute to prolonging survival time in patients with sporadic Creutzfeldt-Jakob disease.

Objective:To explore the application value of optical surface monitoring system (OSMS) volume rendering technique (VRT) body surface imaging in intensity-modulated radiotherapy for thoracic tumors.Methods:A retrospective case series study was performed. The clinical data of 65 patients with thoracic tumors treated with intensity-modulated radiotherapy at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from September 2021 to October 2022 were retrospectively analyzed. In the first treatment,after cone-beam computed tomography (CBCT) scan and correction, VRT body surface images were obtained by using OSMS. In subsequent treatment, the VRT image was used as the benchmark and the 6-dimensional bed was automatically positioned to record the 6-dimensional bed positioning value. The CBCT scan was performed to record the translation and rotation errors of left-right direction (X-axis), head-foot direction (Y-axis) and front-rear direction (Z-axis). After the calibration of the 6-dimensional automatic bed shifting, the new real-time deltas (RTD) value of digital imaging and communications in medicine (DICOM) body surface image was recorded, and the new VRT image was obtained. CBCT registration error value was defined as VRT image-guided setup error. The sum of CBCT registration error value and moving bed movement value was defined as the body surface marker line-guided setup error. The sum of CBCT registration error value and the recorded DICOM image RTD value was defined as the theoretical error of DICOM image-guided setup. The advantages and disadvantages of VRT image, body surface marker line and DICOM image-guided setup were compared and analyzed.Results:There were 42 males and 23 females in 65 patients with thoracic tumors, and the age [ M ( Q1, Q3)] was 58 years (51 years, 64 years). The linear errors [ M ( Q1, Q3)] of VRT image-guided setup in X, Y and Z axes were 0.6 mm (0.3 mm, 1.2 mm), 1.2 mm (0.5 mm, 2.4 mm) and 1.1 mm (0.5 mm, 1.9 mm); and the rotational errors were 0.4° (0.1°, 0.7°), 0.4° (0.1°, 0.6°) and 0.4° (0.2°, 0.6°). The linear errors of the marker line-guided setup were 1.6 mm (0.9 mm, 2.6 mm), 2.2 mm (1.1 mm, 3.8 mm) and 1.0 mm (0.4 mm, 1.8 mm); and the rotational errors were 0.7° (0.3°, 1.2°), 0.5° (0.2°, 0.8°) and 0.5° (0.2°, 0.8°). The linear errors of the DICOM image-guided positioning were 1.1 mm (0.6 mm, 1.9 mm), 2.1 mm (1.0 mm, 3.4 mm) and 1.3 mm (0.6 mm, 3.1 mm), and the rotational errors were 0.6° (0.2°, 1.1°), 0.7° (0.3°, 1.1°), 0.7° (0.2°, 1.1°). Compared with the marker line-guided setup, except for Z-axis linear error ( P = 0.218), the VRT-guided setup errors were low (all P < 0.001). Compared with the DICOM imaging-guided setup, the VRT image-guided setup linear error and rotational error in X-, Y- and Z-axis were low (all P < 0.01). Conclusions:VRT image-guided setup is superior to traditional body surface marker setup and DICOM imaging setup; OSMS VRT body surface imaging can effectively improve the setup accuracy and stability of intensity-modulated radiotherapy for thoracic tumors, and reduce the setup errors.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

OBJECTIVE: To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. METHODS: A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. RESULTS: The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). CONCLUSION No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.
Humans ; Mosaicism ; In Situ Hybridization, Fluorescence/methods* ; Retrospective Studies ; Karyotyping ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Karyotype ; Chromosome Banding ; Sex Chromosomes

Opioid receptor agonist-antagonists are a class of drugs which have both agonistic and antagonistic effects on opioid receptors. These drugs already on the market mainly include pentazocine， butorphanol， nalbuphine， buprenorphine， dezocine and so on. Compared with pure opioid receptor agonists such as morphine and fentanyl， these drugs have strong analgesic effects， less addictive， and less side effects such as cough， itching and respiratory depression. Due to the different tendentious effects of opioid receptor agonists-antagonists among different endogenous opioid receptors （μ， κ， δ， etc.）， different receptors of subtypes can exhibit different or even opposite effects in terms of affecting emotions and drug dependence. Therefore， the rational use of these drugs can effectively reduce the occurrence of adverse reactions and drug abuse caused by opioid drugs. With the deepening of research on various endogenous opioid receptor subtypes and related drugs in the academic community， opioid receptor agonists- antagonists have broad application space and prospects in improving adverse reactions to opioid drugs and enhancing patient drug compliance.