Organ donation by minors has long been a highly controversial topic in both legal and ethical discussions worldwide. In the United States, case law has established a case-by-case review mechanism, allowing limited room for the practice of living organ donation by minors under specific conditions. Germany, with a strong emphasis on the protection of personal dignity, adopts a more cautious stance. In China, the law clearly stipulates that living organ donors must possess full civil capacity. However, some scholars argue that under strict conditions and with adequate safeguards, minors should be allowed to donate organs in emergency medical situations. Given the limited domestic experience in this area, China should develop a protective pathway that balances scientific validity, legal compliance, and humanistic concern, in line with its national conditions, legal traditions and cultural background, all under the guidance of the principle of caution. Based on a review of China’s current organ donation system, this article examines legislative philosophies, procedural designs and ethical review mechanisms in the U.S. and Germany. From a comparative law perspective, it extracts institutional elements that could serve as references, with the aim of improving China’s legal framework for organ donation by minors.

OBJECTIVE: To investigate the genetic mechanism for adverse pregnancies due to submicroscopic chromosomal structural variants in two cases, and to provide a precise guidance for preimplantation genetic testing. METHODS: Two families who had visited Chengdu Women's and Children's Central Hospital for reproduction guidance due to recurrent miscarriages, adverse pregnancy history and abnormal genetic testing of the offspring in June and December 2023 were selected as the study subjects. Chromosomal karyotyping and optical genome mapping (OGM) were carried out on peripheral blood samples from the two couples, and preimplantation genetic testing for structural rearrangement (PGT-SR) were performed on the blastocyst trophoblasts. This study was approved by the Medical Ethics Committee of the Hospital (Ethic No.: 2023-23). RESULTS: No abnormality was found on the G-banded karyotyping analysis for both couples. The OGM results revealed that the female partner of couple 1 had a translocation between 4pter-p16.3 (3.99 Mb) and 11pter-p15.4 (2.66 Mb), whilst no abnormality was found in the male partner. Similarly, the male partner of couple 2 had a translocation between 19q13.43-qter (1.90 Mb) and 22q13.31-qter (3.34 Mb). No abnormality was found in the female partner of couple 2. Neither breakpoints nor the adjacent region had involved an OMIM gene, except the formation of a fusion gene ZIM2-AS1-Z82186.1 (Both genes are non-coding, and the fusion gene was deemed as variant of unknown significance). PGT-SR of 11 blastocysts derived from couple 1 revealed that one embryo was suitable for priority transfer, three embryos were suitable for transfer, one embryo was recommended for genetic counselling, and six embryos were unsuitable for the transfer. For couple 2, six blastocysts were tested, of which only one embryo was deemed suitable for transfer. CONCLUSION When genetic testing of offspring indicates copy number variations such as deletions, duplications or mosaicism, the high-resolution OGM technique can be selected to screen parents for submicroscopic chromosomal structural variations. The result can facilitate accurate assessment for the risk of recurrence in offspring, selection of suitable method for reproduction, and identifying targets for PGT.
Humans ; Female ; Pregnancy ; Adult ; Male ; Karyotyping ; Chromosome Aberrations ; Abortion, Habitual/genetics* ; Preimplantation Diagnosis ; Genetic Testing

Objective Observational studies have shown an association between Parkinson disease （PD） and mental illness， but further studies are needed to explore the causal relationship between them. This study aims to investigate such causal relationship using the method of two-sample Mendelian randomization （MR）. Methods Related data were extracted from GWAS， and summary statistics associated with PD， depression， sleep disorders， and anxiety phenotype-variants were obtained. Single nucleotide polymorphisms （SNPs） for PD were selected as instrumental variables， and MR-PRESSO was used to exclude outliers. Inverse variance weighting was used as the main method to assess causal effect estimates， and MR Egger， weighted median， simple mode， and weighted mode were used to verify the robustness of the findings. A sensitivity analysis was used to validate the reliability of the results， including the Cochran Q test， the MR-Egger intercept test， funnel plots， and the leave-one-out method. Results A total of 21 SNPs associated with PD were identified. The MR analysis showed that PD had a causal relationship with depression （OR=0.974，95%CI 0.934‒1.015， P=0.210）， sleep disorders （OR=1.056， 95%CI 0.970-1.149， P=0.211）， and anxiety （OR=0.998， 95%CI 0.996‒1.001， P=0.118）， with no statistical significance. Different MR analyses and sensitivity analyses showed that PD did not directly contribute to the development of mental illness. Conclusion There is no direct causal relationship between PD and depression/sleep disorders/anxiety. In clinical practice， healthcare professionals should pay attention to the mental health of patients with PD. Randomized controlled studies should be conducted in the future to further validate the results of this study.
Depression ; Anxiety

Breast cancer is recognized as the most common cancer in women globally, posing a serious threat to women′s health. The treatment of breast cancer proves diverse and complex, with radiotherapy serving as a crucial treatment modality. Notably, preoperative radiotherapy holds considerable potential for improving the prognosis of patients. With the advancement in radiotherapy technology, there is a need to re-examine the clinical significance of preoperative radiotherapy for breast cancer and to further explore its applications in clinical treatment. This review provides the current status of research on preoperative radiotherapy for breast cancer, aiming to provide a reference for the radiotherapy of breast cancer.

This study sought to evaluate the efficacy and safety of venetoclax (Ven) in combination with tyrosine kinase inhibitors (TKI) and reduced-dose chemotherapy for the treatment of patients with minimal residual disease (MRD) -positive and relapsed/refractory (R/R) Ph-positive acute lymphoblastic leukemia (Ph + ALL). A retrospective analysis was conducted on the clinical data of 13 patients with MRD-positive and relapsed Ph + ALL admitted between July 2015 and February 2024 at the Affiliated Cancer Hospital of Zhengzhou University. The cohort included seven males and six females, with a median age of 50 years (range: 37-71 years). Reinduction therapy consisted of Ven and TKI administration combined with reduced-dose chemotherapy. Among the 13 patients, 10 were MRD-positive, and three had R/R disease. Of the MRD-positive group, nine (90%) achieved complete molecular response (CMR), with a median time to response of 47 days (range: 30-80) ; one patient did not respond. Among the three patients who had R/R, two (66.6%) achieved complete remission, while one patient was nonresponsive. The median overall survival (OS) and relapse-free survival (RFS) time for the entire cohort were 21.5 months and 7 months, respectively. In patients who achieved CMR, the median OS and RFS time were 35 months and 34 months, respectively. Grade ≥3 hematologic adverse events occurred in five patients (38.4%) ; however, hematopoietic function recovered in all cases, and no grade ≥3 infections or organ-related adverse reactions were observed. These findings suggest that Ven combined with TKI and reduced-dose chemotherapy may be an effective and tolerable therapeutic strategy for MRD-positive and R/R Ph + ALL, particularly in significantly improving MRD clearance rates.

When artificial intelligence is integrated into medical decision-making,the ambiguous definition of technological autonomy and the multi-party game of responsibility allocation lead to legal disputes over rights and responsibilities as well as ethical challenges.Focusing on clinical diagnosis,treatment strategy generation,and prognosis assessment,this paper reveals the data bias and decision traceability deficiencies caused by the"black box"of algorithms,and then proposes solutions from 3 dimensions:defining responsible parties,standardizing technical defect assessments,and promoting interdisciplinary collaboration.From a legal perspective,based on the"high-risk system"classification under the European Union Artificial Intelligence Act and no-fault liability principle under the product liability relative laws,a 3-tier responsibility framework of developer-operator-medical institution is constructed:for auxiliary systems,operating physicians bear ultimate responsibility;for decision-making systems,developers are required to provide verifiable algorithms and take joint liability.Ethically,dynamic review mechanisms(such as mandatory disclosure of decision tree logic and data balance metrics)are suggested to balance technological efficiency with patients' right to informed consent.

Objective To investigate the role of transcription factor EB(TFEB)in endotoxin-tolerant macrophages.Methods The RAW264.7 cells were divided into blank group(DMEM medium),LPS 5 group(5 ng/mL LPS treatment for 4 h),LPS 100 group(100 ng/mL LPS treatment for 4 h),and tolerance group(5 ng/mL LPS for 12 h followed by 100 ng/mL LPS for 4 h).The releases of inflammatory factors TNF-α and IL-6 were measured using ELISA.Western blotting and immunofluorescence assay were used to evaluate the distribution of autophagy-related proteins LC3 and P62,as well as TFEB in the cytoplasm and nucleus.Lentiviral overexpression of TFEB or siRNA-mediated knockdown of TFEB were performed to observe the changes in autophagy levels and bacterial clearance ability in the tolerant cells.Results The cells in the tolerance group had significantly lower contents of TNF-α and IL-6,as well as reduced bacterial clearance ability(P<0.01),down-regulated LC3 expression while up-regulated P62 level,and decreased expression of TFEB in both the cytoplasm and nucleus(P<0.01)when compared with the cells of the LPS 100 group.Overexpression of TFEB significantly increased LC3 level,reduced P62 level,and enhanced bacterial clearance ability in the endotoxin-tolerant cells(P<0.01).In contrast,siRNA-mediated knockdown of TFEB had no significant impacts on LC3 and P62 expression levels or bacterial clearance ability.Conclusion Overexpression of TFEB can restore the autophagy of endotoxin-tolerant cells and enhance their bacterial clearance capacity,thereby alleviating the immunosuppressive state of sepsis.These findings suggest that TFEB holds promise as a potential therapeutic target for the prevention and treatment of sepsis.

As an important setting for the administration of vaccinations, the reasonable setting up and standardized management of vaccination clinics will enhance immunization service quality, public satisfaction, and improve the vaccination rate to protect people′s health. In recent years, various provinces in China are continuously promoting the standardized construction and management of vaccination clinics. However, the level of standardization management remains unbalanced, and the capacity of vaccination services needs to be further improved. This paper reviews the standardized management process of vaccination clinics, summarizes the practice and achievements in various regions, and analyzes the challenges and issues during these processes, to provide reference for improving the standardized management level of vaccination clinics in the future.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Objective To investigate the role and underlying mechanism of activating transcription factor 3(ATF3)in suppressing lipopolysaccharide(LPS)-induced autophagy and inflammatory responses in macrophages.Methods Firstly,the gene expression omnibus(GEO)database was used to analyze ATF3 expression in peripheral blood mononuclear cells(PBMCs)from sepsis patients,and gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways.Secondly,RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group(100 ng/mL LPS).Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization,respectively.Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance.Cleavage Under Targets and Tagmentation(CUT&Tag)sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3.Furthermore,the impact of ATF3 knockdown or overexpression on autophagy-related gene 5(ATG5),autophagy-related gene 16-like 1(ATG16L1),and autophagy levels was evaluated.Results GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients(P<0.01),and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways(P<0.01).In RAW264.7 cells,100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group(P<0.01).ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages(P<0.01),whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases,and remained bacterial clearance at a low level when compared with the conditions in the negative control(NC)group(P<0.01).CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1.Compared with the NC group,ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I,ATG5,and ATG16L1 while decreased p62 expression(P<0.01).Conversely,ATF3 overexpression inhibited the expression of LC3-II/I,ATG5,and ATG16L1(P<0.01),but had no significant effect on p62 level.Conclusion Sepsis induces elevated ATF3 expression in macrophages,and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6,which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1,suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.