ObjectiveTo explore the ethical issues and coping strategies in the diagnosis and treatment of 46, XY disorders of sex development （46, XY DSD） under a multidisciplinary team （MDT） model， and to deepen the understanding of relevant ethical issues while accumulating experience. MethodsA retrospective collection was conducted on the data of children with 46, XY disorders of sex development under a single-center MDT model from January 2017 to December 2024， and the ethical issues involved in the diagnosis and treatment process were analyzed. ResultsA total of 24 MDT discussion documents involving 20 children were collected， including 17 with female social gender and 3 with male social gender. The age ranged from 0.5 to 15.8 years， with children under 8 years accounting for 75%. The ethical issues primarily involved how to ensure adequate informed consent， whether surgery was necessary and its timing， and whether gender selection is reasonable and its timing. Among the 10 children raised as females who completed the gender role psychological scale assessment， 5 demonstrated masculine tendencies， all of whom had pathogenic genetic variants. Furthermore， only 1 patient changed the social gender to male. ConclusionThe diagnosis and treatment of 46, XY DSD is relatively complex， requiring multidisciplinary collaboration. This process involves numerous ethical issues and necessitates adhering to medical ethical principles. Ensuring adequate informed consent is crucial， especially for younger children. The surgery and its timing selection must adhere to the principles of beneficence， non-maleficence， and leaving room for the future. Gender selection constitutes a focus and challenge in diagnosis and treatment. Psychological scales and genetic etiologies are conducive to judgments regarding gender selection， yet multiple factors in the real world may interfere with the gender selection.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To understand the relationship between sleep duration and cardiovascular and metabolic comorbidities (CMM) in middle-aged and elderly people in China.Methods:This study was a prospective cohort study, based on the data of China Health and Retirement Tracing Survey (CHARLS) from 2011 to 2015, and included middle-aged and elderly people aged≥45 years in the cohort study. Age, gender, marital status, residence, education, smoking status, alcohol status, body mass index, history of diabetes, history of dyslipidemia, history of hypertension, history of stroke, history of heart disease, history of mental illness, depression scale score were collected. Multivariate logistic regression was used to analyze the association between daily sleep duration and the risk of CMM onset and to construct four models with stepwise adjusted covariates. A stratified analysis was established based on demographic factors, lifestyle factors, metabolic factors, cardiovascular and cerebrovascular factors, and psychological factors. Meanwhile, a subgroup analysis was established according to different combinations of cardiovascular and metabolic diseases to explore the association between sleep length and the risk of CMM in different populations.Results:A total of 297 (4.4%) of the 6 788 included participants experienced CMM. In the multivariate logistic regression, the RR value (95% CI) for the risk of CMM for>9 h was 1.99 (1.86-2.08) and 1.78 (1.64-1.92), respectively (all P<0.001). The stratified analysis showed that the risk of CMM incidence between sleep duration<7 h and>9 h was associated in people with different age, sex, residence, smoking status, drinking status, body mass index, hypertension, hypertension, diabetes, heart disease, stroke, dyslipidemia, and depression (all P<0.05). Subgroup analysis showed that sleep duration<7 h with both diabetes, heart disease and stroke had the highest risk of CMM ( RR=1.95, 95% CI: 1.65-2.14). Conclusion:In the middle-aged and elderly group in China, there is a U-shaped association between sleep duration and CMM, that is, insufficient or too long sleep duration throughout the day is related to the increased risk of CMM.

Objective To observe the clinical efficacy of lumbar disc resection under unilateral biportal endoscopy(UBE)for calcified lumbar disc herniation(CLDH).Methods A retrospective analysis was conducted on 25 patients with single-segment CLDH who underwent lumbar disc resection under UBE from January 2020 to January 2022.The operation time,postoperative hospital stay,and postoperative complications were recorded.The visual analogue scale(VAS)score for low back and leg pain,Japanese Orthopaedic Association(JOA)score for the lumbar spine,and Oswestry disability index(ODI)were used to evaluate the efficacy before surgery,3 d after surgery,1 month after surgery,and at the last follow-up.At the last follow-up,the modified Macnab standard was used to assess the excellent and good rate.Results The patients were followed up for 12～24 months,with an average of(15.60±2.60)months.The average operation time was(58.67±10.73)min,and the postoperative hospital stay was(4.65±0.63)d.The VAS score,and ODI were lower,and JOA score was higher at 3 d after surgery,1 month after surgery,and the last follow-up compared with those before surgery,and the differences were statistically significant(P<0.05).At the last follow-up,according to the modified Macnab criteria,15 cases were rated as excellent,9 cases as good,and 1 case as fair.The excellent and good rate was 96.00%(24/25).Postoperative complications included a tear of the ventral dural sac of the nerve root,about 5 mm in length,without dural sac repair.The patient was instructed to stay in bed for 5 d after surgery and was given fluid replacement.The patient did not complain of discomfort such as headache when he got out of bed,and the postoperative MRI showed no massive epidural effusion.One patient had lower limb sensory disturbance and was treated with neurotrophic drugs,and recovered at the 1-month follow-up after surgery.Postoperative imaging examinations showed that the free calcified tissues were basically completely resected and the nerve roots were adequately decompressed.At the last follow-up,no recurrent cases were found.Conclusion Lumbar disc resection under UBE for CLDH is an effective and safe minimally invasive technique.

Clinical pharmacist teacher training is an important mean to improve the quality of clinical pharmacy talent cultivation and ensure the service ability and level of the clinical pharmacist team.The Pharmacy Administration and Pharmacy Practice in Healthcare Institutions-Part 4-8-2:Pharmacy Administration-Pharmacy Training Management-Clinical Pharmacist Teacher Training was based on the newly revised management document for clinical pharmacist teacher training of the Chinese Hospital Association.After sorting out relevant materials,such as standards,policies and regulations,technical specifications,liter-ature,documents of the Chinese Hospital Association,expert opinions,and the current situation of clinical pharmacist teacher training in China,the standard was formulated.In the standard,12 key elements,which can be divided into 3 parts of base manage-ment,training process and assessment,quality management and evaluation improvement,were standardized.This article aimed to introduce the construction method and content of the standard,to facilitate the understanding of the standard content for medical institutions which joined or willing to join the clinical pharmacist teacher training base,and to provide a reference for other medi-cal institutions to carry out related work.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

ObjectiveTo preliminarily explore the active components and target pathways of Angelicae Sinensis Radix-Polygonati Rhizoma （ASR-PR） herb pair in the treatment of simple obesity through network pharmacology and molecular docking， and to verify and investigate its mechanism of action via animal experiments. MethodsThe chemical constituents and targets of ASR and PR were predicted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Targets related to simple obesity were identified by retrieving the GeneCards， Online Mendelian Inheritance in Man （OMIM）， Pharmacogenomics Knowledgebase （PharmGKB）， and DisGeNET databases. The intersection of drug and disease targets was used to construct an active component-target network using Cytoscape software. This network was imported into the STRING database to construct a protein-protein interaction （PPI） network， and topological analysis was conducted to identify core genes. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis and mapping were performed using the DAVID database and the Microbioinformatics platform. AutoDock 1.5.7 software was used to perform molecular docking between the top five active components and core targets. An animal model of simple obesity was established by feeding C57BL/6J mice a high-fat diet. The mice were administered ASR （2.06 g·kg^-1）， PR （2.06 g·kg^-1）， or ASR-PR （4.11 g·kg^-1） for 10 weeks， while the model group received an equal volume of purified water by gavage. After the administration period， the mice were sacrificed to measure body fat weight and serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. Hematoxylin-eosin （HE） staining was used to observe histopathological sections of liver and adipose tissue. Serum levels of leptin， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA expression levels of epidermal growth factor receptor （EGFR） and signal transducer and activator of transcription 3 （STAT3） in liver tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsNetwork pharmacology and molecular docking results indicated that the treatment of simple obesity by ASR-PR may involve the regulation of protein expression of core targets EGFR and STAT3 by its main components MOL009760 （Siberian glycoside A_qt）， MOL003889 （methyl protodioscin_qt）， MOL009766 （resveratrol）， MOL006331 （4′，5-dihydroxyflavone）， and MOL004941 （baicalin）， thereby modulating the PI3K/Akt and JAK/STAT signaling pathways. The animal experiment results showed that compared with the normal group， the model group had significantly increased body weight， body fat weight， and serum levels of TG， TC， TNF-α， IL-6， and leptin （P<0.01）. EGFR mRNA expression was significantly elevated （P<0.05）， while STAT3 mRNA expression was significantly decreased （P<0.01）. Histological analysis revealed disordered hepatic architecture in the model group， with pronounced lipid vacuoles， cytoplasmic loosening， lipid accumulation， and steatosis. Adipocytes in white adipose tissue （WAT） and brown adipose tissue （BAT） of the model group exhibited markedly increased diameters， reduced cell counts per unit area， and irregular morphology. Compared with the model group， the ASR-PR group significantly reduced body weight， body fat weight， serum TC， IL-6， TNF-α， leptin levels， and EGFR mRNA expression （P<0.01）. TG levels were also significantly decreased （P<0.05）， while STAT3 mRNA expression was significantly increased （P<0.01）. Histopathological improvements included reduced size and number of hepatic lipid vacuoles and restoration of liver cell morphology toward that of the normal group. The diameter of adipocytes significantly decreased， and the number of adipocytes per unit area increased. ConclusionASR-PR may regulate the expression of key target proteins such as EGFR and STAT3 via its core active components， modulate the PI3K/Akt and JAK/STAT signaling pathways， repair damaged liver and adipose tissues， and thereby alleviate the progression of obesity in mice.