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.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To analyze differences in the intestinal microbiota and transcriptomics between N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)gastric cancer rats and normal rats and to analyze the correlation between the two,so as to provide a reference for related studies using MNNG gastric cancer rats as a model.Methods A total of 12 Wistar rats were randomly divided into normal(NM)and gastric cancer(GC)groups.The GC group was given a concentration of 20 mg/mL of MNNG by gavage with a dose of 100 g/mL once a day,and the NM group was given the same amount of normal saline by gavage.Samples were collected for testing after 16 weeks of continuous intervention.The gastric tissues were collected and stained by HE staining to observe morphological changes in the gastric mucosa of the two groups,and the expression levels of differential genes were detected by transcriptome sequencing.The cecal contents were collected for 16S rRNA sequencing.Results(1)Visual observation and HE results showed that the volume of gastric mucosa in the NM group was normal,the surface was glossy,the gastric wall was elastic,the direction of the mucosal folds was regular,there were no hyperplasia or hemorrhagic spots.In the GC group,the volume of gastric mucosa was reduced,the gastric wall was thinned,elasticity was poor,the direction of the folds was disordered and irregular,and there was a bulge accompanied by yellow-black keratotic hyperplasia.In the NM group,the squamous epithelial layer,submucosa,and muscular layer of the gastric mucosa were clear,with no hyperplasia and keratinization.In the GC group,the gastric mucosa had disorganized layers and cell polarity,with different cell morphologies;the squamous epithelial layer was destroyed,and squamous epithelial cells were hyperplasic,keratinized,and had invaded the muscular layer by proliferation.The modeling was considered successful.(2)The results of intestinal microbiota sequencing showed that the abundance of Akkermansia and Lactobacillus in MNNG gastric cancer rats decreased significantly,and the abundance of the rumen coccaceae Prevonella,and Blauter increased significantly.(3)The three key pathways obtained by transcriptomic sequencing and KEGG pathway enrichment analysis were amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway,and five genes differentially enriched in these three pathways were those for MCPT8I2,IGH-6,IGHG1,ACTN2,and VEGF-D.(4)Combined analysis of intestinal microbiota and transcriptomics showed that_UCG-005,Prevonella_UCG-003 and Brautella were positively correlated with amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway.Conclusions The abundance of intestinal microbiota in gastric cancer rats formed by MNNG gavage is different from that of normal rats.The genes for MCPT8I2,IGH-6,IGHG1,ACTN2 and VEGF-D may be up-regulated in gastric cancer induced by MNNG gavage.Combined analysis of intestinal microbiota and differential genes suggested that the mechanism of MNNG carcinogenesis may be mainly related to the destruction of gastric mucosa and the inflammatory response.

OBJECTIVE To observe the clinical efficacy of Zhenshi Burn Ointment on postoperative wound healing of simple anal fistula and explore its potential mechanism of action.METHODS A total of 60 patients with low-position simple anal fistula of damp-heat pouring downward type admitted to the Department of Anorectum,Nanjing Hospital of Chinese Medicine Affiliated to Nan-jing University of Chinese Medicine from May to December 2023 were selected as the research subjects and randomly divided into an experimental group and a control group,with 30 cases in each group.After surgery,the control group was given sterilized vaseline gauze for external application,and the experimental group was given Zhenshi Burn Ointment for external application.The course of treatment for both groups was 30 d.After treatment,the postoperative wound healing time,wound healing rate,pain score,wound granulation growth and secretion,and changes in TCM syndrome score were compared between the two groups.The pathological sec-tions of wound granulation tissue were compared 14 d after surgery.The transcription levels of COL1A1,type Ⅲ collagen(COL3A1),epidermal growth factor(EGF),and fibroblast growth factor(FGF2)in granulation tissue were detected by qPCR.The expression lev-els of proteins related to MEK/ERK signaling pathway were detected by Western blot.RESULTS Compared with the control group,the wound healing rates of the experimental group were significantly increased at 7,14,21,and 30 d after surgery(P<0.01),and the wound healing time was significantly shortened(P<0.01).At 7 d after surgery,the pain score of the experimental group was signifi-cantly lower than that of the control group(P<0.05).At 7 and 14 d after surgery,the granulation growth score of the wound in the ex-perimental group was significantly lower than that of the control group(P<0.01).At 14 d after surgery,the secretion score of the ex-perimental group was significantly lower than that of the control group(P<0.01).At 14 and 30 d after surgery,the total score of TCM syndrome in the experimental group was significantly better than that in the control group(P<0.05).At 14 d after surgery,the patho-logical improvement of granulation tissue in the wound in the experimental group was better than that in the control group,and the con-tent of collagen fiber and type I collagen(Collagen I)was significantly higher than that in the control group(P<0.01).The mRNA contents of COL1A1,COL3A1,EGF,and FGF2 were significantly higher than those in the control group(P<0.05,P<0.01);the levels of p-MEK1/2 and p-ERK1/2 proteins were higher than those in the control group(P<0.05).CONCLUSION Zhenshi Burn Ointment has a good effect on promoting postoperative anal fistula wound healing,which may be related to upregulating growth factor expression,promoting collagen regeneration,and activating MEK/ERK pathway.

Objective To investigate alterations in interhemispheric functional connectivity(FC)in the cerebral cortices connected via the corpus callosum in patients with Alzheimer's disease(AD),and to explore their relationships with cognitive function and activities of daily living.Methods Resting-state functional magnetic resonance imaging data were collected from 28 patients with Alzheimer's dementia(d-AD),47 patients with mild cognitive impairment(MCI),and 37 healthy controls(HC).Using a trancallosal tract template,32 pairs of homologous cortical brain regions directly connected to 32 subregions of the corpus callosum were selected as regions of interest for interhemispheric FC analysis.Further correlation analyses were performed between FC values in patient groups and their scores on the Montreal Cognitive Assessment-Basic(MoCA-B)Scale and the Activities of Daily Living(ADL)Scale.Results Compared with HC group,both MCI and d-AD groups exhibited hyperconnectivity(significantly increased FC)in interhemispheric non-homologous brain regions.Specifically,hyperconnectivity in the MCI group was scattered across the frontal,parietal,temporal,and occipital lobes,while in the d-AD group,it was concentrated within the precentral and postcentral gyri.Notably,hyperconnectivity involving the prefrontal and occipital lobes in the MCI group showed significant declines in the d-AD group.The interhemispheric homologous FC in the d-AD group reduced more significantly than the MCI group.Additionally,in the d-AD group,2 interhemispheric FC within the prefrontal lobe(between the bilateral orbital parts of the inferior frontal gyrus,and between the left medial frontal gyrus and the right middle frontal gyrus)were correlated with MoCA-B scores,and 2 FC(between the bilateral middle occipital gyri,and between the left inferior parietal lobule and the right middle frontal gyrus)were correlated with ADL scores.Conclusion MCI and d-AD exhibit distinct patterns of interhemispheric FC alterations,and the interhemispheric FC changes in AD patients are non-progressive.The close relationships between interhemispheric homologous/non-homologous FC and MoCA-B/ADL scores in d-AD patients provide an objective basis and reference for clinical neuromodulation.

Objective To explore function-structure covariant patterns in Alzheimer's disease(AD)and mild cognitive impairment(MCI),and to investigate their associations with cognitive function and activities of daily living.Methods three-way parallel group independent component analysis(three-way pGICA),was used to identify the covariant patterns of resting-state functional MRI temporal data,gray matter density maps,and fractional anisotropy(FA)maps,and the differences between different groups were compared.Furthermore,the associations of covariant patterns with the Montreal Cognitive Assessment-Basic(MoCA_B)Scale scores and Activities of Daily Living Scale scores were analyzed.Results The function-structure covariant patterns in AD and MCI were characterized by the enhanced negative functional connectivity between the left posterior salience network and the right default mode network,the decreased gray matter density in the bilateral dorsolateral prefrontal cortex,and the reduced FA values in the left superior corona radiata(correlations:P<0.001,FDR corrected).Compared with HC group,AD group showed significant abnormalities in all identified covariant patterns(P<0.01,FDR corrected),but MCI group only exhibited a significant decrease in gray matter density in the bilateral dorsolateral prefrontal cortex(P<0.05,FDR corrected).Additionally,AD group had significantly lower FA value in the left superior corona radiata than MCI group(P<0.05,FDR corrected).The loadings reflecting the degree of covariation were significantly correlated with the Activities of Daily Living Scale scores(P<0.05,FDR corrected)but not with MoCA_B Scale scores.Conclusion The function-structure covariant patterns in AD and MCI are consistent with the declines in activities of daily living.The multimodal fusion analysis(three-way pGICA)provides a novel approach to understand the brain damage mechanisms underlying the covariant evolution of MCI and AD.

Objective To analyze differences in the intestinal microbiota and transcriptomics between N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)gastric cancer rats and normal rats and to analyze the correlation between the two,so as to provide a reference for related studies using MNNG gastric cancer rats as a model.Methods A total of 12 Wistar rats were randomly divided into normal(NM)and gastric cancer(GC)groups.The GC group was given a concentration of 20 mg/mL of MNNG by gavage with a dose of 100 g/mL once a day,and the NM group was given the same amount of normal saline by gavage.Samples were collected for testing after 16 weeks of continuous intervention.The gastric tissues were collected and stained by HE staining to observe morphological changes in the gastric mucosa of the two groups,and the expression levels of differential genes were detected by transcriptome sequencing.The cecal contents were collected for 16S rRNA sequencing.Results(1)Visual observation and HE results showed that the volume of gastric mucosa in the NM group was normal,the surface was glossy,the gastric wall was elastic,the direction of the mucosal folds was regular,there were no hyperplasia or hemorrhagic spots.In the GC group,the volume of gastric mucosa was reduced,the gastric wall was thinned,elasticity was poor,the direction of the folds was disordered and irregular,and there was a bulge accompanied by yellow-black keratotic hyperplasia.In the NM group,the squamous epithelial layer,submucosa,and muscular layer of the gastric mucosa were clear,with no hyperplasia and keratinization.In the GC group,the gastric mucosa had disorganized layers and cell polarity,with different cell morphologies;the squamous epithelial layer was destroyed,and squamous epithelial cells were hyperplasic,keratinized,and had invaded the muscular layer by proliferation.The modeling was considered successful.(2)The results of intestinal microbiota sequencing showed that the abundance of Akkermansia and Lactobacillus in MNNG gastric cancer rats decreased significantly,and the abundance of the rumen coccaceae Prevonella,and Blauter increased significantly.(3)The three key pathways obtained by transcriptomic sequencing and KEGG pathway enrichment analysis were amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway,and five genes differentially enriched in these three pathways were those for MCPT8I2,IGH-6,IGHG1,ACTN2,and VEGF-D.(4)Combined analysis of intestinal microbiota and transcriptomics showed that_UCG-005,Prevonella_UCG-003 and Brautella were positively correlated with amebiasis,systemic lupus erythematosus,and the PI3K-Akt signaling pathway.Conclusions The abundance of intestinal microbiota in gastric cancer rats formed by MNNG gavage is different from that of normal rats.The genes for MCPT8I2,IGH-6,IGHG1,ACTN2 and VEGF-D may be up-regulated in gastric cancer induced by MNNG gavage.Combined analysis of intestinal microbiota and differential genes suggested that the mechanism of MNNG carcinogenesis may be mainly related to the destruction of gastric mucosa and the inflammatory response.

OBJECTIVE To observe the clinical efficacy of Zhenshi Burn Ointment on postoperative wound healing of simple anal fistula and explore its potential mechanism of action.METHODS A total of 60 patients with low-position simple anal fistula of damp-heat pouring downward type admitted to the Department of Anorectum,Nanjing Hospital of Chinese Medicine Affiliated to Nan-jing University of Chinese Medicine from May to December 2023 were selected as the research subjects and randomly divided into an experimental group and a control group,with 30 cases in each group.After surgery,the control group was given sterilized vaseline gauze for external application,and the experimental group was given Zhenshi Burn Ointment for external application.The course of treatment for both groups was 30 d.After treatment,the postoperative wound healing time,wound healing rate,pain score,wound granulation growth and secretion,and changes in TCM syndrome score were compared between the two groups.The pathological sec-tions of wound granulation tissue were compared 14 d after surgery.The transcription levels of COL1A1,type Ⅲ collagen(COL3A1),epidermal growth factor(EGF),and fibroblast growth factor(FGF2)in granulation tissue were detected by qPCR.The expression lev-els of proteins related to MEK/ERK signaling pathway were detected by Western blot.RESULTS Compared with the control group,the wound healing rates of the experimental group were significantly increased at 7,14,21,and 30 d after surgery(P<0.01),and the wound healing time was significantly shortened(P<0.01).At 7 d after surgery,the pain score of the experimental group was signifi-cantly lower than that of the control group(P<0.05).At 7 and 14 d after surgery,the granulation growth score of the wound in the ex-perimental group was significantly lower than that of the control group(P<0.01).At 14 d after surgery,the secretion score of the ex-perimental group was significantly lower than that of the control group(P<0.01).At 14 and 30 d after surgery,the total score of TCM syndrome in the experimental group was significantly better than that in the control group(P<0.05).At 14 d after surgery,the patho-logical improvement of granulation tissue in the wound in the experimental group was better than that in the control group,and the con-tent of collagen fiber and type I collagen(Collagen I)was significantly higher than that in the control group(P<0.01).The mRNA contents of COL1A1,COL3A1,EGF,and FGF2 were significantly higher than those in the control group(P<0.05,P<0.01);the levels of p-MEK1/2 and p-ERK1/2 proteins were higher than those in the control group(P<0.05).CONCLUSION Zhenshi Burn Ointment has a good effect on promoting postoperative anal fistula wound healing,which may be related to upregulating growth factor expression,promoting collagen regeneration,and activating MEK/ERK pathway.

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed

OBJECTIVE: To explore the application value of infrared thermography in the design and harvesting of ultrathin anterolateral thigh perforator flaps. METHODS: Between June 2024 and December 2024, 9 cases of ultrathin anterolateral thigh perforator flaps were designed and harvested with the assistance of infrared thermography. There were 7 males and 2 females, aged 21-61 years (mean, 39.8 years). The body mass index ranged from 19.49 to 26.45 kg/m² (mean, 23.85 kg/m²). Causes of injury included 5 cases of traffic accident injuries and 4 cases of machine crush injuries. There were 3 cases of leg wounds, 2 cases of foot wounds, and 4 cases of hand wounds. After debridement, the size of wound ranged from 7 cm×4 cm to 13 cm×11 cm. The time from admission to flap repair surgery was 5-12 days (mean, 7 days). Preoperatively, perforator localization was performed using a traditional Doppler flow detector and infrared thermography, respectively. The results were compared with the actual intraoperative locations; a discrepancy ≤10 mm was considered as consistent localization (positive), and the positive predictive value was calculated. All 9 cases were repaired with ultrathin anterolateral thigh perforator flaps designed and harvested based on thermographic images. The size of flap ranged from 8 cm×5 cm to 14 cm×8 cm, with a thickness of 3-6 mm (mean, 5.2 mm). One donor site was repaired with a full-thickness skin graft, and the others were sutured directly. Postoperatively, anti-inflammatory, anticoagulant, and anti-vascular spasm treatments were administered, and follow-up was conducted. RESULTS: The Doppler flow detector identified 22 perforating vessels within the set range, among which 16 were confirmed as superficial fascia layer perforators intraoperatively, with a positive predictive value of 72.7%. The infrared thermograph detected 23 superficial fascia layer perforating vessels, and 21 were verified intraoperatively, with a positive predictive value of 91.3%. There was no significant difference between the two methods [OR (95%CI)=3.93 (0.70, 22.15), P=0.100]. The perforator localization time of the infrared thermograph was (5.1±1.3) minutes, which was significantly shorter than that of the Doppler flow detector [(10.1±2.6) minutes; MD (95%CI)=-5.00 (-7.08, -2.91), P<0.001]. Postoperatively, 1 case of distal flap necrosis healed after dressing change; all other flaps survived successfully. The skin grafts at donor site survived, and all incisions healed by first intention. All patients were followed up 3-6 months (mean, 4.7 months). No pain or other discomfort occurred at the donor or recipient sites. All patients with foot wounds could walk with shoes, and no secondary flap revision was required. Flaps in 3 hand wound cases, 2 foot wound cases, and 3 leg wound cases recovered light touch and pressure sensation, but not pain or temperature sensation; the remaining 2 cases had no sensory recovery. CONCLUSION Preoperative localization using infrared thermography for repairing ultrathin anterolateral thigh perforator flaps can help evaluate the blood supply status of perforators, reduce complications, and improve surgical safety and flap survival rate.
Humans ; Perforator Flap/blood supply* ; Adult ; Male ; Thermography/methods* ; Female ; Thigh/blood supply* ; Middle Aged ; Plastic Surgery Procedures/methods* ; Tissue and Organ Harvesting/methods* ; Infrared Rays ; Skin Transplantation/methods* ; Soft Tissue Injuries/surgery* ; Young Adult