Objective To study the basic features,judicial identification and trial characteristics of medical malpractice cases related to gastrointestinal endoscopy,enhance the awareness of risks of gastrointestinal endoscopy among medical staffand patients.,emphasize the importance of preoperative education and provide judicial identification and trial personnel with ideas for handling such cases,ensuring standardization and consistency in handling similar cases.Methods A total of 100 medical dispute cases involving gastrointestinal endoscopy from May 2010 to May 2024 were included from the China Judgments Online database.The analysis focused on document types,years,regions,court levels,details of judicial expertise,the proportion of court decision responsibility.Results The number of cases has increased significantly since 2017,with the highest incidence in 2020 and 2021(collectively accounting for 39%);Regions with the most disputes included Fujian,Guangdong,Shandong,Shanghai,Liaoning,Beijing,Jiangsu,collectively accounting for 58%of cases.The primary method of forensic expertise was medical damage identification,accounting for 82.0%of cases;Among these,4 cases underwent reappraisal,all of which resulted in modifications to the original expertise.Male patients outnumbered female patients,with"Digestive tract discomfort"being the main reason for consultation(63%).The most common medical injury was digestive tract perforation(37%),among which colon perforation was the most common;Of the 100 cases,60 cases were found to have errors in gastrointestinal endoscopy,and the medical errors were concentrated in"Improper operation during Operation"(42 cases),The contributory roles of various negligence types in the damage consequence ranged from"no causation"to"complete causation"in varing proportions.Notably,negligence categories such as"improper intraoperative manipulation"and"delayed treatment due to untimely examination"consistently demonstrated contributory roles of"secondary causation or higher."Regarding court rulings,the majority of cases(23 cases)assigned liability proportions of 31%-50%,followed by 20 cases with liability proportions of 71%-100%.

Objective To establish a simple technical procedure for preparing doggybone DNA(dbDNA),and to discuss the distinctions in gene expression and immune response between dbDNA and conventional plasmid DNA.Induced pluripotent stem cell(iPSC)was generated from human peripheral blood mononuclear cells(PBMCs)by using dbDNA.To investigate a protocol for inserting ultra-long DNA fragments into the iPSC adeno-associated virus site 1(AAVS1),concurrently with the integration of the Cas9 expression frame point into the dbDNA-derived iPSC AAVS1 safe harbor,so as to establish a stable cell line that can achieve iPSC gene editing exclusively through the introduction of the single guide RNA(sgRNA)for the targeted gene.Methods A simple dbDNA preparation technique was established through utilization of Phi29 DNA polymerase multiple displacement amplification,protelomerase TelN digestion and covalent ligation,as well as the subsequent removal of the back-bone loop through the action of a restriction enzyme and exonuclease.The efficiency of green fluorescent protein(GFP)was eval-uated following electroporation of the dbDNA-GFP vector and the pMax-dbDNA-GFP traditional plasmid vector into PB-MCs.The mRNA expression of interferon-γ(IFN-γ)in the two groups was quantified by qPCR.The dbDNA reprogramming vectors dbDNA-MOS,dbDNA-KLF4,dbDNA-MYC and dbDNA-BCL were prepared and subsequently transferred into PBMCs to induce reprogramming.The dbDNA-iPSC cell line was identified through morphological analysis,alkaline phosphatase stai-ning,RT-PCR,and detection of pluripotent stem cell markers.The ZFN and TALEN gene editing techniques were employed to insert an 11.5 kb ultra-long DNA fragment containing the Cas9 expression cassette,EGFP reading frame with stop codons in the sequence,a eukaryotic cell screening marker and other elements at the iPSC AAVS1.The identification of the iPSC lines with Cas9 integrated into AAVS1 was conducted through the utilization of red fluorescence detection,genomic PCR reaction and Western blot.The EGFP single-strand homologous repair template and EGFP sgRNA were co-transfected into positive iPSC cell lines to repair the erroneous stop codons in the EGFP gene and to express green fluorescent protein correctly.This approach was undertaken in order to verify the gene editing ability of the Cas9 protein.Results The dbDNA vector was successfully pre-pared and employed for gene expression.The GFP gene expression efficiency of dbDNA was similar to that of traditional plas-mid DNA.The expression level of IFN-γ mRNA in the dbDNA group was lower than that of traditional plasmid DNA group.The iPSC cell lines resembling human embryonic stem cells were successfully obtained,iPSC cell lines with positive alka-line phosphatase staining,pluripotency related gene expression and stem cell pluripotency markers.The ultra-long fragment CRISPR-Cas9 gene editing reporting system was successfully inserted into the safe harbor AAVS1 site of the cell line,and the integrated fragment was successfully inserted into the genome by genomic PCR.Red fluorescent protein was expressed.Cas9 protein expression and EGFP gene recovery was confirmed by Western blot.Green fluorescence was observed.Conclusion A simple technical procedure for the preparation of dbDNA is successfully established.The gene expression efficiency of the dbD-NA vector is comparable to that of traditional plasmid DNA,with less immune response.The dbDNA-derived iPSCs are success-fully obtained,which is confirmed by morphological analysis,alkaline phosphatase staining,RT-PCR,and stem cell pluripotency markers.An 11.5 kb ultra-long DNA fragment is successfully inserted into the iPSC AAVS1 safe harbor to establish a stable iPSC cell line with Cas9-mediated gene editing.

Objective:To systematically review qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy, and to gain insights into the initiation, development, and effects of these symptoms, along with their implications for patients, to guide the creation of targeted strategies for symptom management.Methods:The qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy were performed across several databases, which included the Cochrane Library, Joanna Briggs Institute Evidence based Healthcare Center Database, PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, Wanfang Data, and Chinese Biomedical Literature Database. The retrieval period was from the establishment of the database to April 30, 2024. The studies' quality was evaluated utilizing the iteration of the Joanna Briggs Institute Qualitative Assessment and Review Instrument designed for qualitative research. Data synthesis was carried out using Meta-aggregation techniques.Results:A total of 15 articles were included and 41 results were extracted, which were grouped into 11 new categories and integrated into 3 primary themes: the manifestation of bone and joint symptoms was highly unique and varied, prominently featuring experiences such as migratory joint pain, morning stiffness, and cramps affecting both large and small joints, frequently associated with functional limitations; these symptoms significantly influence patients' everyday activities and mental health, contributing to feelings of anxiety, avoidance behaviors, fear, and a reduction in overall quality of life; to manage the intricate nature of their symptoms, patients employ a variety of coping mechanisms, such as engaging in physical activity, taking dietary supplements, consulting about medications, and seeking support from external sources.Conclusions:During endocrine therapy for breast cancer, patients exhibit diverse characteristics of musculoskeletal symptoms, and the resulting fear of recurrence, avoidance behaviors, and anxiety have a negative impact on their psychological well-being and overall health. Healthcare professionals should take into account individual differences, such as age, menopausal status, type of endocrine therapy, medication adherence, and factors that may exacerbate or alleviate symptoms, in order to effectively predict, assess, and manage bone and joint symptoms during endocrine therapy.

Objective:To systematically review qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy, and to gain insights into the initiation, development, and effects of these symptoms, along with their implications for patients, to guide the creation of targeted strategies for symptom management.Methods:The qualitative studies on the experiences of musculoskeletal symptoms in breast cancer patients undergoing endocrine therapy were performed across several databases, which included the Cochrane Library, Joanna Briggs Institute Evidence based Healthcare Center Database, PubMed, Embase, CINAHL, Web of Science, Scopus, CNKI, Wanfang Data, and Chinese Biomedical Literature Database. The retrieval period was from the establishment of the database to April 30, 2024. The studies' quality was evaluated utilizing the iteration of the Joanna Briggs Institute Qualitative Assessment and Review Instrument designed for qualitative research. Data synthesis was carried out using Meta-aggregation techniques.Results:A total of 15 articles were included and 41 results were extracted, which were grouped into 11 new categories and integrated into 3 primary themes: the manifestation of bone and joint symptoms was highly unique and varied, prominently featuring experiences such as migratory joint pain, morning stiffness, and cramps affecting both large and small joints, frequently associated with functional limitations; these symptoms significantly influence patients' everyday activities and mental health, contributing to feelings of anxiety, avoidance behaviors, fear, and a reduction in overall quality of life; to manage the intricate nature of their symptoms, patients employ a variety of coping mechanisms, such as engaging in physical activity, taking dietary supplements, consulting about medications, and seeking support from external sources.Conclusions:During endocrine therapy for breast cancer, patients exhibit diverse characteristics of musculoskeletal symptoms, and the resulting fear of recurrence, avoidance behaviors, and anxiety have a negative impact on their psychological well-being and overall health. Healthcare professionals should take into account individual differences, such as age, menopausal status, type of endocrine therapy, medication adherence, and factors that may exacerbate or alleviate symptoms, in order to effectively predict, assess, and manage bone and joint symptoms during endocrine therapy.

Objective To study the basic features,judicial identification and trial characteristics of medical malpractice cases related to gastrointestinal endoscopy,enhance the awareness of risks of gastrointestinal endoscopy among medical staffand patients.,emphasize the importance of preoperative education and provide judicial identification and trial personnel with ideas for handling such cases,ensuring standardization and consistency in handling similar cases.Methods A total of 100 medical dispute cases involving gastrointestinal endoscopy from May 2010 to May 2024 were included from the China Judgments Online database.The analysis focused on document types,years,regions,court levels,details of judicial expertise,the proportion of court decision responsibility.Results The number of cases has increased significantly since 2017,with the highest incidence in 2020 and 2021(collectively accounting for 39%);Regions with the most disputes included Fujian,Guangdong,Shandong,Shanghai,Liaoning,Beijing,Jiangsu,collectively accounting for 58%of cases.The primary method of forensic expertise was medical damage identification,accounting for 82.0%of cases;Among these,4 cases underwent reappraisal,all of which resulted in modifications to the original expertise.Male patients outnumbered female patients,with"Digestive tract discomfort"being the main reason for consultation(63%).The most common medical injury was digestive tract perforation(37%),among which colon perforation was the most common;Of the 100 cases,60 cases were found to have errors in gastrointestinal endoscopy,and the medical errors were concentrated in"Improper operation during Operation"(42 cases),The contributory roles of various negligence types in the damage consequence ranged from"no causation"to"complete causation"in varing proportions.Notably,negligence categories such as"improper intraoperative manipulation"and"delayed treatment due to untimely examination"consistently demonstrated contributory roles of"secondary causation or higher."Regarding court rulings,the majority of cases(23 cases)assigned liability proportions of 31%-50%,followed by 20 cases with liability proportions of 71%-100%.

Objective To establish a simple technical procedure for preparing doggybone DNA(dbDNA),and to discuss the distinctions in gene expression and immune response between dbDNA and conventional plasmid DNA.Induced pluripotent stem cell(iPSC)was generated from human peripheral blood mononuclear cells(PBMCs)by using dbDNA.To investigate a protocol for inserting ultra-long DNA fragments into the iPSC adeno-associated virus site 1(AAVS1),concurrently with the integration of the Cas9 expression frame point into the dbDNA-derived iPSC AAVS1 safe harbor,so as to establish a stable cell line that can achieve iPSC gene editing exclusively through the introduction of the single guide RNA(sgRNA)for the targeted gene.Methods A simple dbDNA preparation technique was established through utilization of Phi29 DNA polymerase multiple displacement amplification,protelomerase TelN digestion and covalent ligation,as well as the subsequent removal of the back-bone loop through the action of a restriction enzyme and exonuclease.The efficiency of green fluorescent protein(GFP)was eval-uated following electroporation of the dbDNA-GFP vector and the pMax-dbDNA-GFP traditional plasmid vector into PB-MCs.The mRNA expression of interferon-γ(IFN-γ)in the two groups was quantified by qPCR.The dbDNA reprogramming vectors dbDNA-MOS,dbDNA-KLF4,dbDNA-MYC and dbDNA-BCL were prepared and subsequently transferred into PBMCs to induce reprogramming.The dbDNA-iPSC cell line was identified through morphological analysis,alkaline phosphatase stai-ning,RT-PCR,and detection of pluripotent stem cell markers.The ZFN and TALEN gene editing techniques were employed to insert an 11.5 kb ultra-long DNA fragment containing the Cas9 expression cassette,EGFP reading frame with stop codons in the sequence,a eukaryotic cell screening marker and other elements at the iPSC AAVS1.The identification of the iPSC lines with Cas9 integrated into AAVS1 was conducted through the utilization of red fluorescence detection,genomic PCR reaction and Western blot.The EGFP single-strand homologous repair template and EGFP sgRNA were co-transfected into positive iPSC cell lines to repair the erroneous stop codons in the EGFP gene and to express green fluorescent protein correctly.This approach was undertaken in order to verify the gene editing ability of the Cas9 protein.Results The dbDNA vector was successfully pre-pared and employed for gene expression.The GFP gene expression efficiency of dbDNA was similar to that of traditional plas-mid DNA.The expression level of IFN-γ mRNA in the dbDNA group was lower than that of traditional plasmid DNA group.The iPSC cell lines resembling human embryonic stem cells were successfully obtained,iPSC cell lines with positive alka-line phosphatase staining,pluripotency related gene expression and stem cell pluripotency markers.The ultra-long fragment CRISPR-Cas9 gene editing reporting system was successfully inserted into the safe harbor AAVS1 site of the cell line,and the integrated fragment was successfully inserted into the genome by genomic PCR.Red fluorescent protein was expressed.Cas9 protein expression and EGFP gene recovery was confirmed by Western blot.Green fluorescence was observed.Conclusion A simple technical procedure for the preparation of dbDNA is successfully established.The gene expression efficiency of the dbD-NA vector is comparable to that of traditional plasmid DNA,with less immune response.The dbDNA-derived iPSCs are success-fully obtained,which is confirmed by morphological analysis,alkaline phosphatase staining,RT-PCR,and stem cell pluripotency markers.An 11.5 kb ultra-long DNA fragment is successfully inserted into the iPSC AAVS1 safe harbor to establish a stable iPSC cell line with Cas9-mediated gene editing.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease and Parkinson's disease. Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.
Animals ; Mice ; Dysbiosis/metabolism* ; Mice, Knockout ; Humans ; Lysosomal Membrane Proteins/genetics* ; Receptors, Scavenger/genetics* ; Gastrointestinal Microbiome ; Myoclonic Epilepsies, Progressive/genetics* ; Vitamin E Deficiency/complications* ; Neurodegenerative Diseases/genetics* ; Bile Acids and Salts/metabolism* ; Male ; Lipid Metabolism ; Intestinal Mucosa/pathology*

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

Objective:To investigate the features of the brain structural network in patients with postpartum depression (PPD).Methods:This cross-sectional study included PPD patients who visited the mental health counseling clinic after delivery at the Jiangsu University Affiliated Yixing Hospital from June 2013 to September 2022 (PPD group). Matched non-PPD postpartum women based on age, years of education, and body mass index who came for postpartum follow-up (non-PPD postpartum group), and non-pregnant women who visited the hospital or underwent physical examinations during the same period (non-pregnant group) were also included. Demographic data and diffusion tensor imaging (DTI) data were collected for all three groups. The brain was partitioned into 90 regions using an anatomical template to construct the brain structural network. Network-based statistics (NBS) were applied to further screen and construct subnetworks. The efficacy of the subnetworks in identifying PPD was evaluated through multivariable logistics regression models and receiver operating characteristic curves. A comparison of the connectivity strength of white matter tracts and topological attributes of brain structural network parameters was conducted using independent samples t-tests, and the results were corrected using the false discovery rate (FDR) method. Results:(1) A total of 116 subjects were included, with 40 in the non-pregnant group, 40 in the non-PPD postpartum group, and 36 in the PPD group. PPD group had higher Edinburgh Postnatal Depression Scale (EPDS) scores than the non-pregnant and non-PPD postpartum groups [(18.0±4.1) scores vs. (2.5±1.2) and (6.1±2.1) scores, F=340.40; t=24.65,10.60 and 16.16 in pairwise comparison; all P<0.001]. (2) Compared to the non-pregnant group, there was a decrease in the connectivity strength of nine white matter tracts within the brain structural network of the postpartum group (including left dorsolateral superior frontal gyrus-left anterior cingulate and paracingulate gyrus, left dorsolateral superior frontal gyrus-right amygdala, left dorsolateral superior frontal gyrus-left insula, left insula-left lentiform nucleus, left insula-left hippocampus, left hippocampus-right amygdala, left hippocampus-left precuneus, left anterior cingulate and paracingulate gyrus-right amygdala, and right amygdala-right hippocampus) (all P<0.05, FDR corrected). No increased connection strengths were observed. There were no significant differences in the connection strengths of these nine tracts between the non-PPD and PPD groups. (3) A characteristic subnetwork for the maternal group was successfully constructed based on the nine tracts, which exhibited typical small-world properties (σ>1). Compared to the non-PPD maternal group, the characteristic path length in the PPD group was increased [(3.904±0.328) vs. (4.130±0.433), t=－2.58], and global efficiency was decreased [(0.361±0.036) vs. (0.331±0.053), t=2.91] (both P<0.05). Local property comparisons showed that the node efficiency values for the left dorsolateral superior frontal gyrus, left insula, left anterior cingulate and paracingulate gyrus, left hippocampus, right hippocampus, right amygdala, left precuneus and left putamen in the PPD group were significantly reduced [(0.273±0.023) vs. (0.267±0.030), t=0.98; (0.299±0.035) vs. (0.276±0.041), t=2.64; (0.265±0.019) vs. (0.258±0.025), t=1.38; (0.318±0.028) vs. (0.305±0.031), t=1.92; (0.312±0.027) vs. (0.302±0.031), t=1.50; (0.322±0.030) vs. (0.298±0.026), t=3.71; (0.356±0.040) vs. (0.338±0.056), t=1.62; (0.346±0.028) vs. (0.331±0.036), t=1.74; all P<0.05]. However, only the differences in node efficiency values for the left insula and right amygdala remained significant after FDR correction (corrected P=0.041 and 0.003). (4) Global efficiency, as well as node efficiency for the left insula and right amygdala, demonstrated good value for identifying PPD [areas under the curve (AUC) and their 95% CI were 0.827 (0.732-0.922), 0.741 (0.628-0.854), and 0.761 (0.653-0.867), respectively], with even better performance when combined [0.897 (0.828-0.969)]. (5) In the PPD group, global efficiency ( r=－0.43, P=0.008), node efficiency for the left insula ( r=－0.39, P=0.019), and node efficiency for the right amygdala ( r=－0.42, P=0.011) were all negatively correlated with EPDS scores. Conclusion:Aberrations in global efficiency, node efficiency for the left insula, and node efficiency for the right amygdala may serve as characteristic neuroimaging biomarkers for PPD.

As an excellent hosting matrices for enzyme immobilization, metal-organic framework (MOFs) provides superior physical and chemical protection for biocatalytic reactions. In recent years, the hierarchical porous metal-organic frameworks (HP-MOFs) have shown great potential in enzyme immobilization due to their flexible structural advantages. To date, a variety of HP-MOFs with intrinsic or defective porous have been developed for the immobilization of enzymes. The catalytic activity, stability and reusability of enzyme@HP-MOFs composites are significantly enhanced. This review systematically summarized the strategies for developing enzyme@HP-MOFs composites. In addition, the latest applications of enzyme@HP-MOFs composites in catalytic synthesis, biosensing and biomedicine were described. Moreover, the challenges and opportunities in this field were discussed and envisioned.
Metal-Organic Frameworks/chemistry* ; Porosity ; Enzymes, Immobilized/chemistry* ; Biocatalysis ; Catalysis