Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective:To explore the effect of accurately localized mini anterolateral thigh perforator flap in repairing medium-sized skin and soft tissue defects in fingers.Methods:The study was a retrospective observational study. From December 2019 to September 2022, 15 patients with medium-sized skin and soft tissue defects who met the inclusion criteria in fingers were admitted to the Second Affiliated Hospital of Wenzhou Medical University, including 12 males and 3 females, aged 23 to 62 years. After debridement, the wounds were all accompanied by exposed tendons, bones, vessels and nerves, with an area from 4.0 cm×3.0 cm to 8.0 cm×3.5 cm. Computed tomography angiography and color Doppler ultrasonography examinations were performed on both lower limbs of the patient before surgery to accurately locate the anterolateral thigh perforators. When the flap with area from 6.0 cm×3.0 cm to 11.0 cm×4.0 cm was harvested, the flap was thinned. The artery and vein perforators of the flap were anastomosed respectively with the digital artery and dorsal metacarpal vein. If there was avulsion injury, infection, or burn in the recipient area, the main arterial and veinous vessels carried by the skin flap was anastomosed with the radial artery and accompanying vein. The lateral thigh cutaneous nerve carried by the flap was anastomosed with the stump of the digital nerve. The types of perforators of the lateral thigh artery were observed during operation and compared with the location of the vessels before operation. After operation, the survival and adverse complication of the flap were closely observed. During follow-up, the skin flap color, texture, and shape were observed; the wound healing in donor area was observed. At the last follow-up, the two-point discriminative distance of the affected finger pulp was measured, and the function of the affected finger was evaluated using the trial standard for the evaluation of functions of upper limbs of Hand Surgery Society of Chinese Medical Association, and the interphalangeal joint movement of the affected finger was observed; the patients' complaints about the adverse effects of flap resection on lower limbs were recorded.Results:During the operation, it was observed that the perforators of the flaps in 11 patients were the descending branch of the lateral circumflex thigh artery, in two patients, the perforators of skin flaps were the oblique branch of the lateral thigh artery, and the perforators in another two patients were the transverse branch of the lateral circumflex thigh artery, which were consistent with the preoperative vascular localization. After operation, all flaps survived without vascular crisis and infection. The patients were followed up for 6-12 months, the flaps had excellent color, texture, and appearance; only linear scars remained on the donor wound. At the last follow-up, the two-point discrimination distance in the finger pulp was 7-11 mm; the affected finger function was rated as excellent in 6 cases, good in 6 cases, and fair in 3 cases; the flexion and extension function of the finger was not affected; two patients complained of numbness in the lateral thigh after excision of the skin flap, and the other 13 patients had no complain of adverse complaints.Conclusions:The perforating branch in lateral thigh region can be accurately located by computed tomography angiography and color Doppler ultrasonography, accurate positioning of perforators before operation can reduce the damage to the donor area during the incision of the flap, the appearance and function of the affected finger can be restored to the maximum extent by thinning the transplanted flap and rebuilding the finger sensation. Therefore, it is an effective and reliable way to repair the medium-sized skin and soft tissue defects of fingers with the mini thigh anterolateral perforator flap.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

OBJECTIVE To investigate the effects of total glucosides of paeony （TGP） on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside （TWP） in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2，4-dinitrofluorobenzene-acetone olive oil solution （volume ratio was 4∶1） on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group， loratadine group （0.9 mg/kg）， TWP group （9.45 mg/kg）， TGP group （162 mg/kg） and compatibility group （TWP 9.45 mg/kg+TGP 162 mg/kg）， with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization， administration groups were given relevant medicine intragastrically， and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically， once a day， for consecutive 21 d. Twenty-four hours later after the final administration， the general condition of rats in each group was observed， and the eczema area and severity index （EASI） were scored； ear swelling degree of rats was measured， and the skinhistomorphology observation and pathological score were performed； protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase （p38 MAPK）， phosphorylated p38 MAPK （p- MAPK） and phosphorylation level of p38 MAPK in rat skin tissue were detected； the levels of inflammatory indexes （interleukin-4， interferon- γ）， liver and kidney function indexes [glutamic-pyruvic transaminase （GPT）， glutamic-oxaloacetic transaminase （GOT）， serum creatinine （SCr） and blood urea nitrogen （BUN）] and oxidant stress indexes [total superoxide dismutase （T-SOD） and malondialdehyde （MDA）] were measured. RESULTS Compared with normal group， EASI score， ear swelling degree， pathological score， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation level of p38 MAPK， the levels of inflammatory indexes and BUN were all increased significantly in model group （P＜0.05）. Compared with model group， EASI scores， ear swelling degree， pathological scores， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups （P＜0.05）. The levels of GPT， GOT， SCr and BUN were increased significantly in TWP group， while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly （P＜0.05）. The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group， while the levels of MDA were increased significantly （P＜0.05）. The compatibility group showed more obvious effect in improving the ear swelling degree， pathological score， p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes， and could reverse the abnormality of liver and kidney indexes caused by TWP （P＜0.05）. CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory， synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.

Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury.The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gammainducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.

Objective:To introduce a surgical method and clinical effect of using Masquelet technique combined with skin graft to cover chronic refractory wounds in elderly patients.Methods:From September 2020 to September 2022, 20 elderly patients with wounds of bone or tendon exposure in lower limbs were treated in the Department of Wound Repair, the Second Affiliated Hospital of Wenzhou Medical University. Due to the age and poor general condition of the patients, flap transfer for wound coverage were not allowed. Masquelet technique was therefore applied in the treatment of chronic wounds of such patients. Sizes of wounds were found at 4.5 cm×3.0 cm to 15.0 cm×6.0 cm and all accompanied with tendon and bone exposure, after thorough debridement. Wounds were then sealed with antibiotic bone cement several times. After having induced formation of membrane in wounds, free mesh skin graft was used to cover the refractory wounds. The patients were entered in follow up regularly after surgery at outpatient service, and telephone or video reviews. The wound healing of patients and whether there were related complications in the skin donor area were observed. The number of operation times in the first stage was 1-4 with an average of 1.3 times ± 0.7 times. Lower Extremity Function Scale (LEFS) was used to evaluate the recovery of lower limb function.Results:All 20 wounds healed well. The follow-up time was 3-12 months, with an average of 7.6 months. The appearance and texture of the skin in the wounds area were satisfactory. The mean LEFS was 69.83 point ± 10.82 point.Conclusion:Using Masquelet technique combined with free skin grafting to treat refractory wounds in the elderly patients can achieve satisfactory clinical outcomes. It is a simple and reliable supplement to the wound repair, and can reduce the surgical risk.

AIM:To explore the impact of Delta-like ligand 3(DLL3)on the progression of prostate cancer(Pca)and to elucidate its potential molecular mechanisms.METHODS:Overexpression and interference plasmids of DLL3 gene were constructed,and the effects of DLL3 on the proliferation,migration and invasion of Pca cells were as-sessed.Tumorigenesis assay was employed to determine whether DLL3 influenced the proliferation of PC-3 cells in vivo.The impact of DLL3 on epithelial-mesenchymal transition(EMT)and mitogen-activated protein kinase(MAPK)signaling was investigated through Western blotting.RESULTS:Overexpression of DLL3 significantly enhanced the proliferation,migration,invasion and EMT processes of Pca cells compared with empty vector group and blank control group(P＜0.05).Conversely,knockdown of DLL3 expression yielded opposite effects(P＜0.05).Moreover,up-regulation of DLL3 promoted tumor growth in the nude mouse xenograft model(P＜0.05).Further investigation demonstrated that DLL3 up-regulation led to increases in the levels of MAPK signaling pathway-related proteins.Interestingly,MAPK inhibitor effec-tively reduced the proliferation,migration and invasion of Pca cells caused by DLL3 overexpression(P＜0.05).CON-CLUSION:DLL3 promotes the proliferation,migration and invasion of Pca through the MAPK pathway.