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

Objective:To explore the biomarkers associated with multiple myeloma in remission phase (MM-RP) in order to provide potential indicators for disease monitoring and prognostic evaluation.Methods:Bone marrow blood samples were prospectively collected from 9 newly diagnosed multiple myeloma (NDMM) patients and 9 MM-RP patients in Beijing Chaoyang Hospital of Capital Medical University from January to October 2020. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for proteomic analysis in 3 independent experiments, each containing 3 paired NDMM and MM-RP samples. Differentially expressed proteins (DEP) consistently identified across all 3 experiments were considered potential MM-RP biomarkers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for enrichment analyses of the biological functions of these potential biomarkers. Protein-protein interaction (PPI) networks were constructed using the STRING 11.5 database, and α-2-macroglobulin (α2M) was identified as a hub protein. The UCSC Xena database was utilized, and the overall survival (OS) of MM patients with high or low α2M expression [stratified by the average level of α2M transcriptome sequencing (RNA-seq) data] was analyzed by using Kaplan-Meier. A multivariate Cox proportional hazards model adjusted for age, International Staging System (ISS) stage and treatment regimen was employed to analyze the impact of α2M expression on OS of MM patients. The Human Protein Atlas (HPA) database was used to examine α2M mRNA expression patterns in 33 cancer types. The correlation of drug sensitivity [50% inhibiting concentration ( IC50)] with α2M expression was assessed using pharmacogenomic data from the GSCALite platform. Results:Among 104 proteins consistently identified in 3 proteomic experiments, 34 DEP were found between NDMM and MM-RP (∣fold change∣>1.0 and P < 0.05), including 25 upregulated DEP and 9 downregulated DEP in MM-RP. GO analysis showed that the identified MM-RP potential markers were mainly involved in biological processes such as complement activation and humoral immune response, and the molecular functions mainly involved serine hydrolase activity, serine peptidase activity, etc., and were mainly distributed in secretory granules, blood particles, and other parts; KEGG enrichment analysis showed that biomarkers were mainly enriched in the complement and coagulation cascade pathways. In the human α2M PPI network constructed using data from the STRING database, there were 10 proteins that interacted with α2M, with a connectivity of 7.82, and had direct interactions with 71% of the proteins in the network, the betweenness centrality value was 0.06, and the closeness centrality value was 1, indicating significant network centrality feature of α2M. In the constructed PPI network of α2M protein and DEP screened by proteomics, there were interactions between α2M protein and 11 MM-RP markers screened by proteomics, and the betweenness centrality value of α2M reached 0.50, the closeness centrality value was 0.67, indicating that α2M was at the core position of the PPI network. UCSC Xena analysis revealed that MM patients with low α2M expression (523 cases) had worse OS than those with high expression (336 cases) ( P =0.024). Multivariate Cox regression analysis confirmed that low α2M expression was an independent risk factor for poor OS (compared with high α2M expression: HR = 0.726, 95% CI: 0.550-0.960, P = 0.024). HPA database analysis demonstrated that the α2M expression levels were variable in different types of cancer, its level in glioblastoma multiforme, clear cell renal cell carcinoma, and stomach adenocarcinoma was higher than that in normal tissues (all P < 0.05), and its level in urothelial carcinoma, breast cancer and cervical squamous cell carcinoma was lower than that in normal tissues (all P < 0.05). GSCALite analysis revealed negative correlations between α2M expression level and IC50 values of B-Raf kinase inhibitors, B-Raf V600E inhibitors and dabrafenib mesylate. Conclusions:α2M expression level in MM-RP patients is lower than that in NDMM patients, and its expression level may be related to the prognosis of patients, which is expected to become a novel biomarker reflecting the disease activity of MM.

Objective To investigate the therapeutic mechanism of Shen Wu Yizhi Capsule in the treatment of post-stroke cognitive impairment(PSCI)by using network pharmacology methods and clinical trial validation.Methods A prospective trial was carried out in 90 cases of patients with PSCI admitted to Taihe Traditional Chinese Medicine Hospital Affiliated to Anhui University of Chinese Medicine from August 2022 to February 2024.The patients were randomly divided into the control group and the trial group by random number table method,with 45 cases in each group.The control group was treated with conventional treatment for PSCI,and the trial group was treated with Shen Wu Yizhi Capsule orally on the basis of treatment for the control group.The treatment course for the two groups covered 28 days.The changes of Mini-Mental State Examination(MMSE)score,Montreal Cognitive Assessment(MoCA)score,and the serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in the patients of the two groups were observed before and after treatment.Moreover,the incidences of adverse events in the two groups were recorded,thus to evaluate the safety of the treatment regimens in the two groups.And then the network pharmacological research was performed.TCMSP and literature review were used to obtain the active ingredients of Shen Wu Yizhi Capsule,GeneCards and other databases were used to obtain the PSCI disease targets,and the common targets were inputted into the STRING database to construct the PPI network.Cytoscape 3.9.0 was used to construct the network diagram of Shen Wu Yizhi Capsule-PSCI-targets,DAVID was used to perform GO and KEGG pathway enrichment analysis,and then molecular docking was used to verify the binding activity.Results(1)The results of clinical trial showed that after 28 days of treatment,the MMSE and MoCA scores of patients in the two groups were increased compared with those before treatment(P<0.05),and the increase of the scores in the trial group was significantly superior to that in the control group(P<0.05).The serum levels of TNF-α and IL-6 were decreased compared with those before treatment(P<0.05),and the decrease in the trial group was significantly superior to that in the control group(P<0.05).During the trial,both groups of patients did not show obvious adverse reactions,with high safety.(2)The network pharmacological research of Shen Wu Yizhi Capsule yielded 92 active ingredients,803 targets,5 209 disease targets and 556 intersection targets.The core targets were AKT1,TNF,IL-6,TP53 and IL-1B,and the key compounds were deoxyharringtonine,senkyunone and genkwanin.The GO enrichment analysis obtained 1 812 GO entries,of which 154 entries were related with cellular component(CC),1 332 entries were related with biological process(BP),and 326 entries were related with molecular function(MF).The KEGG pathway enrichment analysis yielded 195 signaling pathways.The molecular docking results showed that the key compounds of Shen Wu Yizhi Capsule had good binding activities with the core targets.Conclusion The clinical efficacy of Shen Wu Yizhi Capsule in the treatment of PSCI is remarkable,and its therapeutic mechanism is probably related with multiple components through the signaling pathways such as AKT1,TNF,and IL-6.The results will provide reference for the in-depth study of Shen Wu Yizhi Capsule.

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

Objective:To investigate the efficacy and safety of flumatinib in the treatment of imatinib-resistant or imatinib-intolerant patients with chronic phase chronic myelogenous leukemia (CML-CP).Methods:The clinical data of 9 CML-CP patients who received flumatinib after imatinib resistance or intolerance in Jining No. 1 People's Hospital from April 2020 to May 2021 were retrospectively analyzed. Patients were evaluated for the hematologic, cytogenetic and molecular responses, progression-free survival (PFS), event-free survival (EFS), and adverse reactions.Results:Among 9 CML-CP patients, there were 4 imatinib-resistant patients and 5 imatinib-intolerant patients. The median duration of flumatinib exposure was 17 months (1-25 months). Except for 1 case who discontinued flumatinib early due to grade 4 thrombocytopenia and other adverse reactions, 7 of the remaining 8 cases achieved the best response at 3, 6 and 12 months of flumatinib therapy. By the end of follow-up in April 2022, 7, 7 and 6 patients achieved complete cytogenetic response (CCyR), major molecular response (MMR) and molecular response 4.5 (MR4.5), respectively. The median time to achieving CCyR, MMR and MR4.5 was 4.5 months (3-6 months), 12 months (3-12 months) and 15 months (3-21 months), respectively. Within 17 months (11-25 months) of follow-up, 7 of the 9 patients had EFS and 8 patients with continuous flumatinib had PFS. Among 9 patients treated with flumatinib, hematologic adverse reactions were observed in 6 cases, and grade 3-4 hematologic adverse reactions occurred in 2 cases. Non-hematologic reactions events mainly included diarrhea (4 cases), muscle ache (2 cases), fatigue (2 cases) and liver damage (2 cases), which were all grade 1-2.Conclusions:Flumatinib is effective and well tolerated in the treatment of imatinib-resistant or imatinib-intolerant CML-CP patients.

Objective:To investigate the clinical efficacy of qualitative and staging diagnosis of rectal tumors with dual contrast-enhanced ultrasonography and interventional biopsy.Methods:A total of 300 patients with rectal tumors who received treatment in The First People's Hospital of Huzhou from December 2019 to March 2022 were included in this study. All patients underwent dual contrast-enhanced ultrasonography and interventional biopsy followed by focus resection. Taking the postoperative histopathological test results as the gold standard, the efficacy of dual contrast-enhanced ultrasonography and interventional biopsy in the localization, qualitative analysis, and staging of rectal tumors was analyzed.Results:The compliance rate of dual contrast-enhanced ultrasonography and interventional biopsy in the localization of rectal tumors was 100%. The sensitivity, specificity, and accuracy of the dual contrast-enhanced ultrasonography and interventional biopsy for qualitative diagnosis of rectal tumors were 94.8%, 97.8%, and 96.7%, respectively. The Kappa value used for assessing agreement in the qualitative diagnosis of rectal tumors between dual contrast-enhanced ultrasonography and interventional biopsy and postoperative tissue pathological examination results was 0.947. The area under the curve plotted for qualitative diagnosis of rectal tumors was 0.974. The sensitivity, specificity, and sensitivity of dual contrast-enhanced ultrasonography and interventional biopsy for diagnosis of stage I-III rectal cancer were 94.1%-97.8%. The Kappa values used for assessing agreement in staging diagnosis of stage I-III rectal cancer between dual contrast-enhanced ultrasonography and interventional biopsy and postoperative tissue pathological examination results were 0.923, 0.912, and 0.927, respectively. The areas under the curve plotted for staging diagnosis of rectal cancer were 0.961, 0.955, and 0.970, respectively.Conclusion:Dual contrast-enhanced ultrasonography and interventional biopsy have a high efficacy in the localization, qualitative diagnosis, and staging diagnosis of rectal tumors.

Objective:To summarize the clinical characteristics and efficacy of hemorrhage resulted from cortical venous infarction with seizure as the first symptom after craniotomy.Methods:Eleven patients with hemorrhage resulted from cortical venous infarction with seizure as the first symptom after craniotomy admitted to Neurosurgical Center, 988 th Hospital of PLA Joint Logistic Support Force from June 2011 to September 2019 were chosen in our study; primary diseases included meningioma in 7 patients, contusion and laceration of frontal lobe in 2, hypertensive cerebral hemorrhage in 1, and obsessive-compulsive disorder in 1 patient. Epilepsy was the first symptom after craniotomy. Clinical characteristics and efficacy of these patients were analyzed retrospectively; seizure control efficacy was evaluated by Engel grading. Results:First seizure occurred 4 h-7 d after craniotomy in these 11 patients, including 2 with focal sensory retention seizure, 3 with focal bilateral tonic-clonic seizure, and 6 with general tonic-clonic seizure. Follow-up cranial CT revealed hematoma in surgical region, adjacent cortex or subcortex in 9 patients (hematoma volume: 15-50 mL); emergency craniotomy (hematoma clearance) and decompressive craniectomy was performed in 5 patients; only emergency craniotomy (hematoma clearance) was performed in 3 patients; conservative treatment was performed in 1 patient. A small amount of diffuse bleeding with severe cerebral edema in the surgical region appeared in 2 patients, and the transient limb paralysis gradually recovered after 2 months of conservative treatment. Follow-up was performed for (4.5±1.7) years ([2.3-7.0] years). During the last follow-up, 4 patients were normal, 5 patients had mild to moderate hemiplegia, 1 had mild decreased vision in the right eye, and 1 had long-term coma. Epileptic control efficacy analysis indicated that 8 had Engel grading I and 3 grading II.Conclusion:Complete removal of hematoma and inactivated brain tissues can effectively control seizures and rebleeding in patients with hemorrhage resulted from cortical venous infarction.

Methanol has become an attractive substrate for the biomanufacturing industry due to its abundant supply and low cost. The biotransformation of methanol to value-added chemicals using microbial cell factories has the advantages of green process, mild conditions and diversified products. These advantages may expand the product chain based on methanol and alleviate the current problem of biomanufacturing, which is competing with people for food. Elucidating the pathways involving methanol oxidation, formaldehyde assimilation and dissimilation in different natural methylotrophs is essential for subsequent genetic engineering modification, and is more conducive to the construction of novel non-natural methylotrophs. This review discusses the current status of research on methanol metabolic pathways in methylotrophs, and presents recent advances and challenges in natural and synthetic methylotrophs and their applications in methanol bioconversion.
Humans ; Methanol/metabolism* ; Metabolic Engineering ; Metabolic Networks and Pathways ; Biotransformation

Objective:To evaluate the effect of electroacupuncture (EA) on Golgi apparatus stress in the rats with endotoxin-induced acute lung injury (ALI).Methods:Twenty clean-grade male Sprague-Dawley rats, aged 2 months, weighing 160-185 g, were divided into 4 groups ( n=5 each) according to a random number table method: control group (C group), endotoxin group (LPS group), EA plus endotoxin group (EA+ LPS group), and sham EA plus endotoxin group (SEA+ LPS group).The model of endotoxin-induced ALI was developed by intravenous injection of lipopolysaccharide (LPS) 5 mg/kg in anesthetized animals.Bilateral Zusanli (ST36) and Neiguan (PC6) acupoints were stimulated with an electric stimulator for 30 min once a day at 1-4 days before and during model preparation in group EA+ LPS.In group SEA+ LPS, acupuncture needles were inserted to the surface of ST36 and PC6 acupoints with no current stimulation, and the other parameters were the same as those previously described in group EA+ LPS.Blood samples were collected from the abdominal aorta at 6 h after development of the model for measurement of concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum by enzyme-linked immunosorbent assay.The animals were sacrificed and lungs were removed for microscopic examination of the pathological changes of lung tissues (with a light microscope) and morphological changes of Golgi apparatus (with a transmission electron microscope) and for determination of wet to dry lung weight (W/D) ratio, cell apoptosis index (by TUNEL), activity of superoxide dismutase (SOD) (by WST-1 method), content of malondialdehyde (MDA) (by TBA method), and expression of Golgi matrix protein 130 (GM130), Golgin-84 and Golgi phosphoprotein 3 (GOLPH3) protein and mRNA in lung tissues (by Western blot or real-time polymerase chain reaction). Results:Compared with group C, the lung injury score, W/D ratio, cell apoptosis index, serum IL-6 and TNF-α concentrations and MDA content were significantly increased, SOD activity was decreased, the expression of GM130 and Golgin-84 protein and mRNA was down-regulated, the expression of GOLPH3 protein and mRNA was up-regulated ( P<0.05), and Golgi apparatus was swollen and vacuolated in the other three groups.Compared with group LPS, lung injury score, W/D ratio, cell apoptosis index, serum IL-6 and TNF-α concentrations and MDA content were significantly decreased, SOD activity was increased, the expression of GM130 and Golgin-84 protein and mRNA was up-regulated, the expression of GOLPH3 protein and mRNA was down-regulated ( P<0.05), and swelling and vacuolization of Golgi apparatus were reduced in group EA+ LPS, and no significant change was found in the parameters mentioned above in group SEA+ LPS ( P>0.05). Conclusions:The mechanism by which EA reduces endotoxin-induced ALI may be related to inhibition of Golgi apparatus stress in lung tissues of rats.