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.

Neuroendocrine neoplasms(NENs)are a rare group of tumors that originated from peptidergic neurons and neuroendocrine cells,which has neuroendocrine differentiation characteristics and expresses neuroendocrine markers.NENs occur in all parts of the body,especially in lung,gastrointestinal tract and pancreas.Both domestic and foreign researches showed that the incidence of NENs is on the rise.NENs have high heterogeneity and can originate in multiple tissues and organs,including pituitary,thyroid,parathyroid,skin,bronchial lung and thymus,gastrointestinal tract and pancreas,adrenal glands,genitourinary organs,etc.At the same time,when the classification and grading of NENs originating from the same tissue or organ are different,they also have significantly different biological behaviors.The high heterogeneity of NENs determines the difficulty and complexity of its diagnosis.In addition to clinical symptoms,it also needs to include special biomarkers,endoscopy,ultrasound,computed tomography(CT),magnetic resonance imaging(MRI)and various functional imaging methods for integrated diagnosis.In addition,the treatment of NENs also covers endoscopic therapy,surgical treatment,interventional therapy,drug therapy,radiotherapy and peptide receptor radionuclide therapy(PRRT).The development of treatment strategies requires not only following guidelines,but also making individual choices on the basis of multidisciplinary team(MDT)collaboration and integrated diagnosis and treatment.In 2024,the Society of Neuroendocrine Neoplasm of China Anti-Cancer Association once again organized experts in relevant fields to formulate the"China Anti-Cancer Association guideline for diagnosis and treatment of neuroendocrine neoplasms(2025 edition)"on the basis of the"China Anti-Cancer Association guideline for diagnosis and treatment of neuroendocrine neoplasm(2022 edition)",domestic and international guidelines and consensus,as well as the latest clinical research results.The guideline had been registered on Practice guideline REgistration for transPAREncy(PREPARE)with the registration number PREPARE-2024CN1158.The 2025 edition updated and revised the relevant content from the 2022 edition and further expanded recommendations beyond thoracic,gastrointestinal tract and pancreas NENs,including pituitary neuroendocrine tumors(PitNETs),medullary thyroid carcinoma(MTC),pheochromocytoma/paragangliomas(PPGLs)and Merkel cell carcinoma(MCC),with the expectation of providing references for clinical practitioners.

Objective To investigate the efficacy and safety of self-help inflatable balloon in the treatment of refractory benign upper digestive tract stricture.Methods From November 2022 to February 2024,10 patients with refractory benign upper digestive tract stricture underwent self-help inflatable balloon were retrospectively analyzed.Preoperative treatment,intraoperative and postoperative complications,dysphagia score before and after surgery,wearing time of external self-help inflatable balloon,and the clinical efficacy were evaluated.Results All the 10 patients received self-help inflatable balloon treatment.No complications such as bleeding and perforation occurred in all patients during the wearing of the balloon.The placement time of the balloon was 60～180 d,and the average wearing time was 104.9 d.Before surgery,nine cases had a stricture segment length less than 2 cm,and one case had a stricture segment length of 6 cm.The dysphagia score before surgery was(3.60±0.52),and the dysphagia score after removal of the self-help inflatable balloon was(0.60±0.52),and there was statistical significance in preoperative and postoperative comparison(P＜0.05).The dysphagia score 3 months after removal of the external self-help inflatable balloon was(0.70±0.48),there was no significant difference in dysphagia score between the day after surgery and 3 months after surgery(P＞0.05).The diameter of the stricture before and after operation was(5.09±2.02)mm and(10.35±0.73)mm respectively,and the difference was statistically significant(P＜0.05).Sore throat,wing of nose pain and balloon displacement were the most common adverse events,with 30.0％(3/10),50.0％(5/10)and 70.0％(7/10),respectively.Conclusion It is safe,effective and feasible to treat refractory benign upper digestive tract stricture with self-help inflatable balloon in vitro.It is worthy for clinical application.

Objective:To explore the clinical application value of artificial intelligence models in identifying bleeding events and hemorrhagic points during laparoscopic pancreatic surgery.Methods:This single-center retrospective cohort study collected surgical videos of 25 patients undergoing laparoscopic pancreatic surgery at the Department of General Surgery, Peking Union Medical College Hospital from January 2022 to December 2024. Videos within 5 seconds before and after representative bleeding events were captured at 30 frames/s, with 11 666 hemorrhagic-related video frames annotated. Two algorithm models were developed: a pigment-based model and a pigment+optical flow-based model for classification and target recognition of bleeding frames. The training and test sets for the pigment-based algorithm contained 4 692 hemorrhagic and 4 309 non-hemorrhagic frames, while those for the pigment+optical flow model included 1 339 hemorrhagic and 1 326 non-hemorrhagic frames. Performance evaluation was conducted using overlap thresholds, with accuracy and recall rates as key metrics.Results:The pigment-based model achieved 93.8% accuracy (134/143) and 43.3% recall (134/310) in hemorrhagic frame classification. At an overlap threshold of 0.3, the pigment-based model showed 84.1% accuracy (433/515) and 85.4% recall (433/507) in target recognition. When the threshold was increased to 0.5, the pigment+optical flow model demonstrated 88.1% accuracy (354/402) and 89.2% recall (354/397) in hemorrhagic target recognition.Conclusions:It is difficult to distinguish active bleeding from old bleeding completely by pigment information alone. The spatio-temporal features can be effectively extracted by combining pigment and optical flow information, and the bleeding can be accurately identified and located, which has potential clinical application value.

Objective To evaluate the accuracy of 6 commercial antibiotic susceptibility testing methods in detecting the sensitivity of carbapenems-resistant Klebsiella pneumoniae(CRKP)to tigecycline,and to provide an evidence for clinical laboratory to select the appropriate tigecyline susceptibility tests.Methods Non-duplicate CRKP clinically isolated from Aerospace Center Hospital from June 2023 to February 2024 were collected.60 cases of tigecycline intermediated CRKP[minimal inhibitery concentration(MIC)=4μg/ml]and 60 cases of drug-resistant CRKP(MIC≥8μg/ml)were screened by Vitek-2.The sensitivity of CRKP to tigecycline was detected by different methods.With the MIC test strip(MTS)as the reference method,the methodological evaluation of Vitek-2,commercial broth dilution method,E-test,Kirby-Bauer disk diffusion(KB)and disk combined with resensitization bufferwas carried out under the interpretation standards of the U S Food and Drug Administration(FDA)and the European Commission for Drug Susceptibility Testing(EUCAST),respectively.Results For the intermediate strains,under the FDA criteria,both the commercial broth dilution method and the disk combinedwith resensitization buffer method showed high consistency with the MTS method and were acceptable,whereas under the EUCAST criteria,all five methods were unacceptable.For the resistant strains,no matter what standard was,CA of all five methods were less than 90%,which were unacceptable.For all strains as a whole,the results were consistent with those of the resistant ones.Conclusion Under the current sample size,none of the five methods met the acceptable standards,especially not suitable for the recheck of strains with higher MICs.Commercial broth dilution method have the highest consistency with MTS,and it is worth expanding the sample size for further study.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

OBJECTIVE: To observe the efficacy and safety of Tiaowei Jiannao acupuncture (acupuncture for regulating defensive qi and nourishing brain) for post-ischemic stroke insomnia (PISI). METHODS: A total of 96 patients with PISI were randomized into an acupuncture group (32 cases, 1 case was excluded), a medication group (32 cases, 1 case dropped out, 1 case was excluded) and a sham-acupuncture group (32 cases, 1 case dropped out, 1 case was excluded). In the acupuncture group, Tiaowei Jiannao acupuncture was applied at bilateral Shenmai (BL62), Zhaohai (KI6), Hegu (LI4), Taichong (LR3), and Baihui (GV20), Sishencong (EX-HN1), Yintang (GV24⁺), Shenting (GV24), once a day, 1-day interval was taken after 6-day treatment, for 3 weeks totally. In the medication group, eszopiclone tablet was given orally, 1-3 mg a time, once a day for 3 weeks. In the sham-acupuncture group, non-invasive sham acupuncture was applied, the acupoint selection, frequency and course of treatment were the same as the acupuncture group. Before treatment, after 2,3 weeks of treatment, the scores of Pittsburgh sleep quality index (PSQI), self-rating sleep scale (SRSS), National Institutes of Health Stroke scale (NIHSS), Hamilton depression scale-17 (HAMD-17) were observed; before and after treatment, the sleep parameters were recorded using polysomnography (PSG); and the efficacy and safety were evaluated after treatment in the 3 groups. RESULTS: After 2,3 weeks of treatment, the scores of PSQI, HAMD-17 and SRSS in the acupuncture group and the medication group, as well as the SRSS scores in the sham-acupuncture group were decreased compared with those before treatment (P<0.05); after 2 weeks of treatment, the NIHSS score in the acupuncture group was decreased compared with that before treatment (P<0.05); after 3 weeks of treatment, the NIHSS scores in the acupuncture group, the medication group and the sham-acupuncture group were decreased compared with those before treatment (P<0.05). After 3 weeks of treatment, the scores of PSQI, SRSS, HAMD-17 and NIHSS in the acupuncture group and the medication group, as well as the NIHSS score in the sham-acupuncture group were decreased compared with those after 2 weeks of treatment (P<0.05). After 2,3 weeks of treatment, the scores of PSQI, SRSS and HAMD-17 in the acupuncture group and the medication group were lower than those in the sham-acupuncture group (P<0.05), the NIHSS scores in the acupuncture group were lower than those in the medication group and the sham-acupuncture group (P<0.05); after 3 weeks of treatment, HAMD-17 score in the acupuncture group was lower than that in the medication group (P<0.05), the NIHSS score in the medication group was lower than that in the sham-acupuncture group (P<0.05). Compared before treatment, after treatment, the total sleep time was prolonged (P<0.05), the wake after sleep onset, sleep latency, and non-rapid eye movement (NREM) sleep latency were shortened (P<0.05), the sleep efficiency was improved (P<0.05), the number of awakenings was reduced (P<0.05), the percentage of rapid eye movement (REM%) and the percentage of NREM stage 1 (N1%) were decreased (P<0.05), the percentage of NREM stage 2 (N2%) and the percentage of NREM stage 3 (N3%) were increased (P<0.05) in the acupuncture group and the medication group; the sleep latency was shortened in the sham-acupuncture group (P<0.05). After treatment, the PSG indexes in the acupuncture group and the medication group were superior to those in the sham-acupuncture group (P<0.05); in the acupuncture group, the number of awakenings was less than that in the medication group (P<0.05), the REM% and N1% were lower than those in the medication group (P<0.05), the N2% and N3% were higher than those in the medication group (P<0.05). The total effective rate were 93.5% (29/31) and 90.0% (27/30) in the acupuncture group and the medication group respectively, which were higher than 10.0% (3/30) in the sham-acupuncture group (P<0.05). There was no serious adverse events in any of the 3 groups. CONCLUSION Tiaowei Jiannao acupuncture improves the insomnia symptoms in patients with ischemic stroke, improves the quality of sleep, increases the deep sleep, promotes the recovery of neurological function, and relieves the depression. It is effective and safe for the treatment of PISI.
Humans ; Acupuncture Therapy ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Female ; Middle Aged ; Aged ; Acupuncture Points ; Treatment Outcome ; Adult ; Ischemic Stroke/complications* ; Stroke/complications* ; Sleep

BACKGROUND:Linagliptin exhibits the capacity to regulate macrophage polarization,shifting them from the pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This alteration results in a dampened release of inflammatory mediators,thereby mitigating local inflammation.OBJECTIVE:To explore the effects of linagliptin on macrophage polarization,osteoclast activation,and inflammatory osteolysis elicited by wear particles.METHODS:(1) Cell experiments:For macrophage polarization,RAW264.7 cells were cultured and divided into four groups:the control group received high-glucose culture medium;the M1-induced group received M1-inducing culture medium (high-glucose culture medium containing 100 ng/mL lipopolysaccharide and 20 ng/mL interferon-γ) to simulate an inflammatory environment;the low-and high-dose linagliptin groups were treated with 50 and 200 nmol/L linagliptin,respectively,for 4 hours before exposure to M1-inducing culture medium. After 24 hours of macrophage polarization induction,immunofluorescence staining and RT-PCR were performed. For osteoclast activation,RAW264.7 cells were cultured and divided into four groups:the control group was cultured with high-glucose culture medium,the osteoclast-induced group and low-and high-dose linagliptin groups were subjected to osteoclast induction. After osteoclast formation,cells were treated with linagliptin (50 and 200 nmol/L) for 3 days. Subsequently,cell tartrate-resistant acid phosphatase staining and RT-PCR were performed. (2) Animal experiments:Twenty-four male C57BL/6J mice were randomly divided into four groups:sham operation group,model group,low-dose linagliptin group,and high-dose linagliptin group. The model group,low-dose linagliptin group,and high-dose linagliptin group were induced to establish a cranial bone resorption model by injecting titanium particle suspension onto the surface of the skull. Starting from the 2nd day after modeling,the low-and high-dose linagliptin groups were orally administered linagliptin (2 and 10 mg/kg,respectively) once daily. After modeling for 3 weeks,serum macrophage polarization marker protein and inflammatory factor levels were detected;skull samples were collected for micro-CT scanning,bone parameter analysis,and hematoxylin-eosin staining to evaluate osteolysis and morphological changes.RESULTS AND CONCLUSION:(1) Cell experiments:Both low and high doses of linagliptin significantly suppressed M1 polarization while promoting M2 polarization compared to the M1-induced group (P<0.01). Notably,the high-dose group exhibited a more pronounced inhibitory effect (P<0.01). Inflammatory factor mRNA expression was elevated in the M1-induced group compared with the control group (P<0.01),whereas inflammatory factor mRNA expression was significantly lower in the low-and high-dose linagliptin groups compared with the M1-induced group (P<0.01). There was a significant upregulation of mRNA expression of osteoclast functional markers in the osteoclast-induced group compared with the control group (P<0.01). Conversely,both low and high doses of linagliptin led to a substantial downregulation of mRNA expression of these markers compared with the osteoclast-induced group (P<0.01),with the high-dose group exhibiting a more pronounced reduction. (2) Animal experiments:Titanium particle implantation induced cranial bone resorption damage in mice. Treatment with linagliptin effectively mitigated this bone resorption,with the high-dose group showing superior efficacy. To conclude,linagliptin has been shown to modulate macrophage polarization,inhibit osteoclast activation,and have a protective effect on the skeletal system.

Neuroendocrine neoplasms(NENs)are a rare group of tumors that originated from peptidergic neurons and neuroendocrine cells,which has neuroendocrine differentiation characteristics and expresses neuroendocrine markers.NENs occur in all parts of the body,especially in lung,gastrointestinal tract and pancreas.Both domestic and foreign researches showed that the incidence of NENs is on the rise.NENs have high heterogeneity and can originate in multiple tissues and organs,including pituitary,thyroid,parathyroid,skin,bronchial lung and thymus,gastrointestinal tract and pancreas,adrenal glands,genitourinary organs,etc.At the same time,when the classification and grading of NENs originating from the same tissue or organ are different,they also have significantly different biological behaviors.The high heterogeneity of NENs determines the difficulty and complexity of its diagnosis.In addition to clinical symptoms,it also needs to include special biomarkers,endoscopy,ultrasound,computed tomography(CT),magnetic resonance imaging(MRI)and various functional imaging methods for integrated diagnosis.In addition,the treatment of NENs also covers endoscopic therapy,surgical treatment,interventional therapy,drug therapy,radiotherapy and peptide receptor radionuclide therapy(PRRT).The development of treatment strategies requires not only following guidelines,but also making individual choices on the basis of multidisciplinary team(MDT)collaboration and integrated diagnosis and treatment.In 2024,the Society of Neuroendocrine Neoplasm of China Anti-Cancer Association once again organized experts in relevant fields to formulate the"China Anti-Cancer Association guideline for diagnosis and treatment of neuroendocrine neoplasms(2025 edition)"on the basis of the"China Anti-Cancer Association guideline for diagnosis and treatment of neuroendocrine neoplasm(2022 edition)",domestic and international guidelines and consensus,as well as the latest clinical research results.The guideline had been registered on Practice guideline REgistration for transPAREncy(PREPARE)with the registration number PREPARE-2024CN1158.The 2025 edition updated and revised the relevant content from the 2022 edition and further expanded recommendations beyond thoracic,gastrointestinal tract and pancreas NENs,including pituitary neuroendocrine tumors(PitNETs),medullary thyroid carcinoma(MTC),pheochromocytoma/paragangliomas(PPGLs)and Merkel cell carcinoma(MCC),with the expectation of providing references for clinical practitioners.