ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective:To develop a deep learning-based segmentation model MT-UNet to automatically segment bone metastases and benign bone lesions in bone scintigraphy with SPECT/CT.Methods:A total of 93 patients (48 males and 45 females, age 28-84 years) who underwent bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from June 2023 to December 2023 were enrolled retrospectively in this study, with a total of 184 bone lesions (94 benign lesions and 90 metastatic tumors). The MT-UNet was employed to segment bone lesions in SPECT, CT and SPECT/CT images respectively. Comparative analysis with 8 segmentation models was performed. The training set and validation set were divided by using 5-fold cross-validation and transfer learning was introduced to further enhance the robustness of the model. An additional cohort of 22 patients (15 males and 7 females, age 37-87 years) who received bone SPECT/CT in the Department of Nuclear Medicine, General Hospital of Northern Theater Command from April 2023 to May 2023 were included, comprising 40 bone lesions (22 benign lesions and 18 metastatic tumors) as the test set of MT-UNet. Segmentation performance of different models was assessed using accuracy, sensitivity, specificity, AUC, intersection over union and Dice similarity coefficient (DSC). Delong test was used to compare the segmentation efficacy among different models in the test set.Results:In the validation set, MT-UNet demonstrated DSC of 0.940, 0.962, and 0.963 for SPECT, CT, and SPECT/CT bone lesion segmentation, respectively, which were outperformed other models. Following transfer learning implementation, the SPECT/CT model′s DSC was improved to 0.984. In the test set, MT-UNet maintained comparable segmentation performance to the validation set, with significant AUC differences among the three models ( Z values: from -15.42 to -9.27, all P<0.01). Compared with conventional image interpretation, MT-UNet-based segmentation reduced physician interpretation time from 164min to 102min. Conclusion:MT-UNet has shown good performance in automatic segmentation of bone metastases and benign bone lesions, and is expected to become an important part of SPECT/CT image intelligent diagnosis system for bone metastases.

Objective To investigate the efficacy of Yiqi Wenyang Sanjie Decoction in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution,and to observe its effect on serum inflammatory factors and immune function.Methods From January 2020 to June 2024,a total of 106 patients with pulmonary ground glass nodules and yang-deficiency constitution admitted to the Department of Respiratory Medicine and Preventive Treatment of Disease Center of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine were selected.The patients were randomly divided into control group and Chinese medicine group by random number table method,with 53 cases in each group.The patients in the control group were only given follow-up without any intervention,and the patients in the Chinese medicine group were treated with Yiqi Wenyang Sanjie Decoction for 3 months.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,maximum diameter of pulmonary ground glass nodules,serum levels of inflammatory factors of interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α),and levels of immune function indicators of peripheral blood CD3+,CD4+cell percentage and CD4+/CD8+ratio.After treatment,the efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the control group and 3 cases fell off from the Chinese medicine group.A total of 98 cases were eventually included,and 48 cases were in the control group and 50 cases were in the Chinese medicine group.(2)After 3 months of treatment,the total effective rate of the Chinese medicine group was 46.00%(23/50),and that of the control group was 10.42%(5/48).The intergroup comparison(tested by chi-square test)showed that the efficacy of the Chinese medicine group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group were lowered(P＜0.05),while the TCM syndrome score and the maximum diameter showed no obvious changes compared with those at enrollment(P＞0.05);the intergroup comparison showed that the reduction of TCM syndrome score and the maximum diameter of pulmonary ground glass nodules in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the levels of serum inflammatory factors of IL-6,IL-17A and TNF-α in the Chinese medicine group were significantly lowered compared with those at enrollment(P＜0.05),while there was no significant change in serum IL-6,IL-17A and TNF-α levels of the control group(P＞0.05);the intergroup comparison showed that the decrease of serum IL-6,IL-17A and TNF-α levels in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(5)After treatment,the percentage of T lymphocyte subset CD4+and the ratio of CD4+/CD8+in the Chinese medicine group were significantly increased compared with those at enrollment(P＜0.05),while there was no significant change in the percentage of CD3+,CD4+cells and the ratio of CD4+/CD8+of the control group and in the percentage of CD3+cells of the Chinese medicine group(P＞0.05).The intergroup comparison showed that the increase of CD4+percentage and CD4+/CD8+ratio in the Chinese medicine group was significantly superior to that in the control group(P＜0.05).(6)There were no obvious adverse reactions occurring in the Chinese medicine group during the treatment,showing relatively high safety.Conclusion Yiqi Wenyang Sanjie Decoction exerts certain effect in the treatment of patients with pulmonary ground glass nodules and yang-deficiency constitution.It can effectively promote the reduction of nodules,relieve clinical symptoms,decrease serum levels of inflammatory factors,improve immune function,and has good safety.

Objective To investigate the potential role of plasma adiponectin concentration in predicting the response of patients with depression to electroconvulsive therapy(ECT).Methods This study enrolled depressive patients scheduled for ECT at the First Hospital of Shanxi Medical University between January 2022 and March 2024.Patients were categorized as either ECT responders(>50%reduction)or non-responders(≤50%reduction)based on post-ECT reduction rate of the 24-item Hamilton depression scale(HAMD)scores from baseline.Plasma adiponectin levels were measured in all patients before their first ECT treatment.To identify predictors of ECT response in patients with depression,the predictive value of plasma adiponectin was evaluated using receiver operating characteristic(ROC)curve analysis.Results A total of 80 patients with depression were enrolled including 44 in the ECT-responsive group and 36 in the non-responsive group.The plasma adiponectin level was significantly higher in the responsive group than in the non-responsive group[5.67(3.64,10.55)μg/mL vs.4.01(2.59,5.04)μg/mL,P=0.002].Pearson correlation analysis revealed a significant positive correlation between plasma adiponectin levels and the HAMD reduction rate(r=0.300,P=0.007).Multivariate logistic regression analysis showed that plasma adiponectin was independently associated with the response to ECT in patients with depression(OR=1.218,95%CI:1.009-1.470,P=0.040).Furthermore,ROC curve analysis demonstrated that the area under the curve(AUC)for adiponectin in predicting ECT response was 0.748(95%CI:0.583-0.813).Conclusion Pretreatment plasma adiponectin may serve as a potential biomarker for predicting response to ECT in patients with depression.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.

Noggin is a protein secreted by human cells and belongs to the bone morphogenetic protein (BMP) family, which can inhibit the formation and proliferation of bone tissue. The initial research found that Noggin is mainly involved in the development of the embryonic skeletal and nervous systems in vertebrate embryos. Subsequent studies have found that Noggin also plays an important role in bone metabolism and bone mineral density regulation in adults, mainly by regulating the activities of signaling pathways such as Wnt/β-catenin, notch and hedgehog. Meanwhile, there is also a certain mutual influence among various channels. This article mainly reviews the relevant research on the regulation of osteoporosis by Noggin in signaling pathways, clarifies the related mechanism of Noggin in various signaling pathways, and analyzes the current research status and prospects of Noggin.

Objective:To investigate the therapeutic efficacy and safety of tislelizumab combined with platinum-based drugs in patients with advanced non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Eighty-six patients with clinical stage Ⅳ NSCLC in Huaibei People's Hospital from June 2020 to June 2023 were selected as the study subjects, and the patients were divided into the control group and the observation group based on the randomized numerical table method, with 43 cases in each group. The control group was treated with platinum-based drugs, the observation group was treated with platinum-based drugs combined with tislelizumab, and all patients were treated for 4-6 cycles. The two groups were compared in terms of therapeutic efficacy, serum tumor markers [carcinoembryonic antigen (CEA), cytokeratin 19 soluble fragment (CYFRA21-1) and carbohydrate antigen 125 (CA125)] detected by chemiluminescence method, serum immune function indicators [CD3 +, CD4 +, CD8 + cell ratios and CD4 + cell number-to-CD8 + cell number ratio (CD4 +/CD8 +)] detected by flow cytometry, and quality of life [European Organization for Research and Treatment of Cancer (EORTC) quality of life measurement scale (QLQ-C30) scores in functional domain and symptom domain], and incidence of adverse reactions. Results:The differences in baseline data of age, gender, degree of tumor differentiation, pathological type, lesion location, programmed death receptor ligand 1 expression between the observation group and the control group were not statistically significant (all P > 0.05). After treatment, the objective remission rates in the observation and control groups were 34.9% (15/43) and 18.6% (8/43), respectively, and the difference was not statistically significant ( χ2 = 2.91, P = 0.088); the disease control rate in the observation group was 74.4% (32/43), which was higher than that in the control group [51.2% (22/43)], and the difference was statistically significant ( χ2 = 4.98, P = 0.026). The differences in the serum levels of CEA, CYFRA21-1 and CA125 between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the serum levels of CEA, CYFRA21-1 and CA125 in the observation group were lower than those in the control group after treatment, and the differences were all statistically significant (all P < 0.01). The differences in the CD3 +, CD4 +, CD8 + cell ratios and CD4 +/CD8 + between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the CD3 +, CD4 + cell ratios and CD4 +/CD8 + in the observation group were higher than those in the control group, the CD8 + cell ratio was lower than that in the control group after treatment, and the differences were all statistically significant (all P < 0.01). Before treatment, there were no statistically significant differences in the scores of EORTC QLQ-C30 functional domain and symptom domain between the observation group and the control group (both P > 0.05); after treatment, the functional domain score of the observation group was higher than that of the control group, the symptom domain score was lower than that of the control group, and the differences were statistically significant (both P < 0.01). The incidence rates of skin itching, rash and diarrhea in the observation group were 23.3% (10/43), 20.9% (9/43) and 48.8% (21/43), respectively, which were higher than those in the control group [4.7% (2/43), 2.3% (1/43) and 27.9% (12/43)], and the differences were statistically significant (all P < 0.05). Conclusions:Tislelizumab combined with platinum-based drugs in advanced NSCLC patients can enhance the short-term efficacy, reduce serum tumor marker levels, and improve the immune function and quality of life of the patients, but it will increase the occurrence of skin and digestive tract adverse reactions.

Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(＞95％)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51％±0.73％to 12.04％±1.43％,indicating enhanced PD-L1 expression consistent with immunohisto-chemistry findings.Fractionated radiation(5 Gy × 3)further amplified PD-L1 upregulation(13.9％±1.54％ID/cc)compared with a single dose(11.48％±1.05％ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

In the field of healthcare service,it is crucial to optimize medical innovation services by combining the preferences of health service providers and demanders(i.e.,stakeholders).The best-worst scaling(BWS)method is a recently developed stated preference method for assessing preferences with distinctive advantages.Nevertheless,there is a lack of a comprehensive introduction to stakeholder preference assessment using BWS,thus constraining its applications and promotion.This paper introduces the process of using BWS to assess service providers'preferences for the Shared Medical Appointment for diabetes(SMART),an integrated healthcare service of medicine and health management,in the hope of providing reference for researchers for promoting the use of BWS in implementation research.

Objective To evaluate the clinical efficacy and safety of bumetanide in comparison with other diuretics for the prevention and management of postoperative pleural effusion in patients undergoing hepatobiliary surgery.Methods A total of 168 patients undergoing routine hepatobiliary surgery were randomly assigned to either the bumetanide group or the control group(other diuretics).Patients in the bumetanide group received bumetanide injection at a dose of 1 mg intravenously once daily.In contrast,the control group received one of the following treatments:furosemide injection at 20 mg intravenously once daily,furosemide tablets at 40 mg orally twice daily,or a combination of furosemide tablets(40 mg orally twice daily)and spironolactone tablets(60 mg orally twice daily).All treatments were administered for three days postoperatively.The incidence of postoperative pleural effusion,length of hospital stay,and drug-related adverse reactions were compared between the two groups.Additionally,multivariate logistic regression analysis was conducted to identify independent risk factors for moderate-to-severe pleural effusion after surgery.Results A total of 82 patients were enrolled in the bumetanide group and 86 in the control group.No significant differences were observed in the general demographic and clinical characteristics between the two groups(P>0.05),except for sex and ALT levels(P<0.05).The incidence of moderate-to-severe pleural effusion was higher in the control group than in the bumetanide group,with rates of 9.3％and 1.2％,respectively(all P<0.05).Additionally,the length of hospital stay was significantly longer in the control group(19.94±0.90 days)compared to the bumetanide group(17.15±1.06 days)(all P<0.05).Thora-centesis was performed in 2 cases in the bumetanide group and 8 cases in the control group,but this difference was not statistically significant(P>0.05).The primary adverse drug reactions in both groups included hypokalemia,hypochloremia,hyponatremia,and hypocalcemia.The overall incidence of adverse drug reactions was 35.4％in the bumetanide group and 34.9％in the control group,showing no significant difference(P>0.05).Multivariate regression analysis revealed that a history of hepatitis B,cirrhosis,and the use of bumetanide were independent predictors of moderate-to-severe pleural effusion during routine hepatobiliary surgery(all P<0.05).Conclusions Bumetanide demonstrates superior efficacy compared to other conventional diuretics in the prevention and manage-ment of postoperative pleural effusion in hepatobiliary surgery,suggesting potential clinical application value.