BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

This article outlines the formulation process of the local standard of Traditional Chinese Medicine Chronic Disease Management Guideline for Menopausal Women with Emotional Disorders(DB44/T 2547-2024;hereafter referred to as the"Guideline").By analyzing its structural framework and content,this study elucidates the TCM-specific chronic disease management strategies incorporated in the Guidelines,aiming to supply references to the development of similar standards and provide guidance for TCM chronic disease management practices.The development for the Guideline involved a multi-dimensional evidence collection process,including literature review,summary of expert experience,and expert consultations.By employing a multi-dimensional evidence-based approach,the Guideline has effectively integrated diverse evidence sources,and ensures the standard formulation being scientific and precise.The Guideline proposes the requirements for TCM-specific chronic disease management of menopausal women with emotional disorders firstly.By incorporating TCM lifestyle regulation,TCM emotional management,TCM dietary therapy,medication guidance,exercise therapies,and distinctive external treatments,the Guideline has developed into a comprehensive TCM chronic disease management system for prevention,treatment,rehabilitation and health preservation.The integrated approach effectively reduces the recurrence of emotional disorder and enhances quality of life of the patients.

Objective To investigate the effect of protocatechuic acid(PCA)on Toll-like receptor 4(TLR4)/nu-clear factor-kappa B(NF-κB)signal pathway in rats with ulcerative colitis(UC).Methods After modeling,rats were divided into control group,model group(5%trinitrobenzene sulfonic acid(TNBS)induction),low(L-PCA),middle(M-PCA),high(H-PCA)dose protocatechuic acid group(rats were given with PCA at doses of 20,40 and 80 mg/kg respectively),and intervention model group(LPS,rats were given with PCA at doses of 80 mg/kg and 0.8 mg/kg LPS solution intraperitoneally),and 12 rats in each group were given the drug continu-ously for 14 days.After treatment,rats were evaluated by disease activity index(DAI),and the morphology and apoptosis of colon were observed by hematoxylin eosin(HE)staining and TUNEL staining.The protein levels of Occludin,Zona occludens 1(ZO-1),claudin-1,Tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-10,TLR4 and p-p65/p65 in colon were detected by Western blotting.The expression of TLR4 protein in colon was de-tected by immunohistochemical staining.Results Compared with control group,the colon of model group rat showed obvious injury,DAI score and positive rate of TUNEL were increased(P＜0.05),the relative protein ex-pression of TNF-α,IL-1β,TLR4 and p-p65 were increased(P＜0.05),the relative protein expression of Occlu-din,ZO-1,claudin-1 and IL-10 were decreased(P＜0.05).Compared with model group,colonic injury was allevi-ated in L-PCA,M-PCA and H-PCA groups,DAI score and positive rate of TUNEL were decreased(P＜0.05),the relative protein expression of TNF-α,IL-1β,TLR4 and p-p65 were decreased(P＜0.05),the relative protein expression of Occludin,ZO-1,claudin-1 and IL-10 were increased(P＜0.05).Compared with H-PCA group,co-lon injury was aggravated in LPS group,DAI score and positive rate of TUNEL were increased(P＜0.05),the rel-ative protein expression of TNF-α,IL-1β,TLR4 and p-p65 was increased(P＜0.05),the relative protein expres-sion of Occludin,ZO-1,claudin-1 and IL-10 was decreased(P＜0.05).Conclusions Protocatechuic acid can al-leviate TNBS-induced colon injury in UC rats,improve intestinal barrier function,and inhibit colon inflammatory response,the mechanism of which is related to the activation of TLR4/NF-κB signaling pathway.

Objective To investigate the relationship between serum C-C motif ligand 23 (CCL23),Stanniocalcin-1 (STC1) levels and prognosis in patients with severe hypertensive intracerebral hemorrhage (HICH). Methods A total of 122 severe HICH patients who visited the Department of Neurosurgery,Hohhot First Hospital from March 2021 to March 2023 were regarded as the study subjects (HICH group),122 patients with mild HICH during the same period (mild group) and 122 healthy individuals who underwent physical examinations were considered healthy. HICH patients were separated into survival group(n=94) and death group(n=28)based on prognosis. ELISA was applied to detect serum levels of CCL23 and STC1. Spearson on method was used to analyze correlations and multivariate COX regression was used to investigate the influencing factors of prognosis in HICH patients,and ROC curve was applied to analyze the predictive value of serum CCL23 and STC1 levels for the prognosis. Kaplan-Meier was applied to analyze the relationship between serum CCL23,STC1 levels and clinical outcomes. Results Serum CCL23(53.32±10.85pg/ml,78.49±11.21pg/ml,112.47±11.53pg/ml)and STC1 (15.12±2.63ng/ml,19.07±2.58ng/ml,22.15±2.75ng/ml)levels in the healthy group,mild disease group and HICH group were increased successively,and the differences was statistically significant (F=856.967,215.043,all P<0.05). The serum levels of CCL23 (108.02±13.51pg/ml) and STC1 (21.06±3.28ng/ml) in the survival group were lower than those in the death group(127.41±13.55 pg/ml,25.83±3.23 ng/ml),the Glasgow coma (GCS) score (8.95±0.92 ) of the survival group was higher than that of the death group(7.61±0.77),and the differences were statistically significant (t=6.663,6.810,7.005,all P<0.001). The serum levels of CCL23 and STC1 were negatively correlated with GCS score (r=-0.481,-0.426,all P<0.001). CCL23[OR(95％CI):1.240(1.091～1.409)],STC[OR(95％CI):1.754(1.215～2.533)]and GCS[OR(95％CI):0.087(0.020～0.382)]score were the influencing factors for poor prognosis in HICH patients . The AUC(95％CI) of CCL23 combined STC1 in the prediction of the prognosis of HICH patients was 0.939 (0.880～0.974) which was higher than that of single diagnosis (Z=1.974,2.040,P=0.048,0.041),the sensitivity and specificity of combined diagnosis were 85.71％ and 94.68％,respectively. The 6-month follow-up survival rate of patients with high expression of CCL23 and STC1 (51.06％ vs 93.33％,56.86％ vs 91.55％) was lower than that of patients with low expression of CCL23 and STC1,and the differences were statistically signrficant (Log rank x2=34.777,23.781,all P<0.05). Conclusion The serum levels of CCL23 and STC1 are high in severe HICH patients,which are closely related to their prognosis. High expression of CCL23 and STC1 may indicate poor clinical outcomes in patients.

Objective To investigate the relationship between serum C-C motif ligand 23 (CCL23),Stanniocalcin-1 (STC1) levels and prognosis in patients with severe hypertensive intracerebral hemorrhage (HICH). Methods A total of 122 severe HICH patients who visited the Department of Neurosurgery,Hohhot First Hospital from March 2021 to March 2023 were regarded as the study subjects (HICH group),122 patients with mild HICH during the same period (mild group) and 122 healthy individuals who underwent physical examinations were considered healthy. HICH patients were separated into survival group(n=94) and death group(n=28)based on prognosis. ELISA was applied to detect serum levels of CCL23 and STC1. Spearson on method was used to analyze correlations and multivariate COX regression was used to investigate the influencing factors of prognosis in HICH patients,and ROC curve was applied to analyze the predictive value of serum CCL23 and STC1 levels for the prognosis. Kaplan-Meier was applied to analyze the relationship between serum CCL23,STC1 levels and clinical outcomes. Results Serum CCL23(53.32±10.85pg/ml,78.49±11.21pg/ml,112.47±11.53pg/ml)and STC1 (15.12±2.63ng/ml,19.07±2.58ng/ml,22.15±2.75ng/ml)levels in the healthy group,mild disease group and HICH group were increased successively,and the differences was statistically significant (F=856.967,215.043,all P<0.05). The serum levels of CCL23 (108.02±13.51pg/ml) and STC1 (21.06±3.28ng/ml) in the survival group were lower than those in the death group(127.41±13.55 pg/ml,25.83±3.23 ng/ml),the Glasgow coma (GCS) score (8.95±0.92 ) of the survival group was higher than that of the death group(7.61±0.77),and the differences were statistically significant (t=6.663,6.810,7.005,all P<0.001). The serum levels of CCL23 and STC1 were negatively correlated with GCS score (r=-0.481,-0.426,all P<0.001). CCL23[OR(95％CI):1.240(1.091～1.409)],STC[OR(95％CI):1.754(1.215～2.533)]and GCS[OR(95％CI):0.087(0.020～0.382)]score were the influencing factors for poor prognosis in HICH patients . The AUC(95％CI) of CCL23 combined STC1 in the prediction of the prognosis of HICH patients was 0.939 (0.880～0.974) which was higher than that of single diagnosis (Z=1.974,2.040,P=0.048,0.041),the sensitivity and specificity of combined diagnosis were 85.71％ and 94.68％,respectively. The 6-month follow-up survival rate of patients with high expression of CCL23 and STC1 (51.06％ vs 93.33％,56.86％ vs 91.55％) was lower than that of patients with low expression of CCL23 and STC1,and the differences were statistically signrficant (Log rank x2=34.777,23.781,all P<0.05). Conclusion The serum levels of CCL23 and STC1 are high in severe HICH patients,which are closely related to their prognosis. High expression of CCL23 and STC1 may indicate poor clinical outcomes in patients.

Esophagogastric variceal bleeding (EGVB) is one of the main complications of decompensated portal hypertension, especially in patients with liver cirrhosis, and it often has a high mortality rate. Medication combined with endoscopy is the main prevention and treatment method for EGVB, while transjugular intrahepatic portosystemic shunt (TIPS) combined with variceal embolization can also be selected for some high-risk patients, and individualized diagnosis and treatment of portal hypertension based on hepatic venous pressure gradient should become the latest consensus and the main strategy. This article mainly reviews endoscopic therapy and TIPS for the prevention and treatment of EGVB patients with decompensated portal hypertension in terms of selection of indications, incidence rate of complications, and respective advantages and disadvantages.

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 ^-5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Neoplasm, Residual/pathology* ; Biomarkers, Tumor/genetics* ; Computational Biology

Objective To investigate the potential of ginkgolide B(GB)in mitigating vascular endothelial injury by antagonizing endoplasmic reticulum stress(ERS)and elucidate its underlying molecular mechanism.Methods An injury model of human bone marrow-derived endothelial progenitor cells(EPCs)induced by tunica-mycin(TM)was established.Cell proliferation was assessed using MTS assay,while cell viability was determined through Calcein-AM/EthD-I double staining.Transwell assay was employed to evaluate cell migration ability.DCFH-DA staining was utilized to measure intracellular ROS levels,and NADPH activity was quantified via ELISA.JC-1 and DiOC6 staining were performed for qualitative and quantitative assessment of mitochondrial membrane potential respectively.Qrt-pcr analysis was conducted to determine mRNA expression levels,whereas western blot analysis enabled detection of protein expression levels in the cells.Results GB dose-dependently attenuated tunicamycin-induced ERS-mediated endothelial injury in hEPCs,as evidenced by decreased cell viability,impaired cell migration,and angiogenesis inhibition(P<0.01).Furthermore,GB treatment significantly reduced ROS production and NADPH levels within the cells(P<0.01),while also inhibiting ERS-mediated decline in mitochondrial membrane potential concentration-dependently(P<0.01).Additionally,GB inhibited the expression of ERS-related proteins such as GRP78,ATF4,CHOP etc.,regulated apoptosis-related protein Bcl-xl,Bax cleaved caspase-4 cytochrome c;thereby effectively counteracting endoplasmic reticulum stress-induced cellular damage.Conclusions GB exerts a protective effect on vascular endothelium by antagonizing endoplasmic reticulum stress;this mechanism may be attributed to its ability to reduce intracellular reactive oxygen species levels.It also suppresses the expression of ERS-related proteins(CHOP78 and ATF4),and modulates apoptosis-associated proteins(Bcl-xl,Bax,cleaved caspase-4,and cytochrome c).