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.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

ObjectiveTo develop a rehabilitation program of nature posture treatment (NPT) suspension therapy based on the International Classification of Functioning, Disability and Health-Children and Youth version (ICF-CY) framework, and apply it to neurodevelopmental disorders. MethodsThe ICF-CY theoretical group (group A) and NPT suspension therapy group (group B) were established. Group A searched literature from common databases, to extract high-frequency words related to suspension therapy and match with categories of ICF-CY, to develop ICF-CY theoretical framework of the NPT suspension therapy. Group B developed specific rehabilitation procedures and training items based on the framework to compose the training pool. A total of 110 children aged less than six years with neurodevelopmental disorders and associated motor impairments were selected from outpatient or inpatient of the First Affiliated Hospital of Xinxiang Medical University, between October, 2019 and October, 2022. They were randomly divided into control group (n = 55) and clinical group (n = 55), who received routine neurodevelopmental therapy and NPT suspension therapy program based on ICF-CY, respectively, for a week. The incidence of satisfaction, acceptance and adverse events were observed. ResultsTwo cases in the control group and four cases in the clinical group dropped down. For the clinical group, the incidence of satisfaction was 98% (50/51), with acceptance of 96% (49/51), and one adverse event occurred. For the control group, the incidence of both the satisfaction and acceptance was 100%, and no adverse event occurred. There was no significant difference in the incidence of satisfaction, acceptance and the adverse event (P > 0.05). ConclusionThe NPT suspension therapy program based on the ICF-CY framework is safe and acceptable for children with neurodevelopmental disorders.

Objective:To compare the efficacy of laparotomy and laparoscopic Glisson pedicle transecting segmental hepatectomy in the treatment of hepatocellular carcinoma.Methods:The clinical data of 138 patients with hepatocellular carcinoma who underwent Glisson pedicle transection hepatectomy in the Affiliated Hospital of Chengde Medical College from March 2012 to November 2015 were collected retrospectively. 45 patients underwent laparoscopic surgery (laparoscopic group) and 93 patients underwent laparotomy. 45 patients were selected as open group according to the most clinical ratio of propensity score. The baseline data, operation, stress index, liver function index and postoperative survival rate were compared between the two groups. COX proportional hazard regression model was used to analyze the influencing factors of 5-year prognosis. Normally distributed measurement data were expressed as mean±standard deviation ( Mean± SD), and independent sample t test was used for comparison between groups. The chi-square test was used to compare the enumeration data between groups. Results:The operation time, intraoperative blood loss, blood transfusion cases, complications, postoperative eating time, drainage tube removal time, and hospital stay in the laparoscopic group were (219.48±53.61) min, (208.53±39.74) mL, 2, 3, (3.62±0.51) d, (4.73±0.85) d, (10.59±1.37) d, the open group were (185.37±46.92) min, (267.49±35.83) mL, 8, 10, (4.56±0.73) d, (5.29±0.94) d, (13.87±1.68) d, the differences between the two groups were statistically significant ( P<0.05). Cortisol, norepinephrine, C-reactive protein, aspartate aminotransferase, alanine aminotransferase, total bilirubin in the postoperative laparoscopic group) And albumin levels were (258.39±30.76) ng/mL, (66.78±7.31) ng/mL, (28.39±3.45) μg/mL, (66.51±7.14) U/L, (73.39±7.85) U/L, (20.67±2.74) μmol/L, (37.52±6.48) g/L, the open group were (316.92±37.51) ng/mL, (75.63±8.39) ng/mL, (38.47±4.56) μg/mL, (82.39±9.06) U/L, (94.05±9.74) U/L, (22.93±3.18) μmol/L, (34.65±5.87) g/L, the differences between the two groups were statistically significant ( P<0.05). There were no statistically significant difference in overall survival rate and tumor-free survival rate between the laparotomy group and the laparoscopic group at 1, 3, and 5 years after surgery ( P>0.05). The COX proportional hazards regression model showed that HBsAg positive, Child-Pugh grade, alpha-fetoprotein, and tumor diameter were risk factors affecting the 5-year prognosis of patients ( HR=6.627, 7.518, 5.143, 4.881, 95% CI: 1.516-9.738, 2.382-12.495, 3.078-6.249, 1.925-7.723, P<0.05). Conclusion:The long-term effects of laparotomy and laparoscopic Glisson pedicle transection hepatectomy are the same in selective hepatocellular carcinoma cases, but laparoscopic surgery can reduce intraoperative blood loss, blood transfusion cases and complications, facilitate early removal of drainage tube and food intake, shorten hospital stay, reduce stress reaction, and promote the recovery of liver function, so the short-term effect is better.

Objective:To explore the clinical efficacy of posterior short-segment internal fixation for the treatment of brucella spondylitis (BS).Methods:The medical records of 34 patients with BS admitted from January 2014 to June 2019 were retrospectively analyzed. There were 22 males and 12 females; the age was 52.3±10.6 years (range 35-72 years). On the basis of standardized use of antibacterial drugs, the lumbar spine posterior short-segment internal fixation was used. Twenty-nine cases underwent simple internal fixation, and posterolateral bone graft fusion, while 5 cases underwent primary debridement, autologous bone grafting and interbody fusion. Monitor erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and test tube agglutination test (SAT) were used to assess inflammation control. Imaging examinations of patients before operation, 1 month after operation, 3 months after operation, 6 months after operation, 1 year after operation to the last follow-up were analyzed to evaluate the condition of intervertebral fusion. The clinical efficacy evaluation was based on the pain visual analog scale (VAS), Japanese Orthopaedic Association (JOA) score, modified MacNab grading, and American Spinal Injury Association (ASIA) grading, as well as surgery-related complications.Results:The operation time of 34 patients was 104.64±16.72 min (range 65-145 min), the average hospital stay was 16.49±7.41 days (range 7-38 d), and the average postoperative follow-up time was 20.2 months (range 12-34 months). At the last follow-up, the ESR and CRP fell to the normal range, and the SAT was negative. At 3 months postoperatively, 11 cases (32.35%) reached Bridwell fusion criteria of grade II, 23 cases (67.65%) of grade III; 3 cases (8.82%) of grade I fusion at 6 months after surgery, 31 cases reached grade II fusion (91.18%); all reached grade I fusion at the last follow-up. After the operation, the symptoms of the waist or lower extremities were significantly relieved. The VAS score was 6.3±1.4 before the operation, 4.1±1.2 at 1 month after the operation, 2.7±1.4 at 3 months after the operation, 1.6±1.0 at 6 months after the operation, and 1.2±0.8 at the last follow-up. The JOA score before surgery was 13.8±2.4, 1 month after surgery 17.6±2.6, 3 months after surgery 21.7±3.1, 6 months after operation 4.9±2.7, and at the last follow-up 25.7±1.8. Compared with the preoperative time nodes of the above indicators, the differences were statistically significant. At the last follow-up, of the 12 patients (2 cases of grade C, 10 cases of grade D) with preoperative neurological dysfunction, 2 cases recovered from grade C to grade D, and 10 cases recovered from grade D to E; the excellent and good rate of modified MacNab grading reached 97.06% (33/34). No extradural hematoma, nerve damage, cerebrospinal fluid leakage and other surgical complications occurred. Only 1 case had wound infection complication, and the prognosis was good after active treatment. There were no recurrences during the follow-up period.Conclusion:On the basis of standardized antimicrobial treatment, posterior lumbar short-segment internal fixation is a safe and effective method for the treatment of BS, and good clinical effects can be obtained.

Objective:This study aimed to establish an eXtreme Gradient Boosting(XGBoost) model that can predict the recurrence of hepatocellular carcinoma(HCC)patients after laparoscopic hepatectomy (LH) surgery.Methods:A total of 440 patients with primary HCC who received LH treatment for the first time from January 2013 to September 2016 in Affiliated Hospital of Chengde Medical University were selected as the research objects. The diagnosis method was pathological diagnosis. Research objects were divided into training group ( n=88) and verification group ( n=352) at a ratio of 2∶8 by random number table method. The Kaplan-Meier method was used to draw the recurrence-free survival curve, and the Log-rank test was used to compare the survival of the two groups; the training group was used to establish the COX regression model and the XGBoost model to screen independent predictors of recurrence after LH; receiver operating characteristic(ROC) curve was used to analyze the predictive abilities of the two models, and conducted internal verification in the verification group; Hosmer and Lemeshow Test was used to evaluate the calibration of the two models, and P>0.05 was used as a good fit between the model and the actual situation. Results:Both the COX regression model and the XGBoost model screened out tumor thrombus, low degree of differentiation, tumor microvascular infiltration (MVI), number of tumors, large tumors, and positive hepatitis B surface antigen were independent predictors of tumor recurrence( HR=2.477, 0.769, 1.786, 1.905, 1.544, 1.805; 95% CI: 1.465-4.251, 0.619-0.819, 1.263-2.546, 1.354-2.704, 1.272-1.816, 1.055-2.555). The XGboost model scores were 32 points, 29 points, 24 points, 18 points, 16 points, 11 points, respectively. In the training group, the area under the curve (AUC) of the COX regression model and XGBoost model for predicting recurrence were 0.746 (0.730-0.762) and 0.802 (0.785-0.818), respectively. The XGBoost model had strong predictive ability and was confirmed in the validation cohort. Conclusions:This study had established and verified the XGBoost model that can predict the recurrence of HCC patients after receiving LH for the first time. It can be used in clinics to assist doctors in formulating personalized postoperative monitoring programs for patients. Early detection, early diagnosis and early treatment of tumors and strengthening of postoperative follow-up are important measures to improve the prognosis of patients.

Objective:The clinical characteristics of patients with primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNSL-DLBCL) and the effects of different treatment schemes on their survival and prognosis were analyzed retrospectively.Methods:A total of 49 patients with PCNSL-DLBCL who presented at the Tianjin Medical University General Hospital from July 2014 to December 2020 were included, and their clinical data were retrospectively analyzed. They were divided into four groups: the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group. The median overall survival (OS) and progression-free survival (PFS) were calculated, and the survival prognosis was compared by univariate and multivariate prognostic analysis.Results:The median OS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 16.5 months, 4.5 months, 42 months, and not reached, respectively ( P<0.001) . The median PFS time of the MTX group, the R-CDOP group, the BTKi-R-MTX group, and the RLZT group was 7 months, 1.5 months, 20 months, and 5 months, respectively ( P=0.005) . Multivariate prognostic analysis showed that double expressor lymphoma, IESLG risk grade, and different treatment methods were the prognostic factors of PCNSL-DLBCL. Conclusion:The survival and prognosis of PCNSL-DLBCL are affected by different treatment schemes. The role of CD20 monoclonal antibody in the treatment of PCNSL-DLBCL is still controversial. The treatment scheme containing BTKi has great potential for PCNSL-DLBCL. RLZT scheme has a good prospect for elderly patients who cannot tolerate high-dose chemotherapy and radiotherapy.

Objective:To develop a novel α vβ 3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods:The α vβ 3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models ( n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results:177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions:177Lu-EB-RGD can target α vβ 3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

Objective To discuss the clinical and radiological features of congenital absence of the internal carotid artery.Methods Four patients of the congenital absence of the internal carotid artery were reported and the clinical and radiological features were summarized by a review of the literature.Results Four patients were shown subarachnoid hemorrhage ( SAH) , transient ischemic attack ( TIA) , epilepsy and headache, respectively.All of the four patients presented the absence of unilateral or bilateral carotid arteries in cervical computed tomography angiography ( CTA) or magnetic resonance angiography ( MRA).Carotid canal was absent in all the patients in CT base of skull and multiple intracranial vascular dysplasia was shown in all the patients.Basilar or posterior communicating artery was presented as dolichoectasia in 3 patients.There were 2 patients who suffered aneurysm.Conclusions The onset of the congenital absence of the internal carotid artery can be presented in any age.Sudden severe headache as initial symptom caused by SAH is showed more common in children and adolescents.TIA is commonly seen in the elderly.CT shows carotid canals are absent in the base of skull.Unilateral or bilateral carotid arteries are shown absent in CTA or MRA.Multiple intracranial vascular dysplasia is shown in CTA or MRA.Carotid artery CTA has been considered as the optimal imaging method of showing the congenital absence of the internal carotid artery.