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.

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 influence of immune function and its changes on the prognosis of patients with sepsis. Methods 393 patients who met the diagnostic criteria of Sepsis-3 admitted to General Hospital of Southern War Zone of PLA from April 2003 to April 2017 were enrolled. Clinical data were collected and analyzed retrospectively. According to the initial immune status, patients with more than 4 days course of disease were divided into the initial immune suppression group (219 cases) and the initial immune function normal group (174 cases). According to the changes of immune function, patients with more than 7 days course of disease were divided into persistent inhibition group (113 cases), persistent normal group (96 cases), first normal inhibition group (22 cases) and first inhibited normal group (59 cases). In addition, the patients were divided into the elderly group (≥ 65 years old) and the young group (< 65 years old). Acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure assessment (SOFA), procalcitonin (PCT), C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr) within 24 hours after diagnosis of sepsis, whether respiratory failure and circulatory failure occur, hormone, immunomodulatory drugs and high-volume hemofiltration treatment within 28 days, the absolute value of lymphocyte counts for 4 consecutive days after diagnosis and 4 consecutive days before the end point event (death or survival within 28 days or more than 28 days) were collected and compared between each group. Results Among 393 sepsis patients, 174 cases had normal initial immune function, of whom 85 cases were older than 65 years old;219 cases had depression of initial immune function, of whom 118 cases were older than 65 years old. Compared with the initial immune function normal group, the levels of PCT, CRP, ALT, AST and SCr in the initial immunosuppressive group were significantly increased [PCT (μg/L): 9.32 (2.13, 34.01) vs. 4.28 (1.02, 19.02), CRP (mg/L): 89.00 (26.00, 142.00) vs. 65.25 (19.88, 119.04), ALT (mmol/L): 39.0 (39.0, 99.0) vs. 27.0 (16.2, 73.0), AST (mmol/L): 55.0 (31.0, 148.0) vs. 39.0 (23.0, 100.8), SCr (μmol/L): 132.00 (74.75, 245.00) vs. 100.25 (61.00, 182.54)], the mean absolute value of lymphocyte counts for 4 consecutive days was significantly decreased [0.615 (0.380, 0.810) vs. 1.442 (1.217, 1.742)], SOFA and APACHEⅡ were significantly increased (SOFA: 9.25±4.19 vs. 6.87±4.66, APACHEⅡ:22.27±8.96 vs. 18.25±9.47), the incidence of circulatory failure (66.2% vs. 50.0%), the incidence of respiratory failure (87.7% vs. 69.0%) and 28-day mortality (65.3% vs. 33.9%) were significantly increased, with statistically significant differences (all P < 0.05). When combined with immunosuppression, there was no significant difference in 28-day mortality between the elderly group and the young group (26.3% vs. 15.8%, P > 0.05); when the immune function was normal, the 28-day mortality of the elderly group was significantly higher than that of the young group (48.2% vs. 20.2%, P < 0.01). The 28-day mortality of the persistent inhibition group and the first normal inhibition group were significantly higher than those of the persistent normal group and the first inhibition normal group [83.2% (94/113), 81.8% (18/22) vs. 26.0% (25/96), 40.7% (24/59), all P < 0.05]. The incidence of immunosuppression in elderly patients [33.3% (14/42) vs. 10.5% (8/76)] and the incidence of persistent immunosuppression [77.0% (67/87) vs. 54.1% (46/85)] were higher than those in young patients (all P < 0.01). Conclusions Immune function is closely related to the prognosis of sepsis patients. Elderly patients with sepsis are more likely to have immunosuppression or persistent immunosuppression than young patients, and the prognosis is worse.

BACKGROUND: Osteoporosis is a serious threat to the health and quality of life in the elderly. It is important to establish an ideal experimental animal model to study the etiology and treatment of osteoporosis.OBJECTIVE: To establish a rat model of osteoporosis induced by different dosages of retinoic acid, thus selecting the optimal dosage.METHODS: Eighty female Sprague-Dawley rats were randomly divided into control, low-, middle- and high-dosage groups based on body mass (n=20 per group), The rats in the latter three groups were induced with 80, 100, and 120 mg/(kg?d) retinoic acid via gastric lavage for 14 days.RESULTS AND CONCLUSION: Compared with the control group, the bone mineral density, number of osteoblasts and osteoclasts, and bone microarchitecture in the low-dosage group showed no significant changes, while there were significant decrease in the serum level of calcium and bone mineral density of femur, significant increase in the number of osteoclasts at the femur and significant changes in the femoral microarchitecture in the middle- and high-dosage groups, especially in the middle-dose group. To conclude, 120 mg/(kg?d) retinoic acid via gastric lavage for 14 days can induce a stable osteoporosis model in rats.

ObjectiveTo explore the effects of social isolation on the cognition and expression of 5-HT2C receptor(5-HT2CR) and adenosine deaminase that act on RNA 1(ADAR1) in BALB/c mice.MethodsThe healthy BALB/c mice were isolated for 2,4,and 8 weeks individually since postnatal 21 days respectively to set up isolation mice model,the same age mice without isolation were regarded as control group.The new object location and the new object recognition tests were used to measure the spatial and non-spatial cognitive function,and western blot was used to measure the protein expression of 5-HT2CR and ADAR1.ResultsThe new object location test showed that the spatial discrimination index (DI) of BALB/c mice isolated for 2 weeks was decreased significantly compared with the control group(control group was (0.075±0.340),isolation group was (-0.653±0.308),P<0.05),and no obvious difference was found for the group isolated for 4 and 8 weeks.The new object recognition test showed that the non-spatial DI of BALB/c mice isolated for 2 and 4 weeks were decreased significantly compared with the control group(control 2 weeks group was (0.088±0.210),isolation 2 weeks group was (-0.945±0.194),P<0.05;control 4 weeks group was (0.105±0.267),isolation 4 weeks group was (-0.506±0.215),P<0.05),and no obvious difference was found for the group isolated for 8 weeks.Compared with the control group the expression of 5-HT2CR and ADAR1 in the hippocampus were decreased significantly for the group isolated for 2 weeks.(5-HT2CR:control group was (1.025±0.144),isolation group was (0.891±0.026),P<0.05.ADAR1: control group was (0.839±0.120),isolation group was (0.629±0.094),P<0.05).ConclusionsTwo week social isolation results in the decrease of spatial and non-spatial cognitive function in BALB/c mice,in the meanwhile,social isolation stress results in the obvious decrease of 5-HT2C receptor and ADAR1 protein expression in the hippocampus of BALB/c mice.

BACKGROUND:With the diversification of the choice of internal fixation for femoral intertrochanteric fracture, the fixation method for the same kind of fracture can be selected according to surgeon’s habit, and there is no unified standard. OBJECTIVE:To compare Gamma nail and proximal femoral locking plate fixation for repair of femoral intertrochanteric fractures. METHODS: A total of 94 elderly patients with unstable intertrochanteric fractures were treated in the Shanxi Armed Police Corps Hospital from April 2009 to September 2012. They were divided into two groups according to fixation methods. Gamma nail group contained 46 cases. Proximal femoral locking plate group contained 48 cases. The two fixation methods were compared and analyzed from the folowing aspects: incision length, intraoperative bleeding volume, operation time, postoperative hip function recovery, loading time and complications. RESULTS AND CONCLUSION:Incision length, intraoperative bleeding volume, loading time and complications were better in the Gamma nail group than in the proximal femoral locking plate group (P < 0.05). No significant difference in operation time was detected between the two groups (P > 0.05). The excelent and good rate of hip function was 96% (44/46) in the Gamma nail group and 92% (44/48) in the proximal femoral locking plate group at 1 year after treatment, and no significant difference was detectable between the two groups (P > 0.05). These findings suggest that Gamma nail and proximal femoral anatomic locking plate for the treatment of unstable intertrochanteric fractures can reach good recovery of hip function, but Gamma nail showed obvious advantages in incision length, intraoperative bleeding volume, loading time and complications.

BACKGROUND:Some scholars suggest that the nerve root palsy after cervical spinal stenosis treated with
decompression and implant internal fixation is related with the cervical stability and cervical lordosis, but there is controversial.
OBJECTIVE:To explore the C 5 nerve root palsy and stability after cervical spinal stenosis treated with posterior laminectomy lateral mass fixation and single-door decompression laminoplasty.
METHODS:Twenty-nine cervical spinal stenosis patients were selected and treated with posterior
decompression and implant internal fixation. Posterior laminectomy lateral mass fixation for the treatment of
cervical spinal stenosis:C3-6 lateral mass and C7 pedicel screw internal fixation was performed and caused rough surface on the facet joint;the unstable segment was confirmed according to the preoperative anteraposterior
plain film and dynamic radiographs combined with MRI and CT images, and then the corresponding segments were treated with lateral mass internal fixation, single-door decompression laminoplasty and laminoplasty.
RESULTS AND CONCLUSION:Al the 29 cervical spinal stenosis patients were fol owed-up for 8 months to 2.3 years. Among them, 14 cases were treated with posterior laminectomy lateral mass fixation, two cases had nerve root palsy in the early stage after implantation, three cases had incomplete paralysis after long-term symptom recurrence and treated with second surgery of scar remove and decompression;15 cases were treated with single-door decompression
laminoplasty, and one case had C 5 never root palsy and shoulder abduction dysfunctionafter treatment, no preoperative symptom recurrence. The nerve root palsy wil restored in 6 weeks for shortest and 9 months for longest. As the limitation of the case number, it is not clear whether there were significant differences in the correlation between C 5 nerve root
palsy and segmental stability, cervical lordosis, spinal decompression degree and the range for spinal cord shift, as wel as the nerve root palsy degree and the cervical spinal stenosis recurrence caused by forward scar between two
treatment methods, so accumulation observation of the cases and clinical experience are needed.