Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

OBJECTIVE: To explore the methods and efficacy of unilateral extra-pedicle precision puncture percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty(PKP) by digital subtraction angiography (DSA) for the treatment of osteoporotic vertebral compression fractures (OVCFs). METHODS: The clinical data of 68 patients with osteoporotic vertebral compression fractures treated from August 2015 to December 2018 were retrospectively analyzed. There were 20 males and 48 females, aged 56 to 90(73.5±8.0) years, 40 cases of double segments, 28 cases of three segments, a total of 168 vertebrae. All the patients were performed PVP orPKP through unilateral extra pedicle precision puncture under the guidance of DSA. The vertebrae were distributed in T RESULTS: All the punctures were successful in 68 patients. All the puncture needles reached the midline of vertebral body, and the bone cement was well dispersed in the vertebral body with symmetrical distribution. The operation time was 35 to 60 (41.6±3.2) minutes, and there was no puncture complications. The injection volume of bone cement was 3 to 5 (3.6±0.5) ml in each vertebra. There were 8 cases of bone cement leakage, with a leakage rate of 11.76%. All 68 patients were followed up from 12 to 27 (14.3±3.5) months in the study. VAS score and ODI at 3 days after surgery and at final follow-up time were significantly improved ( CONCLUSION PVP or PKP under the guidance of DSA via a unilateral extrapedicular approach with precision puncture can effectively relieve pain, restore vertebral body height and spinal function, which is a safe, fast and effective method in the treatment of osteoporotic vertebral compression fractures.
Angiography, Digital Subtraction ; Female ; Fractures, Compression/surgery* ; Humans ; Kyphoplasty ; Male ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Vertebroplasty

Ambystoma mexicanum/immunology* ; Amputation ; Animals ; Biomarkers/metabolism* ; Blastomeres/immunology* ; Cell Lineage/immunology* ; Connective Tissue Cells/immunology* ; Epithelial Cells/immunology* ; Forelimb ; Gene Expression ; High-Throughput Nucleotide Sequencing ; Humans ; Immunity ; Peroxiredoxins/immunology* ; Regeneration/immunology* ; Regenerative Medicine/methods* ; Single-Cell Analysis/methods*

Objective:To explore the characteristics of local brain neural activity in post stroke aphasia (PSA) patients in different frequency bands and the relationship between Western Aphasia Battery (WAB) scores and specific frequency bands. Methods:From March, 2015 to May, 2018, 15 PSA patients, and 15 healthy adults as controls matched for age, gender and education were recruited. They were assessed with WAB and scaned with resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) on the frequency bands of 0.01-0.08 Hz, 0.027-0.073 Hz, and 0.01-0.027 Hz were calculated. The ALFF and fALFF in different frequency bands were extracted and the correlation with the WAB scores in the patients were analyzed. Results:On 0.01-0.08 Hz, ALFF increased in the right precentral gyrus in the patients. On 0.027-0.073 Hz, ALFF increased values in the right precentral gyrus, and fALFF decreased in the right cerebellar Crus2 region; fALFF in the right cerebellar Crus2 region negatively correlated with the scores of information content (r = -0.576, P = 0.025), auditory comprehension (r = -0.658, P = 0.008), repetition (r = -0.616, P = 0.014) and aphasia quotient (r = -0.611, P = 0.016) of WAB. On 0.01-0.027 Hz, the fALFF decreased in the left inferior parietal limbic gyrus, and positively correlated with the scores of information content (r = 0.538, P = 0.039) and aphasia quotient (r = 0.526, P = 0.044). Conclusion:Resting-state fALFF abnormalities in PSA patients are frequency-dependent, which associate with some frequency-specific neurofunctional alterations.

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

Objective: To investigate the feasibility of transumbilical single-incision plus one port (SIPOP) robotic total mesorectal excision. Methods: Clinical data of a 70-year-old male patient with BMI 22.1 kg/m(2) who successfully underwent transumbilical single-incision plus 1 port robotic total mesorectal resection of upper rectal cancer at the General Surgery Department of Daping Hospital of Army Military Medical University on September 18, 2019 were retrospectively analyzed. Preoperative colonoscopy revealed that the distance of upper rectal cancer to anal edge was 14 cm, and the tumor size was 2.5 cm×1.5 cm×1 cm. Pathological result confirmed rectal moderately differentiated adenocarcinoma. The preoperative abdominal CT showed thickened bowel-wall of upper rectum and the blurred perirectal fat, suggesting tumor infiltration. Results: The operation was successful. There were no conversion to laparotomy or abdominal auxiliary incision, and the mesorectum of the specimen was intact. The operation time was 165 minutes, the blood loss was about 20 ml, and there were no complications such as injury to peripheral organs. Postoperative pathology showed ulcerative moderately differentiated adenocarcinoma of the upper rectum with TNM stage IVA (T4N2b). The postoperative recovery was smooth. Patient ambulated on the 1st day, the catheter was removed on the 7th day, and discharged from the hospital on the 8th day. Conclusion: The transumbilical SIPOP robotic total mesorectal excision is safe, effective and feasible.
Aged ; Humans ; Laparoscopy ; Male ; Rectal Neoplasms/surgery* ; Rectum ; Retrospective Studies ; Robotic Surgical Procedures ; Robotics ; Treatment Outcome